Official Journal of
The Japan Society
for Biomedical Gerontology

ISSN 0912-8921

48
No.2
2024

基礎老化研究第47回日本基礎老化学会大会
2024年・6月15日（土）
・6月16日（日）
芝浦工業大学豊洲校舎（東京都江東区芝浦3丁目7-5）

プログラム・発表抄録


第 47 回

日本基礎老化学会大会
老化研究における医工連携大会長   福井浩二 芝浦工業大学システム理工学部教授
運営委員長 加藤優吾 鳥取大学医学部助教



15

-16

日本基礎老化学会 ・ Japan Society for Biomedical Gerontology

大会組織
大会長
福井

浩二

芝浦工業大学運営組織委員
委員長
加藤

優吾

鳥取大学

石井

恭正

東海大学

柳井

修一

東京都健康長寿医療センター研究所

中村朱里

芝浦工業大学岸本

鮎太

芝浦工業大学佳美

芝浦工業大学委員

事務局
野木アドバイザー
石神昭人

東京都健康長寿医療センター研究所

三浦ゆり

東京都健康長寿医療センター研究所

基礎老化研究48 巻第２号（2024 年）

日本基礎老化学会会誌
編集委員会委員長： 木村展之

岡山理科大学獣医学部〒 794-8555
編集委員会委員：

赤木

一考

富山大学

恭正

東海大学

陽子
孝

理化学研究所

修一
敬典

至学館大学

理尋

旭川医科大学〒 078-8510

藤田泰典

埼玉県和光市広沢 2 番 1 号
老化ストレス応答研究プロジェクトチーム

愛知県大府市森岡町 7 － 430

健康科学部〒 474-8651
橋本

東京都板橋区栄町 35 － 2

国立長寿医療研究センター研究所〒 474-8511

多田

加齢変容研究チーム

環境資源科学研究センター〒 351-0198
澁谷

分子生命科学神奈川県伊勢原市下糟屋 143

東京都健康長寿医療センター研究所〒 173-0015

伊藤

未病分野

富山県富山市杉谷 2630

医学部

〒 259-1193
板倉

愛媛県今治市いこいの丘 1 － 3

和漢医薬学総合研究所〒 930-0194
石井獣医保健看護学科

栄養科学科

愛知県大府市横根町名高山 55
先端医科学講座
北海道旭川市緑が丘東２条１丁目 1 番 1 号

東京都健康長寿医療センター研究所〒 173-0015

老化制御研究チーム

東京都板橋区栄町 35 － 2

BIOMEDICAL GERONTOLOGYvol. 48 No.2 2024

Official Journal of The Japan Society for Biomedical Gerontology
Editor-in Chief:

Nobuyuki Kimura Department of Veterinary Associated Science, Faculty of
Veterinary Medicine, Okayama University of Science 1-3
Ikoinooka, Imabari, Ehime 794-8555, JAPAN

Editors:

Kazutaka Akagi

Institute of Natural Medicine, University of Toyama
2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan

Takamasa Ishii

Department of Molecular Life Science Tokai University
School of Medicine
143 Shimokasuya, Isehara, Kanagawa 259-1193, JAPANYoko Itakura

Research team for Aging Science, Tokyo Metropolitan
Institute of Gerontology
35-2 Sakaecho, Itabashi-ku, Tokyo 173-0015, JAPANTakashi Ito

RIKEN Center for Sustainable Resource Science
2-1 Hirosawa, Wako, Saitama, 351-0198, JAPANShuichi Shibuya

Aging Stress Response Research Project Team, National
Center for Geriatrics and Gerontology 7-43
Morioka-cho, Obu, Aichi 474-8511, JAPANHirobumi Tada

Department of Nutrition, Faculty of Wellness, Shigakkan
University
55 Nakoyama, Yokonemachi, Obu, Aichi 474-8651,
JAPAN

Michihiro

Division of Advanced Medical Science, Asahikawa Medical

Hashimoto

University
1-1-1 Midorigaoka Higashi-2-jyo, Asahikawa, Hokkaido
078-8510, JAPANYasunori Fujita

Research Team for Functional Biogerontology, Tokyo
Metropolitan Institute of Gerontology
35-2 Sakaecho, Itabashi-ku, Tokyo, 173-0015, JAPAN【日本基礎老化学会賛助会員一覧】
下記の諸団体が賛助会員として本学会を支えています。
賛助会員は随時募集しております。事務局にお問い合わせください。
あなたの会社も老化研究を支えてみませんか？入会をお待ちしています。

賛助会員
ココロカ株式会社
小林製薬株式会社
大正製薬株式会社
東洋レヂン株式会社
日本水産株式会社（株）
ファンケル総合研究所
マルサンアイ株式会社（50 音順）

広告掲載のご案内

平素より、賛助会員として本学会の活動を支えていただき、心から感謝申し上げます。
さて、当学会では、学会運営の活性化を図るべく、会誌「基礎老化研究」の充実を進めております。
つきましては、賛助会員の皆様の広告掲載を積極的に行っていきたいと考えております。
ご協力を賜りますようお願い申し上げます。
広告掲載の要領は以下の通りとなります。
『基礎老化研究』（年３回）発行（全号掲載可）
広告原稿は doc. pdf. ppt. jpg. tif. 等のファイルで下記の事務局までメールまたは CD-R 等の媒体でお送り下さいますようお願い申し上げます。
〒 100-0003
東京都千代田区一ツ橋

1-1-1

パレスサイドビル 9F（株）毎日学術フォーラム内（委託）日本基礎老化学会事務局
TEL：03-6267-4550
FAX：03-6267-4555
E-mail：secretariat@jsbmg.jp
また、何かご質問等ございましたら、メールにてご連絡いただけますよう重ねてお願い申し上げます。
今後ともどうぞよろしくお願い申し上げます。
日本基礎老化学会事務局

この雑誌について（投稿される方へ）「基礎老化研究」（Biomedical Gerontology）は日本基礎老化学会の会誌で、基礎老化研究の振興、ならびに知識創造・統合を目的として、さらに社会一般へのアウトリーチ活動の一環として、年３回：１月（１号）、５月（２号・大会号）
、９月
（３号）に
発行される。内容は、本学会員より投稿された、または、本学会員及び編集委員会より依頼を受けた者からの巻頭言、総説（老化理論を含む）、トピックス、原著論文、随筆、書評、その他で構成される。但し、３号には基礎老化学会シンポジウムの抄録も掲載される。会員は簡易冊子体の配布を受け、かつ無料でオンライン版が学会 HP で閲覧できる。
なお、「学会員に幅広く多くの投稿を促したい」との意向を踏まえ、「自由投稿（総説・トピックス・原著論文・学会報告・海外便り・書評・ニュースコメント等）」欄を設ける。

投

稿

規

定

１．全ての原稿の採用については、編集委員会で決定する。総説、トピックス、および原著論文については、編集委員または編集委員会で依頼した審査委員による査読を行う。
２．著者による校正は、初校時に１回行う。その際に投稿内容の大幅な追加や変更は認めないものとする。
３．本誌に掲載された記事の著作権は、日本基礎老化学会に帰属する。但し、自身の著作を使用する場合には、本学会に断り無く自由に使用できる。
４．目次、総説の要旨、およびトピックスの題目は日本基礎老化学会のホームページに掲載される。発行後２年経過した
総説、トピックス等はインターネット上に無料で公開される。
５．総説、トピックス、および原著論文の著者には、該当 PDF ファイルを無料で進呈する。別刷り希望の場合は有料（実費）となるので、投稿・原稿提出時にその旨連絡すること。
６．原稿の執筆に際して、本誌の執筆要領に従うこと。

執

筆

要

領

原稿は全てワードプロセッサーを使用し、横書きで作成する（原稿はデジタルファイルで提出する）。１）第１頁には、原稿の表題、著者名、所属機関、所在地を和文と英文で、また、電話番号、FAX 番号、E-mail アドレスを記載する。著者が複数の場合は、連絡先の著者を明記する。２）第２頁にも初めに、表題、氏名を書き、その後に本文を書く。３）本文に節を設ける場合、１．、２．、３．、・・・を付けて節を示す。以下の項目は１）、２）、３）・・・、a）、b）、c）・・・とする。また、イタリック体、ギリシャ文字、記号が正しく出力されていることに注意する。原稿はテキストファイルまたは MS ワードファイル等で作成したデジタルファイルで提出する（欧語・数字は半角を用いる）。同時に提出する図・表および写真は、PDF、PPT、TIFF、JPEG 形式等のデジタルファイルで提出する。オンライン版はカラー図も受け付ける。
冊子体への印刷は原則、白黒またはグレースケールで行うが、カラー希望の場合は著者の負担とする。図表の挿入部位は本文中に示す。尚、本誌１ページは約 1,600 字に相当する。図の大きさを考慮して、全体の長さを調節すること。原稿（デジタルファイル）は E-mail に添付して送付するか、USB 記憶媒体等で送ることができる。コンピュータファイルについては、印刷所あるいは編集委員会で対応できない場合は、著者に協力を求めることがある。
１．巻頭言（展望） 刷り上がり１頁に収まるようにする。本文の長さは 1,500 字以内（タイトルと氏名を除く）。
２．総説

一つのテーマについて、専門的知識に基づき、関連する多くの研究論文を総括、解説、評価した、所謂ミニレ

ヴュー。
１）本文の長さ：図、表も含めて刷り上がりで６ページ（9,600 字）程度を基本とする。
２）題名：40 字以内とし、内容を的確に表したもので、且つ、読者の興味を引くよう工夫する。
３）要約およびキーワード：要約およびキーワード（５個以内の英語）を必ず付す。要約は日本語（400 字以内）、およびその英訳（200 words 以内）とする。
４）用語：本文中の用語はなるべく日本語にする。但し、欧語の方が一般的なもの、解りやすい場合は欧語でよい。
外国の人名は原語、地名はカタカナで表記する。
専門術語：それぞれの専門分野の用語集に従う。動植物の学名、遺伝子名などでイタリック体で印刷されるべきものについては、原稿に下線をつけるなどして区別する。
略語：初出箇所にフルタームの後に括弧で括った略語を記入する。可能なら日本語を入れる。 文体：
「である」
調とする。
数字・単位：数字はアラビア数字とし、単位は国際単位系を用いる。
５）引用文献：原稿中で引用された文献は、引用文献 と見出しをつけて、論文中に引用した順に番号をつけて表示する。本文中では該当する位置に［］で括って上付き表示する。１つの事柄に複数の論文を引用する場合

には［1,5,7］または［2-6］のように記述する。著者名を引用する場合で３名以上の連名の時は、それ以下を“ら”を用いて省略する。雑誌名は、略称（ISO 4）をもちいる。末尾文献リストは引用した順とし、記載は以下の通りとする。未発表論文、私信は末尾文献リストには加えず、本文中の該当する位置に［］で括って表示する。

１．Shimokawa I, Komatsu T, Hayashi N, et al . The life-extending effect of dietary restriction requires
Foxo3 in mice. Aging Cell 14: 707-709, 2015.
２．Roth GS, Ingram DK and Cutler RG. Primate models for dietary restriction research. In:Biological
Effects of Dietary Restriction, edited by Fishbein L. Berlin: Wiley, 1991, p. 193-204.
３．仲村賢一 , 下村－泉山七生貴 , 田久保海誉 ヒト組織の加齢に伴うテロメア短縮 . 基礎老化研究 24:72-76,
2000.
６）図、表、写真：そのまま印刷できるものに限る（手書きのものは受け付けない）。文献から引用する場合は、引用を明記すると共に、引用の許可が必要な場合には、著者の責任で許可を取っておくこと（許可証のコピーを原稿と共に提出すること）。白黒またはグレースケールが原則だが、オンライン版はカラー図も受け付ける。
７）図、写真にはタイトルと説明文を付ける。
３．トピックス

最近の話題性のある研究（または雑誌記事）の紹介。長さは刷り上がり４頁以内（1,600 - 6,400 字）。その他は総説に準じる。但し、要旨は不要である。
４．原著論文

基礎老化研究に関連するオリジナル性の高い研究論文。他誌で公表された内容は受け付けない。内容は、要約、目的、方法、結果、考察、引用文献、図表、およびその説明文からなる。その他は総説に準じる。
５．学会報告、海外便り

国内外の学術集会の紹介記事。長さは 1,600 字以内。留学などで滞在しているまたは過去に滞在していた研究室、訪問した研究施設の見聞の紹介記事。
６．書評

最近出版された書籍の紹介。1,600 字以内。

７．原稿の送付およびその他の問い合わせ、下記宛てに E-mail で。
編集委員会：editor@jsbmg.jp

第47回日本基礎老化学会大会〜 老化研究における医工連携 〜会期

2024 年６月 15 日（土）16 日（日）会場

芝浦工業大学豊洲校舎（東京都江東区豊洲３丁目 7-5）

大会長

福井

浩二

（芝浦工業大学）

目

第 47 回日本基礎老化学会大会

次

ご挨拶… ………………………………………………………………………3

開催概要………………………………………………………………………………………………………………4
交通案内および会場周辺案内図……………………………………………………………………………………5
交流棟 MAP……………………………………………………………………………………………………………6
参加者・発表者へのご案内………………………………………………………………………………………7-9
タイムテーブル…………………………………………………………………………………………………… 10
第 47 回日本基礎老化学会大会プログラム… …………………………………………………………… 11-19
発表抄録…………………………………………………………………………………………………………… 21
教育講演……………………………………………………………………………………………………… 23
医工連携シンポジウム（特別講演）… ……………………………………………………………………… 25
特別企画……………………………………………………………………………………………………… 31
日本組織培養学会とのジョイントシンポジウム…………………………………………………… 35-39
日韓合同シンポジウム………………………………………………………………………………… 41-56
一般口頭発表…………………………………………………………………………………………… 57-65
一般ポスター発表……………………………………………………………………………………… 67-75
企業シンポジウム……………………………………………………………………………………… 77-80
スポンサードセミナー………………………………………………………………………………… 81-85
賛助団体・企業…………………………………………………………………………………………………… 86

表表紙：第 47 回日本基礎老化学会大会ポスター－2－

第 47 回

日本基礎老化学会大会
ご挨拶

この度、第 47 回日本基礎老化学会大会の大会長を仰せつかりました芝浦工業大学の福井です。この度は本大会へご参加いただき誠にありがとうございます。本大会は日本老年学会を構成する７学会の１つとして年に１度学術集会を開催しています。本学会の特徴は基礎研究を中心に、理学・医学・薬学・工学など幅広い研究者が一堂に集い、老化という共通のキーワードのもとに研究成果を発表・議論しあう貴重で稀有な場だと思っています。
今年度は本学会の長い歴史で初めて芝浦工業大学豊洲キャンパスで実施させていただきます。その為、大会テーマを「老化研究における医工連携」と称し、本学生命医工学分野の教員２名（赤木

亮太

教授、渡邉

宣夫

教授）に特別講演を依頼しました。赤木先生には人間工学やスポーツ工学、渡邉先生にはモノづくりや流体力学から老化に関する講演を賜る予定です。また、教育講演には日本基礎老化学会の理事でもある東京都健康長寿医療センター研究所の遠藤昌吾先生にご講演を賜ることになりました。これ以外にも、日本組織培養学会とのジョイントシンポジウムや日韓合同シンポジウム、スポンサードセミナー、企業シンポジウムも開催予定です。優秀賞と学生優秀賞も準備しています。是非とも多数の先生方にご参加いただき、対面ならではの白熱した質疑応答
を皆様、是非ともよろしくお願いします。
最後になりますが、本学術集会を挙行するにあたり運営委員の各先生とアドバイザーとして本学会の理事長である石神昭人先生、三浦ゆり理事、協賛企業様には多大なご協力を賜りました。ここに御礼を申し上げます。

第 47 回日本基礎老化学会大会
大会長

－3－

福井

浩二

第 47 回日本基礎老化学会大会

大会長：福井開催概要

浩二（芝浦工業大学）

テーマ：老化研究における医工連携会

期：2024 年６月 15 日（土）・16 日（日）会

場：芝浦工業大学

豊洲校舎（東京都江東区豊洲 3 丁目 7-5）
受付：交流棟 6F

大講義室前

口演会場：交流棟 6F

大講義室

スポンサードセミナー：交流棟 5F
ポスター会場：交流棟 6F
参加費：

501 教室ホワイエ

事前参加登録（2024 年６月８日迄）

会

採

択

演

一般

10,000 円

13,000 円

学生

3,000 円

5,000 円

一般・学生

13,000 円

16,000 円

員

非会員

当日参加登録題：65 演題を採択しました。

一 般 口 頭 発 表：奨励賞、学生奨励賞対象口演の合計 32 演題を採択いたしました。
一般ポスター発表：一般演題 31 演題を、ポスター会場でのポスター展示と、討論時間における質疑応答・討論をしていただきます。
講

演：教育講演、医工連携シンポジウム（特別講演）、特別企画を計画しました。

シ ン ポ ジ ウ ム：大会１日目（15 日）に、日本組織培養学会とのジョイントシンポジウム・日韓合同シンポジウム・企業シンポジウムを企画しました。
問 い 合 わ せ 先：第 47 回日本基礎老化学会大会事務局
芝浦工業大学〒 337-8570

システム理工学部

生命科学科

分子細胞生物学研究室

埼玉県さいたま市見沼区大字深作 307

TEL．048-720-6033

Email：2024jsbmg@gmail.com

大会ホームページ：https://sit-mcblab.sakura.ne.jp/jsbmg47/index.html－4－交通案内および会場案内図［会場］ 芝浦工業大学豊洲校舎 交流棟６F 大講義室
（東京都江東区豊洲３丁目 7-5）

電車でのアクセス◦東京メトロ有楽町線「豊洲駅」１C
または３番出口から徒歩７分◦ゆりかもめ「豊洲駅」から徒歩９分◦ JR 京葉線「越中島駅」２番出口から徒歩 15 分
◦羽田空港、成田空港から豊洲駅行きのリムジンバス有り

交通アクセス－5－

交流棟 MAP

交流棟 MAP
⼀般⼝頭発表、⽇本組織培養学会ジョイントシンポ、医⼯連携シンポ、⽇韓シンポ、教育
講演、特別企画、企業シンポスポンサードセミナー(501 教室)(⼤講義室)

ポスター発表(⼤講義室前ホワイエ)

受付＊⼤講義室には 6 階からしか⼊室できません。

スポンサードセミナー
講師控室(401 教室)

情報交換会
カフェテリア

⽣協売店

⼊⼝＊⼟曜⽇のみ営業。⽇曜⽇は営業していません。

1－6－

参加者・発表者へのご案内【参加受付】
場所：芝浦工業大学豊洲校舎 交流棟 6F 大講義室前 受付
６月 15 日（土） ８時 30 分～
６月 16 日（日） ８時 30 分～◆

事前参加登録をお済ませの参加者
参加証はご自身で事前に印刷していただき、氏名・所属をご記入の上、当日ご持参ください。
基礎老化研究 48 巻２号（第 47 回日本基礎老化学会大会号）は、基礎老化学会会員及び事前参加登録された
非会員・学生会員の参加者に事前に送付します。
※５月 25 日以降に参加登録された方は、当日受付にて配布しますので、申込番号をお伝えください。
また、当日受付にてネームケースを配布します。

◆

当日参加登録をされる方
該当区分の当日参加費用を学会バンク経由でお支払いください。
学生の方は証明書の掲示が必要となります。
ご登録時に、参加証、基礎老化研究 48 巻２号（第 47 回日本基礎老化学会大会号）、ネームケースをお渡しし
ます。

◆

参加証
参加証はネームケースに入れ、会期中は必ずご着用ください。
再発行は原則致しませんので、各自で責任を持って管理してください。

【スポンサードセミナーについて】
基礎老化学会共催のスポンサードセミナーは、芝浦工業大学豊洲校舎 交流棟 5F 501 教室で開催します。以下の
日時に、整理券を受付にて配布します。お一人あたり一枚までで、無くなり次第終了します。
６月 15 日（土） ８：30 ～ 11：30（TIMA Tokyo 株式会社）
６月 16 日（日） ８：30 ～ 11：30（株式会社タケナカ）【口演発表者へのご案内】◆ プ レゼンテーションは、日本語または英語で作成して下さい。
◆

発 表者（共同発表者を含む）は利益相反（COI）をスライド２枚目（タイトルスライドの後）に開示してください。
形式に指定はありません。

◆

 演会場（６F・大講義室）の PC 受付に 60 分前までにお越しください。翌日のご発表データの受付も可能です。
口
データ受付終了後、ご発表の 15 分前までに会場左手前方の「次演者席」にお越しください。発表会場でのデー
タ修正はできません。予めご了承ください。

－7－

◆

メディアをご持参される場合◦データは「Microsoft Power Point（以下 PowerPoint）」にて作成してください。
◦ USB メモリーに保存して、データをご持参ください。
◦今回ご用意しておりますコンピュータの OS と対応アプリケーションは以下の通りです。
OS：Windows10

アプリケーション：PowerPoint2013/2019（2016）

Macintosh 版 PowerPoint でデータを作成された場合、Macintosh 本体をご持参ください。
スライドの比率は 16：9 を推奨しますが 4：3 でも問題ありません。
◦データ表示における不具合を避けるために、下記の OS 標準フォントをお使いください。
日本語： MS ゴシック、MSP ゴシック、MS 明朝、MSP 明朝、メイリオ、游明朝、游ゴシック
英語： Arial、Arial Black、Century、Century Gothic、Times New Roman

記号表記の場合（推奨）：Symbol など◦ビデオファイルなどスライドにリンクするファイルは、1 つのフォルダに入れてください。
Windows の場合は、Windows10 および WindowsMediaPlayer12 の初期状態に含まれるコーデックで再生できる動画ファイルをお持ちください（動画ファイル WMV または MP4 形式推奨）。音声出力も可能です。
試写の際、スタッフにお申し付けください。ビデオファイル再生時のトラブルに備え、コンピュータ本体をご持参ください。
◦ PowerPoint2013、2016 をお使いの場合、初期設定では、「発表者ツールが有効」になっています。“スライドショー”の項目で“発表者ツールを使用する”のチェックを外してください。
◦学術集会の終了後、お預かりしたデータは速やかに消去いたします。
◆

パソコンをご持参される場合◦電源アダプターを忘れずにお持ちください。
◦ iPad や Surface、その他タブレット端末については、動作の保証はできかねます。ご使用される場合、発表者の皆様の自己責任において、ご使用をお願いします。
◦ Macintosh などパソコン本体に MiniD-sub15 ピンまたは HDMI 端子がない機種をお持ちになる場合、変換アダプターを忘れずにお持ちください。事務局でのご用意はございません。
◦スクリーンセーバー、ウイルスチェック、並びに省電力設定（Macintosh の場合はホットコーナーも）はあらかじめ解除しておいてください。解除されておりませんと発表中にスクリーンセーバー等が作動してしまうことがあります。解除されていない場合、PC 受付にて設定を変更させていただきます。
◦故障などのトラブルに備えて、念のためバックアップデータをお持ちください。
◦ PC 受付にて動作確認後、ご自身で会場内左前方のオペレーター席まで PC をお持ちください。
◦発表終了後、オペレーター席にてご返却いたします。

◆

ご発表について演台上にモニター・マウス・キーボードを設置します。スライドの操作およびポインタ（マウス）の操作は発表者ご自身でお願いします。質疑応答は演台にてお願いします。

－8－

【座長へのご案内】
座長の先生はセッション開始の 15 分前までに「次座長席」にお越し下さい。各セッションの進行は座長に一任しますが、時間内での進行・終了が可能となりますようにご協力下さい。
【一般演題発表者へのご案内】◆ ポスターの掲示には横 80cm、縦 165cm のボードを使用します。上部の左角に演題番号を貼付しますので、ポスターは指定された番号のボードに掲示して下さい。
芝浦工業大学 交流棟 5 階の大講義室前ホワイエがポスター会場です。
◆

ポスターは６月 15 日の 11：45 までに掲示してください。

◆ ポ スターは 16 日の 15：00 までに撤去願います。撤去時間を過ぎて残っているポスターは、処分させていただきますのでご了承下さい。
◆

ポスターの発表日時
６月 15 日（土）：12：15 〜 13：30（自由討論）】【日本基礎老化学会奨励賞及び学生優秀発表賞（学生奨励賞）◆

日本基礎老化学会奨励賞候補、Y（40 歳以下）：25 演題
学生奨励賞候補、S（発表時、学部または修士、博士課程に在籍中の学生）：23 演題
投票用紙は、６月 15 日の受付にてお渡しします。
16 日 14：50 までに受付に設置する投票箱に投票して下さい。
奨励賞（40 歳以下）
、学生奨励賞（発表時、学部または修士、博士課程に在籍中の学生）両方への応募は可能ですが、両方の受賞対象となった場合、奨励賞を優先し授与します。
選出方法は、理事および評議員、大会長に指名された本会員による投票を行います。投票数が多かった上位
３演題に対して賞を授与します。投票者は、自身が共著者となっている演題には投票できません。

【情報交流会】
会場：芝浦工業大学

豊洲生協 （交流棟 3F）

日時：６月 15 日（土）18：30 ～ 20：30
当日参加費：3000 円 （学生・招待者を除く）※当日学会バンク経由にて受付もしておりますが、事前のお申込みをお願いします。
【学会用無線 LAN サービスについて】
希望者には当日受付において、学会用無線 LAN サービスをご提供いたします。
会場内では国立情報学研究所（NII）のサービス“eduroam”にて Wifi が使用可能です。

－9－

【タ
タイムテーブル】【タイムテーブル】
1日目

2日目

大講義室

9 00
30

501教室

開会の辞

大講義室

501教室

ホワイエ

一般口頭演題Ⅲ
9:00~10:00

一般口頭演題Ⅰ
9:10~10:10

10 00
30

ホワイエ

ポスター掲示~11:45まで

一般口頭演題Ⅱ
10:15~11:15

一般口頭演題Ⅳ
10:05~10:55

11 00
30

一般口頭演題Ⅴ
11:00~12:15

スポンサードセミナー
TIMA Tokyo株式会社
11:30~12:15

12 00
30
13 00
30

15 00
30
16 00

日本組織培養学会

特別企画

ジョイント
シンポジウム
14:35~15:35

30

第48回大会長挨拶

閉会の辞

投票用紙は 16 日 14：50 までに受付に設置する投票箱に入れてください。

日韓合同シンポジウム16:30~18:10

芝浦工業大学 3F カフェテリア

19 00
30

~15:00まで

授賞式

医工連携
シンポジウム15:45~16:25

18 00
30

ポスター撤去教育講演
15:00~15:45

30
17 00

タケナカ株式会社
12:30~13:15

一般口頭演題Ⅵ
13:20~14:35

企業シンポジウム
13:30~14:30
14 00

30

スポンサードセミナー

ポスター討議12:15~13:30

情報交流会
18:30~20:30

20 00【飲食物の持ち込みについて】
大講義室は飲食物の持ち込みは禁止です。
501 教室は飲食可能です。ホワイエは、飲料のみ可です。
－ 10 －

第 47 回 日本基礎老化学会大会
プログラム
The 47th Annual Meeting of
the Japan Society for Biomedical
Gerontology
PROGRAM６月 15 日（土）／ 15 June（Sat）
9：00 ～ 9：10

開会の辞

《大講義室》
福井

9：10 ～ 10：10

浩二（第 47 回日本基礎老化学会大会長，芝浦工業大学）

一般口頭発表Ⅰ
座長：水之江雄平（東京理科大学）
小林Ⅰ-01/ Y正樹（お茶の水女子大学）

Mixed antioxidant supplement improved the coordination ability of aged mice
Akari Nakamura（Shibaura Institute of Technology）

Ⅰ-02/ Y・S

Effects of Accumulated PARIS on Aging-related Diseases	Hiroto Fukai（Laboratory of Molecular Pathology and Metabolic Disease, Faculty of
Pharmaceutical Science, Tokyo University of Science）
Ⅰ-03/ Y・S

Effect of dietary protein ratio on lipid metabolism in the mouse liver	Jialin Chen（Molecular Regulation of Aging, Tokyo Metropolitan Institute for Geriatrics andGerontology, Tokyo Biotechnology Technical School）
Ⅰ-04/ Y・S	Systemic and focal effects of the mitochondrial stress-induced mitokine GDF15 in the
adipose tissue	Tomoyoshi Fukuoh（Laboratory of Molecular Pathology and Metabolic Disease, Facility of
Pharmaceutical Science, Tokyo University of Science）
Ⅰ-05/ Y・S	Investigation of renal injury models with different concentrations of adenine	Shunki Otomo（Graduate School of System Engineering and Science, Shibaura Institute ofTechnology）
10：10 ～ 10：15

休憩

10：15 ～ 11：15

一般口頭発表Ⅱ座長：内田
嶋本

さえ（東京都健康長寿医療センター研究所）
顕（山口東京理科大学）

Ⅱ-01/ Y・S	MIPEP regulates adipocyte differentiation by maintaining the quantity and quality of
mitochondria
	Mamiko Ishimatsu（Department of Pharmaceutical Science, Graduate School of
Pharmaceutical, Tokyo University of Science）
Ⅱ-02/ S	A novel type of astrocytes expressing Olig2 in mouse dentate gyrus and their response tointermittent hypoxia
Shoichiro Omura（Department of Histology and Neuroanatomy, Tokyo Medical University）
Ⅱ-03/ Y・S	System xc-/xCT in microglia is a regulator of neuropsychiatric disorder in vitamin E
deficient mice
Hidetoshi Nagamine（Tottori University）
Ⅱ-04/ S	Co-expression of POMC and Prox1 delineates newly generated POMC neurons in the
hypothalamus through lifetime
Rina Ogawa（Department of Histology and Neuroanatomy, Tokyo Medical University）
Ⅱ-05/ S	Cerebral blood flow responses to trigeminal olfactory stimulation and its nicotinic
cholinergic regulation	Daichi Morihara（Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo
University of Agriculture and Technology）－ 12 －

11：15 ～ 11：30

移動《501 教室》
11：30 ～ 12：15

スポンサードセミナー（TIMA Tokyo 株式会社）「老化治療の最前線」
講師：犬房春彦（岐阜大学科学研究基盤センター 共同研究講座 抗酸化研究部門 特任教授）
座長：福井

浩二（芝浦工業大学）《ホワイエ》
12：15 ～ 13：30

ポスター討議（タイトルについては P18 ～ 19 に掲載）

《大講義室》
13：30 ～ 14：30

企業シンポジウム
座長：中川柳井久子（雪印メグミルク株式会社）
修一（東京都健康長寿医療センター研究所）

1．The effectiveness of Lactic Acid Bacteria for“Health Aging”
Hisako Nakagawa（MEGMILK SNOW BRAND Co., Ltd）
2．Electron Spin Resonance（ESR），Instrument for detecting radicals
Yumi Nakai（JEOL Ltd）
3．Rare sugar ～ Potential for healthy aging ～Akane Kanasaki（Matsutani Chemical Industry Co., Ltd）
14：30 ～ 14：35

休憩

14：35 ～ 15：35

日本組織培養学会とのジョイントシンポジウム
座長：片岡
中村

健（岡山理科大学）
庸輝（広島大学）

1．Innovative Gravity-Driven and Electric-Assisted Microfluidic Culture System for Human Induced
Pluripotent Stem Cell Assays
Kiyoshi Ohnuma（Nagaoka University of Technology）
2．Development of cell self-aggregation technique-based tissue engineering.
-Challenges for applications in regenerative medicine and 3D culture modelsRyosuke Iwai（Okayama University of Science）
3．Acute brain slice preparations for approaching cellular and molecular mechanisms of higher brain
function
Sho Kakizawa（Tokyo Metropolitan Institute for Geriatrics and Gerontology）
4．Microglial xCT is a novel therapeutic target for Alzheimer’s disease/ Y
Yugo Kato（Tottori University）－ 13 －

15：35 ～ 15：45

休憩

15：45 ～ 16：25

医工連携シンポジウム
座長：福井浩二（芝浦工業大学）

特別講演Ⅰ：「関節運動の絶対的な強さから瞬間的な強さへのシフト ―高齢者の姿勢制御能力向上に向けた取り組み―」
講師：赤木亮太（芝浦工業大学教授）

特別講演Ⅱ：「赤血球が流れから受ける物理刺激・機械的損傷・膜酸化現象・Aging との関連性」
講師：渡邊
16：25 ～ 16：30

休憩

16：30 ～ 18：10

日韓合同シンポジウム／ Japan-Korea Joint Symposium
座長／Chairs： 柿澤昌

宣夫（芝浦工業大学教授）（東京都健康長寿医療センター研究所）

Cheol-Koo Lee（Korea University）
1．Genomic approach to identify the role of DNA repair in longevity using genomic databases
Young Rok Seo（Department of Life Science, Institute of Environmental Medicine, Dongguk University）
2．Adverse Effects of Environmental Pollutants on Neural Stem Cells and Adult Hippocampal Neurogenesis
Jaewon Lee（Department of Pharmacy, College of Pharmacy, Pusan National University）
3．Suppression of neutrophil mitigates acute aortic dissection in H2-inhalation therapy
Masumi Iketani（Biol. Process Aging, TMIG）
4．Lifespan extender rapamycin and TOR genetics in budding yeast cells
Cheol-Koo Lee（Korea University, Seoul）
5．Effects of resistance training on fibro-adipogenic progenitors in aging skeletal muscle
Yung-Li Hung（Japan Society for the Promotion of Sciences, Juntendo University）
6．The aging process is an evolutionary phenomenon from the tumor’s perspective
Tae Jun Park（Department of Biochemistry and Molecular Biology, Ajou University School of Medicine）
7．Changes of nucleocytoplasmic trafficking in cellular senescence
Young-Sam Lee（Department of New Biology, DGIST）
8．Changes in mitochondrial fusion and fission-related gene and protein expression in AD transgenic mice/ Y・S
Anna Seino（Times Graduate School of System Engineering and Science, Shibaura Institute of Technology）《豊洲カフェテリア：交流棟 3F》
18：30 ～ 20：30

情報交流会／Banquet－ 14 －

6 月 16 日（日）／ 16 June（Sun）
9：00 ～ 10：00

一般口頭発表Ⅲ《大講義室》
座長：丸山光夫（国立長寿医療研究センター）

清水孝彦（国立長寿医療研究センター）

Ⅲ -01/ S	HIF-1α activation by fatty acid bound to 1albumin induces cell proliferation and senescencein renal proximal tubular epithelial cells
Mio Narita（Graduate School of Medical Science, Kitasato University）
Ⅲ -02/ Y	Role of plas1ma membrane phospholipid in cellular senescence	Kaori Kanemaru（Department of Applied Biological Science, Faculty of Science andTechnology, Tokyo University of Science）
Ⅲ -03/ Y・S

DNA damage induction by exosomes secreted from senescent cells
Yukihiro Ikegaki（Department Biology, Graduate School of Science）

Ⅲ -04/ Y	The Impact of senescent cells on the process of lung regeneration： possible involvement of
a nuclear receptor signaling	Mikako Hirose（Molecular and Cellular Aging, Tokyo Metropolitan Institute for Geriatrics
and Gerontology）
Ⅲ -05/ S

Molecular basis of cellular senescence triggered by CDK inhibition
Yuto Matsuo（Tokyo University of Science）

10：15 ～ 10：20

休憩

10：05 ～ 10：55

一般口頭発表Ⅳ座長：三浦木村ゆり（東京都健康長寿医療センター研究所）
展之（岡山理科大学）

Ⅳ -01/ Y	Comprehensive analysis of age-related changes in transcriptome diversity by single cell
RNA-seq data analysis
Daigo Okada（Center for Genomic Medicine, Graduate School of Medicine, Kyoto University）
Ⅳ -02/ Y・S	Lysine Specific Demethylase 1（LSD1）suppresses cellular senescence by epigeneticallyregulating Sirtuin-4 in a riboflavin uptake-dependent manner
Taiichi Osumi（Department of Biology, Graduate School of Science, Kobe University）
Ⅳ -03/ Y・S

Effect of vitamin C deficiency on age-associated genes in mouse liver	Yukari Mitsumaru（Molecular Regulation of Aging, Tokyo Metropolitan Institute for
Geriatrics and Gerontology, Department of Systems Engineering and Science, Shibaura
Institute of Technology）
Ⅳ -04/ Y・S

Effects of vitamin C on epigenetic modifications in C2C12 cells

	Tatsuki Minowa（Molecular Regulation of Aging, Tokyo Metropolitan Institute for Geriatrics
and Gerontology, Department of Biological Sciences, Tokyo Metropolitan University）
10：55 ～ 11：00

休憩－ 15 －

11：00 ～ 12：15

一般口頭発表Ⅴ座長：町田小野修一（順天堂大学）悠介（熊本大学）

Ⅴ -01/ Y・S	The impairment of chronic oxidative stress-induced autophagy causes sarcopenia withindividual atrophy in mice	Rikuto Toda（Department of Applied Physics and Chemistry, School of Engineering, Tokai
University）
Ⅴ -02/ Y

Hox based positional identities influence myogenesis in adult skeletal muscle

	Ryosuke Okino（Muscle Biology Laboratory, Tokyo Metropolitan Institute for Geriatrics andGerontology）
Ⅴ -03/ S

Effects of aging and sex on ribosome biogenesis in the skeletal muscle
Shota Fusen（Graduate School of Health and Sports Science, Juntendo University）

Ⅴ -04/ Y	Analysis of aged mice-specific abnormal muscle fibers reveals new insights into molecularmechanisms of sarcopenia
	Naoki Ito（Brain-Skeletal Muscle Connection in Aging Project Team, Geroscience ResearchCenter, National Center for Geriatrics and Gerontology）
Ⅴ -05/ Y・S

Effects of AGEs on cellular senescence in C2C12 skeletal muscle cells
Ryota Iyama（Graduate School of Human and Environmental Studies, Kyoto University）

12：15 ～ 12：30

移動《501 教室》
12：30 ～ 13：15

スポンサードセミナー（株式会社タケナカ）「産学連携における室戸海洋深層水の利用促進に向けた取り組み」
講師：福井

浩二（芝浦工業大学 システム理工学部 生命科学科 分子細胞生物学研究室 教授）
座長：加藤

13：15 ～ 13：20

休憩

13：20 ～ 14：35

一般口頭発表Ⅵ
座長：大澤
石井優吾（鳥取大学）

郁朗（東京都健康長寿医療センター研究所）
恭正（東海大学）

Ⅵ -01/ Y・S	Hydrogen rich water-induced thinning of mucus layer with changes of bacterial flora in thesmall intestine	Yui Ueta（Biological Process Aging, Tokyo Metropolitan Institute for Geriatrics andGerontology, Graduate School Life Science, Toyo University）
Ⅵ -02/ Y・S	Enhancement effect of exercise training in mice treated with deep-sea water extract-added
water-treated mice	Nagisa Tomioka（Graduate School of System Engineering and Science, Shibaura Institute ofTechnology）
Ⅵ -03/ Y

Effects of glucosamine on human colonic microbiota in an in vitro model
Tomoya Shintani（Kobe University）

Ⅵ -04/ Y・S

The Effects of Tocotrienols on Mice Pre-Fed on a High-Fat Diet	Shuntaro Richard Kashiwaya（Graduate School of System Engineering and Science, Shibaura
Institute of Technology）－ 16 －

Ⅵ -05/ Y・S

The effects of royal jelly on stem cell aging
Yukie Kande（Shiga University of Medical Science）

Ⅵ -06/ Y

Senomrphic effect of royal jelly in epidermal keratinocyte
Yukie Nakagawa（Yamada Bee Company, Inc.）

14：35 ～ 14：40

休憩

14：40 ～ 15：00

特別企画「An overview： the Past, Present, and Future of Aging Research" in Korean aging meeting」
講師：Yu Byung Pal（University of Texas Health Science Center）
座長：樋上
15：00 ～ 15：45

賀一（東京理科大学）

教育講演「若い研究者たちへ ―私の研究の黒歴史を話すよ―」講師：遠藤昌吾（東京都健康長寿医療センター研究所 研究部長）

座長：石神
15：45 ～ 16：00

授賞式

16：00 ～ 16：05

理事長挨拶
石神

16：05 ～ 16：10

昭人（日本基礎老化学会 理事長、東京都健康長寿医療センター研究所 副所長）

次回大会長挨拶堀田

16：10 ～ 16：15

昭人（東京都健康長寿医療センター研究所）

晴美（第 48 回日本基礎老化学会大会 大会長、東京都健康長寿医療センター研究所）

閉会の辞
福井

浩二（第 47 回日本基礎老化学会大会 大会長、芝浦工業大学）－ 17 －

６月 15 日（土）12：15 ～ 13：30 ／ 15（Sat）June 12：15 ～ 13：30《ホワイエ》 ポスター発表会場
P-1．Age-related changes in the muscle characteristics of forelimb and hindlimb of senescence accelerated
mouse P8 and R1 strains
Keiko Odera（Department of Biochemistry, Faculty of Pharmaceutical Sciences, Toho University）
P-2．Age-related changes of Tau in cat brain
Nobuyuki Kimura（Department of Veterinary Associated Science, Faculty of Veterinary Medicine,
Okayama University of Science（OUS））
P-3．Renal function in aged C57BL/6J mice. Age-related apolipoprotein A-II amyloid deposition impaired
the function independently of kidney aging
Hiroki Miyahara（Shinshu University）
P-4．Assessment of chronological aging and longevity intervention in healthy dogs
Takashi Ito（RIKEN CSRS）
P-5．Why do mice fed egg only diet live healthy?
Nishio Naomi（Department of school health, Faculty of Education, Saitama University）
P-6．Role of hippocampal microglia in anxiodepressive-like behaviors of aged mice
Yoki Nakamura（Department of Pharmacology, Hiroshima University）
P-7．Regular voluntary exercise increases NAD+ levels and cognitive function in aged mice
Jimmy Kim（Department of Physiology, Graduate School of Health and Sports Science, Juntendo
University）
P-8．Muscle-Derived Seno-Suppressor：Unraveling the Novel Link to Exercise Therapy
Hiromichi Tsushima（Tokyo Metropolitan Institute for Geriatrics and Gerontology）
P-9．Development of a fluorescent GABA sensor for drug discovery
Kenji Takikawa（Tokyo Metropolitan Institute of Gerontology）
P-10．Characterization of senescent cells derived from human fetal fibroblasts with defective oxidative
phosphorylation
Yasunori Fujita（Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology）
P-11．Contribution of sympathetic nerve activity on skeletal muscle contractility in young and aged rats
Harumi Hotta（Department of Autonomic Neuroscience, Tokyo Metropolitan Institute for Geriatrics andGerontology）
P-12．Effect of a traditional Japanese herbal medicine, Ninjin’yoeito, on static and dynamic changes incerebral cortical arteriolar diameters
Nobuhiro Watanabe（Department of Autonomic Neuroscience, Tokyo Metropolitan Institute for Geriatrics
and Gerontology）
P-13．Age-related impacts of the defective programmed cell death pathway on longevity in C. elegans
Sumino Yanase（Daito Bunka University School of Sports & Health Science）
P-14．Application of senescent cell removal model mice（tdTomato/human HBEGF knock-in mice）as a tool
for aging research
Mitsuo Maruyama（National Center for Geriatrics and Gerontology, Nagoya University Graduate School of
Medicine）
P-15．Diversity of SASP factors and their physiological roles in cellular senescence process
Yoichiro Kawabe（National Center for Geriatrics and Gerontology）
P-16．The relationship between ROS-induced neurite degeneration, disruption of intracellular Ca2+
homeostasis and mitochondrial dynamics
Koji Fukui（Shibaura Institute of Technology）－ 18 －

P-17．Milk derived sialylglycopeptide concentration induce BDNF production in SH-SY5Y neuroblastoma
cells.
Hisako Nakagawa（Milk Science Research Institute, MEGMILK SNOW BRAND Co. Ltd.）
P-18．Inhibitory effect of H2-inhalation on thrombolytic tPA-induced hemorrhagic transformation of
cerebral infarction
Kennosuke Sato（Biological Process Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology,
Life Science, Toyo University）
P-19．Induction of tissue-specific premature stem cell aging promotes senescence-like deterioration inremote organs
Hayato Kaneda（Shiga University of Medical Science）
P-20．Effect of basal forebrain stimulation on extracellular acetylcholine release and regional blood flow inthe piriform cortex
Jura Moriya（Department of Autonomic Neuroscience, Tokyo Metropolitan Institute for Geriatrics andGerontology, Tokyo University of Agriculture and Technology）
P-21．Analysis of Selective mRNA Splicing in Adipose tissue following Caloric Restriction
Yuhei Mizunoe（Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical
Science, Tokyo University of Science）
P-22．MMP-2 regulation improves age-related skin pathologies caused by oxidative stressShuichi Shibuya（Aging Stress Response Research Project Team, National Center for Geriatrics andGerontology）
P-23．Study of skeletal muscle aging using human iPS cells
Makoto Shimizu（Graduate School of Humanities and Sciences, Ochanomizu University, Graduate Schoolof Agricultural Sciences, The University of Tokyo）
P-24．Assessment of physical and cognitive decline in aging mouse model
Shuichi Yanai（Tokyo Metropolitan Institute for Geriatrics and Gerontology）
P-25．Age-associated changes in the amount of nucleotide sugars in mouse tissues
Rieko Imae（Molecular Glycobiology, Tokyo Metropolitan Institute for Geriatrics and Gerontology）
P-26．Age-related changes in the N-glycan expression of mouse lung
Keiko Akasaka-Manya（Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo
Metropolitan Institute of Gerontology）
P-27．Change of fucosylated N-glycans in plasma proteins from semi-supercentenarians
Hiroki Tsumoto（Tokyo Metropolitan Institute for Geriatrics and Gerontology）
P-28．A transcriptomic atlas of the adult mouse skeletal muscle and satellite cells: toward understanding
age-related sarcopenia
Yuuki Gouda（Muscle Biology Laboratory, Tokyo Metropolitan Institute for Geriatrics and Gerontology）
P-29．Approaches for Identifying of Active Substances in Hypochlorous Acid-Based Disinfectants:
Application of Absorption Spectrophotometry and Iodometry
Yuta Okada（Graduate School of System Engineering and Science, Shibaura Institute of Technology）
P-30．The comparison of dissolved components, effective chlorine concentration and free chlorine
concentration between electrolyzed and non-electrolyzed hypochlorous acid water
Kenta Sugiyama（Graduate School of System Engineering and Science, Shibaura Institute of Technology）
P-31．Analysis of sodium chlorite and acidified sodium chlorite by various measurement methods
Ayuta Kishimoto（Graduate School of Functional Control Systems, Shibaura Institute of Technology）－ 19 －

第 47 回

日本基礎老化学会大会
発表抄録

教育講演
医工連携シンポジウム（特別講演）
特別企画
日本組織培養学会とのジョイントシンポジウム
日韓合同シンポジウム
一般発表（口頭，ポスター）
企業シンポジウム
スポンサードセミナー

The 47th Annual Meeting of
the Japan Society for Biomedical
Gerontology ABSTRACTS
Educational Lecture
Collaboration with Biomedical Engineering SymposiumSpecial Program
JSBMG-JTCA Joint Symposium
Japan-Korea Joint Symposium
General Presentations（Oral and Poster Presentations）
Sponsored Symposium
Sponsored Seminar

〈教育講演〉

６月 16 日（日）15：00 ～ 15：45

若い研究者たちへ ―私の研究の黒歴史を話すよ―
講師：遠藤

昌吾

（東京都健康長寿医療センター研究所 研究部長）

座長：石神昭人（東京都健康長寿医療センター研究所）

「若い研究者たちへ ―私の研究の黒歴史を話すよ―」遠藤省吾

東京都健康長寿医療センター研究所 研究部長
老化脳神経科学研究チーム

シニアの講演といえば、「こんな研究をしてきたんだぜー！すごいだろう！」というにおいがプンプンする。そんな講演私にはできない。だって黒歴史だらけだから。若い人向けに、私の黒い歴史を主題にして、スパイスとして研究を加えて話したい。
私の黒歴史は、大学の講座の選択からはじまる。私は微生物の酸化還元酵素の研究を選んだ。当時形態や生育条件などで細菌が分類されていたが、最近の rRNA の解析により再分類が行われ、私が覚えた分類は全く役に立たない（黒歴史１）。
そんな私の数々の黒歴史、忘れたいもの、そしてそこからわずかに得られたものについて話してみたい。
そして、
私の黒歴史を聞いて、研究世界で生きる現在の若い研究者たちが「俺の方がまだましだな」と思ってもらえればと思う。

学歴：
1983 年

北海道大学薬学部卒業・薬学士（札幌市）

1985 年

同大大学院薬学研究科修士課程修了・薬学修士

1988 年

同大大学院薬学研究科博士課程修了・薬学博士

職歴：1988 年

日本学術振興会特別研究員（北海道大学薬学部、～ 1989）

1989 年

テキサス大学医学部（テキサス州ヒューストン）、博士研究員

1991 年

デューク大学薬理学（ノースキャロライナ州デューラム）、博士研究員

1995 年

ヒューストン大学生物学（テキサス州ヒューストン）、Research Assistant Professor

1997 年

理化学研究所・脳科学総合研究センター（埼玉県和光市）、研究員

2000 年

同上、ユニットリーダー（～ 2004）

2004 年

沖縄大学院大学先行研究プロジェクト（沖縄県うるま市）、代表研究者（～ 2009）2004 年

琉球大学医学部（沖縄県西原町）、客員教授（兼任、～ 2009）2009 年

東京都健康長寿医療センター研究所（東京都板橋区）、研究部長（～ 2013）2010 年

東京農工大学農学府（東京都府中市）、客員教授（兼任、～ 2020）2013 年

東京都健康長寿医療センター研究所（東京都板橋区）、チームリーダー・研究部長（～現在）

2019 年

芝浦工業大学システム理工学部（埼玉県さいたま市）、客員教授（兼任、～ 2022）－ 24 －

〈医工連携シンポジウム〉
６月 15 日（土） 15：45 ～ 16：25
老化研究における医工連携
座長：福井浩二（芝浦工業大学）

芝浦工業大学では 2008 年に生命科学科を開設した。学科全体のキーワードは「老化」である。老化に関し、
分子生物学・分析化学・有機化学・分析化学などウェットを中心として取り組む「生命科学コース」と、リ
ハビリテーション学・生体計測学・流体力学・プログラミング・モノづくりなどハードを中心として取り組
む「生命医工学コース」に分かれており、生体の内外から「老化」研究に取り組んでいる。また、2026 年
度には組織改編を予定、新たに「スポーツ健康科学コース」を創設し、学年あたりの定員は 180 名となり更なる老化研究の発展が見込まれている。本学は工学系の単科大学で、建学の精神が「社会に学び社会に貢献する技術者の育成」となっており、モノづくりの精神を長く受け継いでいる。2027 年には 100 周年を迎え、今後、様々なイベントを実施する予定となっている。
この度、「第 47 回

日本基礎老化学会大会」を芝浦工業大学という工科大学で実施することを鑑み、特別シンポジウムとして「老化研究における医工連携」を実施することとした。そこで、本学生命科学科生命医工学コースの教授２名に特別講演を依頼した。赤木亮太教授からはスポーツ科学・人間工学の分野から、高齢者の姿勢制御に関する講演を、渡邉宣夫教授からは流体力学・細胞工学の分野から、老化赤血球の診断技
術に関する講演を頂戴する。本シンポジウムが学会員の皆様にとって有益な時間となれば幸いである。
（文責：福井浩二）

特別講演Ⅰ

関節運動の絶対的な強さから瞬間的な強さへのシフト―高齢者の姿勢制御能力向上に向けた取り組み―
講師：赤木亮太（芝浦工業大学 教授）
特別講演Ⅱ

赤血球が流れから受ける物理刺激・機械的損傷・膜酸化現象・Aging との関連性
講師：渡邊宣夫（芝浦工業大学 教授）

関節運動の絶対的な強さから瞬間的な強さへのシフト―高齢者の姿勢制御能力向上に向けた取り組み―赤木亮太

芝浦工業大学 システム理工学部 生命科学科 生体機械学研究室 教授

高齢者の 1/3 は、加齢による運動機能の衰えに起因して、１年間に１回以上転倒し、重大な怪我や死、
うつ病や生活の質の低下が誘発されている。世界に先駆け、超高齢社会に突入した我が国でも、要支援・要介護認定の高齢者が急増しており（2000 年：218 万人→ 2018 年：645 万人）、高齢者の転倒リスクを低減することが喫緊の課題となっている。
歩行中の転倒リスク低減に向け、歩行中の状況把握（例：段差で躓く／強い風に煽られバランスを崩す可能性の把握）により転倒を回避するための研究が、認知・記憶機能の面から進められている。しかし、転倒の危険に晒される状況を未然に察知できない場面も多く存在する（例：夜道で歩道の凍結が判別できない／人や物に遮られ足元が見えない）。それ故、歩行中に実際に転倒しかけた際に、如何にして転倒を防ぐのか？は、転倒リスクを低減する上で重要な「問い」となる。その「答え」として、瞬時に適切な姿勢に戻し、自身の体を支える能力を高めることを想定し、現在研究を進めている。
姿勢制御に関する研究は、歩行よりも簡便な、静止立位を対象に発展してきた。従来、静止立位時の姿勢制御には関節運動の絶対的な強さ（最大関節トルク）が重要で、当該強さの決定要因となる骨格筋の量が、立位時の姿勢制御能力の決定要因でもあると考えられていた。しかし、筋収縮の開始から最大関節トルクに達するまでに 0.3 秒以上要することから、発表者は関節運動の瞬間的な強さ（短時間での関節トルクの増加率）が静止立位時の姿勢制御により重要であると考え、高齢者を対象に横断的に、トレーニング介入により縦断的に実証した。この考え方は他グループからも支持されており、静止立位時のみ
ならず、歩行時の姿勢制御能力に対しても、関節運動の絶対的な強さではなく、瞬間的な強さが重要であることが常識となりつつある。
本講演では、このような、姿勢制御に関連する評価指標としての、関節運動の絶対的な強さから瞬間的な強さへのシフトについて、発表者自身の先行研究を使いながら概説する。併せて、現在実施している、
適応的歩行評価に関する説明を交えながら、今後の取り組みについて簡単にお話ししたい。
［紹介予定の参考文献］
Akagi et al., Age Ageing , 38：564-569, 2009.
Akagi et al., Eur J Appl Physiol , 108：689-694, 2010.
Akagi et al., Eur J Sport Sci , 11：277-282, 2011.
Ema et al., AGE（Dordr），38：475-483, 2016.
Kobayashi et al., Int J Sports Med , 37：470-475, 2016.
Ema et al., J Appl Physiol（1985），123：424-433, 2017.
Akagi et al., Arch Gerontol Geriatr , 75：185-190, 2018.
Hirata et al., J Physiol Anthropol , 41：10, 2022.
Hirata et al., Eur J Appl Physiol , 122：2271-2281, 2022.

－ 26 －

2000 年４月〜 2004 年３月
早稲田大学 理工学部 機械工学科
ロボットの腕の動かしやすさの定量化をテーマに、菅野重樹研究室にて、人間共存ロボット“TWENDY-ONE”の研究・開発に携わった。
2004 年 4 月〜 2006 年３月
早稲田大学大学院 人間科学研究科 修士課程
2006 年 4 月〜 2009 年３月
早稲田大学大学院 スポーツ科学研究科 博士後期課程
2008 年４月〜 2009 年３月
日本学術振興会特別研究員（DC2：早稲田大学）
2009 年 4 月〜 2010 年３月
日本学術振興会特別研究員（PD：早稲田大学）
Muscle mechanics・Biomechanics を専門とした研究グループ（福永哲夫研究室・川上泰雄研究室・矢内利政研究室）にて、骨格筋の機能・形状・量の実測データに基づいた、ヒトの身体運動の最適化に向けた研究を進めてきた。その過程で、高齢者の骨格筋関連の実測データの取得にも励んだ。
2010 年４月〜 2013 年３月
国立スポーツ科学センター 契約研究員
日本のトップアスリートを科学的にサポートしつつ、主に骨格筋のコンディショニングに関する研究に従事していた。世界的に見ても早い段階で、超音波診断装置を用いて骨格筋の硬さを定量化する手法を導入し、コンディショニング評価への活用に挑戦していた。自身がサポートしていた競技・種目の内、女子サッカー・女子バレーボールは、ロンドン五輪でメダルを獲得した。
2013 年４月〜現在
芝浦工業大学システム理工学部生命科学科（助教：2013 年４月～ 2017 年３月、准教授：2017 年４月～ 2022 年３月、教授：2022 年４月～現在）
スポーツ科学をベースに、生活の質の改善に資するトレーニング／ストレッチング手法の提案、アスリートの傷害予防策の考案、トレーニングをサポートするシステムの開発、スポーツ動作の解析、高齢者の転倒予防策の考案などを進めている。近年では、脳機能・認知機能に視覚を絡めた研究にも着手している。

－ 27 －

赤血球が流れから受ける物理刺激・機械的損傷・膜酸化現象・Aging との関連性
渡邉宣夫

芝浦工業大学 システム理工学部 生命科学科 バイオ流体科学研究室 教授

本研究室では、血液細胞・血流・心臓血管系を対象とし、その生理的機能の未解明な観点や今日の血液循環デバイス利用に伴う血液損傷・血液凝固などのリスクイベントの発生メカニズムに着目した研究に取り組んでいる。その研究手法として、物理条件を工学的に再現した環境におく手法を主に用い、とりわけ流れの物理条件としてせん断応力に着目している。これは血液細胞にとっては変形を誘発される刺激となるわけであるが、流体の塊に対しては場所あたりの速度変化が流体塊の変形を強制する結果、微視的に見た細胞は引き裂かれるような刺激を受ける事となる。このせん断刺激に対する赤血球のＮＯ産生反応は、
入力せん断とその作用時間に応じて単純増加する事が我々の研究の結果、明らかになった（JT.
Horobin et al. Clin. Hemorheol. Microcirc. 2019. 71（2）；203-214.）。この解釈として、赤血球自身の変形能を一時的に高める効果や、近傍の内皮細胞の外側の平滑筋細胞の血管弛緩作用を促す事で（血管）流路そのものの通り道を広げる事につながり、一種の防衛反応とも考えらえる。このように生体内の血流下条件では優れたシステムとしての調節機構が成立している。その一方で、重症な呼吸器患者や心不全患者を治療・延命療法する膜型人工肺や血液ポンプなどの血液循環デバイスの利用は、さらに高いせん断応力の発生を促すため、ひとたびその細胞防衛能力を超越したせん断応力が作用してしまえば、赤血球の損傷、その変形能の低下さらには細胞破壊（溶血）による血漿への遊離ヘモグロビン流出、血液循環全体で考えれば循環障害につながる事が解釈されている。赤血球は機械的なせん断刺激を受け、損傷す
る結果、細胞膜要素の部分的な欠落、膜表面積の減少、細胞体積の現象、若干の球状化、密度（質量／体積）増大、変形能低下などの変化を伴う事が報告されている。これらの現象は実は細胞の加齢現象に伴っても生じる事が知られている。この類似性が両者にある事実から、過度なせん断刺激は細胞加齢を加速させるといった仮説（Kameneva MV, ASAIO J. 1995；41（3）；M457-60）も提唱されている。では、細胞が加齢・老化するという事は、酸化反応も進むのか？細胞密度毎の膜酸化量に違いが生じている事を報告した先行研究（Ando K et al. Biol Pharm Bull. 1995；18（5）；659-63）があり、加齢に伴う酸化反応が生じる事は間違いないだろう。では、せん断応力刺激に対し赤血球はその膜酸化が増大するのか？物理損傷と化学損傷ははたして同時に生じるのか？この問いに対し回答するため、我々は人工心肺使用環境を想定した血液ポンプ BP-80 駆動回路の中で血液ポンピングを実施した。その結果、３時間のせん断暴
露に対し赤血球膜タンパク量当たりの酸化量として 0.1nmol/mg の膜酸化量が増大する結果を得た（Inoueet al. Int J Artif Organs（In press））。本発表ではこれまでの関連した活動と現時点で考えられる解釈についてご報告させて頂き、老化研究分野の先生方と議論させて頂ければ幸いである。

－ 28 －

学歴
2000 年３月

芝浦工業大学工学部機械工学科卒

2002 年３月

芝浦工業大学大学院工学研究科 修士課程 機械工学専攻修了

2006 年９月

東京医科歯科大学大学院博士課程

学位取得：博士（学術）

研究歴・職歴1．2000 年４月― 2002 年３月：芝浦工業大学修士課程在籍時、東京医科歯科大学生体
材料
工学研究所生体システム分野（高谷教授）にて血液ポンプ関係の研究に従事．
2．2000 年９月― 2001 年３月：ドイツ・アーヘン工科大学ヘルムホルツ研究所 Cardiovascular Engineering 部門
研修生．
3．2005 年４月― 2006 年９月：日本学術振興会 特別研究員 DC2（東京医科歯科大学）
2006 年10月― 2007 年 3 月：日本学術振興会 特別研究員 PD（東京医科歯科大学）
4．2007 年７月― 2009 年 9 月：ドイツ・フンボルト財団奨学研究員として Charite 病院付属研究所バイオ流体
メカニクス研究室にて研究。
5．2009 年10月― 2010 年３月：芝浦工業大学ポスドク研究員
6．2010 年４月― 2013 年３月：芝浦工業大学システム理工学部生命科学科助教
7．2013 年４月― 2022 年３月：同上・准教授
8．2022 年４月１日― 現在：同上・教授・研究者情報https://orcid.org/0000-0001-9753-898X
https://www.researchgate.net/profile/Nobuo-Watanabe-2
https://researchmap.jp/read0099917
・現在の研究分野
バイオレオロジー、ヘモレオロジー、微小循環、人工臓器、心血管系の生理学、カテーテル式カーディアック・
アブレーション術支援研究、機械工学
論文実績（2022 〜）
1．M Inoue, M Ohwada, N Watanabe, The shear rate promotes pinocytosis of extracellular dextran in platelets, ClinicalHemorheology and Microcirculation, Just accepted（2024）．
2．M Inoue, Y Udono, Y Kato, K Fukui, N Watanabe, Evaluation of erythrocyte membrane oxidation due to their
exposure to shear ﬂow generated by extracorporeal blood pump, The International Journal of Artiﬁcial Organs,
Just accepted（2024）．
3．D Oshima, M Yoshida, K Saga, N Watanabe, K Wakabayashi, K Yoshimura, Mechanoresponses mediated by the
TRP11 channel in cilia of Chlamydomonas reinhardtii, iScience 26, 107926, October 20, 2023.（https://doi.org/10.1016/
j.isci.2023.107926）
4．M Higuchi, N Watanabe, Determination of the erythrocyte sedimentation rate using the hematocrit-corrected
aggregation index and mean corpuscular volume, Journal of Clinical Laboratory Analysis（Wiley）published on 1st
April 2023.（https://doi.org/10.1002/jcla.24877）
5．M Higuchi, Y Sekiba, N Watanabe, Novel blood typing method by discrimination of hemagglutination and rouleaux
using an erythrocyte aggregometer, Clinical Hemorheology and Microcirculation,（IOS Press）accepted on 11th
March 2023.
6．M Higuchi, M Tanaka, N Watanabe, Investigation of erythrocyte aggregation parameters of blood with low levels offibrinogen by syllectometry, J Biorheol 2023.
7．K Masnok, M Inoue, and N Watanabe, Direct observation of deformation of individual red blood cells in oscillatory
ﬂuid ﬂow produced using a generator of precise sinusoidal shear ﬂow. AIP Advances 12, 095020（2022）；https://doi.
org/10.1063/5.0113873,
8．Higuchi M, Watanabe N（2022）A rapid and accurate method for estimating the erythrocyte sedimentation rateusing a hematocrit-corrected optical aggregation index. PLoS ONE 17（7）：e0270977. https://doi.org/10.1371/journal.
pone.0270977
9．N Watanabe, M. Inoue, M. Honda, K. Masnok, T. Negishi, In vitro comparative study of activated clotting time in
fresh human whole blood with various levels of coagulability using two devices, J Biorheol 2022, 36（2）39-44－ 29 －

〈Special Program〉

16 June（Sun）14：40 ～ 15：00

An overview on the aging research：
the past, present, and future prospects
Speaker：Byung Pal Yu（University of Texas Health Science Center）

Chair：Yoshikazu Higami（Tokyo University of Since）

An overview on the aging research：the past, present, and future prospects
Byung Pal Yu
Department of Physiology
University of Texas Health Science Center, San Antonio, TX USA

The biological aging process is one the most intriguing and complexed problems that has
challenged not only basic biomedical scientists, but also clinical investigators who are interested
in the alleviation of age-related disease. The inherent disease involvement that compromises the
biological aging is the most urgent and practical issues underlying the aging research.
Historically, the gerontological research advancement has gone through a distinct stage：
the observation period（up to 1940s）with numerous hypotheses and theories about the causes
for the aging and the age-related diseases. The one typical theory, representing this period
is the genetically programmed life cycle：birth, growth, maturity, and senescence, leading todeath. Another proposal put forwarded during this period is the growth retardation hypothesis,
showing the slow growing, leading to the extended lifespan. Molecular exploration period.
Last decades have witnessed significant strides in aging research, fuelled by advancements inmolecular technology. Researchers have identified key epigenetic molecular changes linked toaging and age-related diseases, including the influence of epigenetic modifications on genes. This
growing body of evidence strengthens the possibility of modifying the aging process and its
associated diseases.
Molecular reductionistic exploration at gene levels during last several decades made clear thatdeeper and more precise information requires further advanced technological breakthroughs
are needed for the better understanding of aging mechanisms, like the application of quantum
technologies that will provide immeasurable vast information over molecular and gene levels
for the aging and diseases. The quantum approach with its speed, and the vast capacity ofdata process, and all other unlimited potential will revolutionize the ways aging and its’ relateddisease research by taking to another era. The application of quantum technologies, with their
exceptional speed and vast data processing capabilities, presents exciting possibilities for the
future of aging research. As an example, quantum techniques have the potential to readdress
the basic criteria of the most fundamental key data, such as biomarkers, ultimately leading
to much needed technical breakthroughs. Emerging digital and quantum technologies holdimmense potential to revolutionize the field of aging research. Quantum computing, with its
exceptional speed and vast data processing capabilities, offers exciting possibilities.
Overall, the journey of aging research has transitioned from observational theories tomolecular insights, and the future holds promise with advancements in technology, particularlyin the realm of quantum exploration.

－ 32 －

YU, BYUNG PAL, PH.D.
AFFILIATION
Department of Pathology of TX Health Science
San Antonio, TX 78299-3900,USA
E-MAIL：bpyu@usa.com
ACADEMIC EDUCATION
1956-60

Central Missouri State University, Warrensburg, MO（BS）

1960-65

University of Illinois, Urbana, IL（PhD）

PROFESSIONAL EXPERIENCE
1965-68

Instructor

Woman's Medical College of Pennsylvania

1967-71

Assistant Professor

Woman's Medical College of Pennsylvania

1971-73

Associate Professor

The Medical College of Pennsylvania

1973-78

Associate Professor

The University of Texas Health Sci. Center San Antonio, TX

1978-99

Professor

The University of Texas Health Sci. Center San Antonio, TX

1999-00

Visiting Professor

The Pusan National University, Korea

Present

Professor Emeritus

The University of Tex Health Sci. Center San Antonio, TX

HONORS AWARDED
Ho- Am Prize in Medical Science, Ho-Am Foundation, Korea
Yun-Ho Lee Award of Scientific Merit, International Aloe Scientific Council
Research and Development Award, American Diabetes Association
Selected publication
1．Chung, K.W., Kim D.H., Jung, H.J. Arulkumar, R., Chung, H.Y., Yu, B.P.：Chronic inflammation as anunderlying mechanism of ageing and ageing-related diseases. In：Biochemistry and Cell Biology of Ageing：
Part IV. Clinical Science, edited by J.R. Harris, V.I. Korolchuk, Springer, Subcellular Biochemistry 103, 2023,
pp31-44.
2．Chung, K.W., Lee, E.K., Kim, D.H., An, H.J., Kim, N.D., Im, D.S., Lee, J.W., Yu, B.P., Chung H.Y.：Age-relatedsensitivity to endotoxin-induced liver inﬂammation: Implication of inﬂammasome/1L-1 for steatohepatitis.

Aging Cell, 14（4），524-533（2015）．
3．Chung, H.Y., Lee, E.K., Choi, Y.J., Kim, J.M., Kim, D.H., Zou, Y., Kim, C.H., Lee, J, Kim, H.S., Kim, N.D., Jung,
J.H., Yu, B.P.：Molecular Inﬂammation as an Underlying Mechanism of the Aging Process and Age-relatedDiseases. J Dent Res, 90（7），830-840（2011）．
4．Yu, B.P, Masoro, E. J. and DeMartinis, F. D. Imidazole and sequestration of calcium ions by sarcoplasmic
reticulum. Nature 216：822-824, 1967.
5．Bertrand, H. A., Masoro, E. J. and Yu, B.P. Post-weaning food restriction reduces adipose cellularity. Nature
266：62-63, 1977.
6．Yu, B.P. Oxidative damage by free radicals and lipid peroxidation in aging. In：Free Radicals in Aging,edited by B. P. Yu. CRC Press, FL, 1993, pp.57-88.
7．Yu, B.P. Cellular defenses against damage from reactive oxygen species. Physiol. Rev. 74：139-162, 1994.
8．Yang, R., Yu. B.P. Critical evaluation of free radical theory of aging：A proposal of oxidative stresshypothesis. Ann. N.Y. Acad. Sci. 786：1-11, 1996.
－ 33 －

〈日本組織培養学会とのジョイントシンポジウム〉
６月 15 日（土）14：35 ～ 15：35

座長：片岡
中村

健（岡山理科大学）
庸輝（広島大学）

Innovative Gravity-Driven and Electric-Assisted Microfluidic
Culture System for Human Induced Pluripotent Stem Cell Assays
Kiyoshi Ohnuma
Department of Science of Technology Innovation,
Nagaoka University of Technology

Micro-physiological systems（MPS）offer a significant leap in cell culture technology,
employing microfabrication techniques in cell culture to emulate in vivo function. Despite thefocus on high-performance MPS featuring pump-driven flows and rapid fluidic switching tosimulate diverse biological environments, user demands gravitate towards simplicity and theability to test numerous conditions simultaneously, akin to traditional culture dishes.
To address this need, we developed a versatile MPS designed for ease of use and accessibility,
free from the complexity of high-end systems. We present a novel microfluidic culture system
based on a gravity-driven system, which does not use pumps and tubing for simplicity andscalability in MPS. The inherent challenge of gravity-driven systems, which show progressive
slowing and eventual cessation of medium flow within a day, compromises their suitability forcell culture. Our solution employs an electrically assisted ultra-slow tilting table, less than 10
degrees per day, to sustain the flow of culture medium beyond a day. We succeeded in theculture of human induced pluripotent stem cells（hiPSCs）using the system.
This system’s simplicity, eliminating the need for a complex setup, allows for an expanded
array of test conditions on a single platform. The ease of integration with existing culture
methodologies, coupled with low implementation costs, positions our MPS as a pivotal
technology for culture experiments in a laboratory and screening the safety and efficacy ofpharmaceuticals, cosmetics, and health supplements. Our development marks a stride towards
user-friendly, general-purpose MPS, promising to stabilize culture conditions and enhance
reproducibility
Reference
Limjanthong, N. et al. Gravity-driven microfluidic device placed on a slow-tilting table enables constantunidirectional perfusion culture of human induced pluripotent stem cells. Journal of Bioscience andBioengineering 135, 151-159（2023）．
氏

名：大沼清（おおぬまきよし）機

関：国立大学法人

部

署：技学研究院

職

名：准教授

学

位：博士（理学）平成 11（1999）年２月 26 日（名古屋大学）

長岡技術科学大学
技術科学イノベーション系／物質生物工学系（兼任）

テーマ：イセエビの神経筋接合部シナプス前末端における協同的なカルシウム除去機構
1998 年３月

名古屋大学大学院理学研究科 博士後期課程物理学専攻 単位取得退学

1998 年６月

カリフォルニア大学バークレー校 分子細胞生物 博士研究員

2000 年５月

東京大学大学院総合文化研究科

2010 年４月

長岡技術科学大学 特任准教授

2014 年４月

現職 准教授教務補佐員、研究員、助手、特任助教、特任講師－ 36 －

Development of cell self-aggregation technique-based tissue
engineering. -Challenges for applications in regenerative medicine
and 3D culture modelsRyosuke Iwai
Institute of Frontier Science and Technology, Okayama University of Science

We have developed the cell self-aggregation induction technique（ CAT）．Cells seeded
confluently on the surface of a culture dish coated with polymer solution developed for CAT
adhere to form a single-layer cell sheet with no gaps, then spontaneously detach from thepolymer-coated surface and simultaneously aggregate to form a single cell aggregate within
one day after seeding1-3. By designing the shape and number of CAT polymer coatings, threedimensional cell aggregates that follow the two-dimensional polymer coated region could form
spontaneously on the culture dish, like a pop-up picture. Then, we have succeeded in ultraefficiently preparing uniform spherical cell aggregates of desired size at a production density
300 times higher than that of conventional commercial culture dishes by dot-printing a polymer
solution at high density using an ink-jet device4. We have also succeeded in preparing 3D cellaggregated tissues that reproduce the specific shapes of living organs, such as ring, fiber andband by controlling the aggregation of cell monolayer sheets using specially-designed silicone
culture molds5-8.
In this presentation, we would like to introduce the concept of the CAT-based 3D cellaggregated tissue fabrication and its application potential to regenerative medicine and drug
discovery testing, and discuss the possibility of further application for the fabrication of organlike tissue with shape, structure, and function that could completely replace a living organ.
関連代表論文1．Biomaterials . 2013；34（36）：9096-102.
2．J Biomed Mater Res A . 2016；104（1）：305-12.
3．J Biomed Mater Res B Appl Biomater . 2017；105（5）：1009-1015.
4．特願 2020-028119，細胞凝集塊の製造方法
5．Nature Biomedical Engineering . 2021；5（8）：926-940.
6．Biomed Mater . 2022；17（6）：065021
7．Sci Rep . 2022；12（1）：202798．Biomed Mater . 2022；17（6）：065021
略歴：2010 年 3 月

北海道大学科学技術コミュニケーター教育研究部門（CoSTEP）修了

2011 年 3 月

北海道大学大学院工学研究科 生物機能高分子専攻
博士後期課程修了

2011 年 4 月

博士（工学）

独立行政法人 国立循環器病研究センター研究所 生体医工学部
流動研究員

2014 年 4 月

国立研究開発法人 国立循環器病研究センター研究所 生体医工学部
特任研究員

2016 年 4 月

岡山理科大学 研究推進機構

技術科学研究所

講師（PI）
2024 年 4 月

岡山理科大学 研究・社会連携機構

フロンティア理工学研究所

准教授（PI）
現在に至る－ 37 －

Acute brain slice preparations for approaching cellular andmolecular mechanisms of higher brain function
Sho Kakizawa
Tokyo Metropolitan Institute for Geriatrics and Gerontology

我々の脳の高次機能のメカニズムを細胞・分子レベルで理解することは、認知症を始めとする脳機能の異常を伴う疾患のメカニズムの理解、ひいてはそれに基づく治療法の開発へと繋がる。神経科学の分野では様々な実験標本が用いられているが、初代培養細胞とともに最も多く使用されている実験標本の一つが、脳スライス標本である。その中でも、脳を生体内から摘出したのち、生きた状態のまま維持するものを「急性脳スライス標本（acute brain slice preparation）」と呼ぶ。この急性スライス標本の作製は、大脳皮質、海馬、小脳など、多くの脳領域に適応可能である。そして、標本作成後、一定の時間内では、生体内での細胞構築や神経細胞同士の接続（シナプス結合）を保った状態で解析が可能であるという大きな利点を有する。このため、急性脳スライス標本は、細胞・分子レベルを中心として、神経科学の発展に大きく寄与してきた。
急性脳スライス標本は、生体から摘出されているため、心拍や呼吸、個体レベルでのストレス等の影
響を受けないことから、様々な解析手法と組み合わせることが可能である。例えば、ホールセルパッチ
クランプ法などの電気生理学的手法と組み合わせることで、記憶学習の細胞レベルでの基盤となるシナ
プス可塑性の解析が可能となる。あるいは、カルシウムイメージング法などのイメージング法と組み合わせることで、神経活動に依存したシグナル動態の変化が明らかにされる。本講演では、演者が急性小脳スライス標本を用いて行ってきた研究を具体例として、急性脳スライス標本の利点や基礎老化研究における可能性について紹介したい。
〈関連文献〉
Kakizawa S, Arasaki T, Yoshida A, Sato A, Takino Y, Ishigami A, Akaike T, Yanai S, Endo S.（2024）．Essential role of
ROS -8-Nitro-cGMP signaling in long-term memory of motor learning and cerebellar synaptic plasticity. Redox Biol 70,
103053.
Kakizawa S, Kishimoto Y, Yamamoto S, Onga K, Yasuda K, Miyamoto Y, Watanabe M, Sakai R, Mori N.（2020）．
Functional maintenance of calcium store by ShcB adaptor protein in cerebellar Purkinje cells. Sci Rep. 10, 14475.
Kakizawa S, Shibazaki M, Mori N.（2012）．Protein oxidation inhibits NO-mediated signaling pathway for synaptic
plasticity. Neurobiol Aging 33, 535-45.
Namiki S, Kakizawa S, Hirose K, Iino M.（2005）．NO signalling decodes frequency of neuronal activity and generates
synapse-specific plasticity in mouse cerebellum. J Physiol 566, 849-63.
Okubo Y, Kakizawa S, Hirose K, Iino M.（2001）．Visualization of IP3 dynamics reveals a novel AMPA receptor-triggered
IP3 production pathway mediated by voltage-dependent Ca2+ inﬂux in Purkinje cells. Neuron 32, 113-22.

〈略歴〉
1991

東京大学理学部卒業

1993

東京大学理学系研究科修士課程修了

1996

東京大学理学系研究科博士課程終了、博士（理学）取得

1996- 理化学研究所国際フロンティア研究システム / 脳科学総合研究センター、研究員
1998- 科学技術振興機構 CREST 研究員
2000- 東京大学医学系研究科 助手 / 助教
2008- 長崎大学医歯薬学総合研究科 講師
2010- 京都大学薬学研究科 准教授
2024- 東京都健康長寿医療センター研究所－ 38 －

Microglial xCT is a novel therapeutic target for Alzheimer’sdisease◦Yugo Kato1, Hidetoshi Nagamine1, Masahiro Kanatani1, Yosuke Horikoshi1,
Kazuhiro Nakaso1
1．Division of Biochemistry, Faculty of Medicine, Tottori University

The role of activated microglia has been reported in Alzheimer’s disease（AD），and aging
brain has given a great interest in recent years. The toxicity of extracellular glutamate forneurons is well known as one of the mechanisms of neuronal death in neurodegenerative
disorders such as AD. However, the molecular mechanism how extracellular glutamate increasein the brain with AD has not been well understood.
System x（xc-），a cystine/glutamate antiporter, takes cystine into cells and releasescglutamate to the extracellular space. xCT, a component of xc-, is induced under several
pathogenic conditions and enhances the function of xc-. Our previous study indicates that theexpression of xCT is induced in microglia and xc- is a source of the extracellular glutamate.
Based on these backgrounds, we investigated the role of xCT on AD pathology. Firstly, we
found the expression of xCT in microglia in AD mice brain. Furthermore, exposure of amyloid
beta to the microglia cell line 6-3 cells upregulated xCT expression and glutamate concentrationin the conditioned medium. Next, we measured the behavioral changes in xCT deficient AD
model mice using Y-maze and Morris water maze test. While the cognitive function of AD micedecreased compared to that of wildtype mice, the decrease of cognitive function was prevented
in xCT deficient AD mice. Additionally, treatment with xCT inhibitor inhibited the decrease ofcognitive function in AD mice. These results indicated that the glutamate from xc- involved in
AD pathology, and microglial xCT may be a novel therapeutic target for AD.
Keywords：Alzheimer’s disease, System xc-, xCT,

氏名：加藤

優吾

所属：鳥取大学医学部医学科病態解析医学講座生化学分野
学歴
1．芝浦工業大学・システム理工学部・生命科学科

2017 年３月卒業

2．同大学大学院・理工学研究科・システム理工学専攻

学士（生命科学）2019 年３月修了

修士（システム理工学）
3．同大学大学院・理工学研究科・機能制御システム専攻

2022 年３月修了

博士（工学）
職歴
1．2022 年４月 - 2023 年３月

芝浦工業大学、博士研究員

2．2022 年４月 - 2024 年３月

東京都健康長寿医療センター研究所

3．2023 年４月 - 現在

鳥取大学、助教

協力研究員

研究ビタミン E などの天然に存在する物質の老化に対する影響を研究してきました。現在は、神経・精神疾患と肥満の分子病態（特に xCT との関連）に興味があり、研究を行っています。
－ 39 －

〈 Japan-Korea Joint Symposium〉
15 June（Sat）16：30 ～ 18：10

Chairs：Sho Kakizawa（Tokyo Metropolitan Institute for
Geriatrics and Gerontology）
Cheol-Koo Lee（Korea University）

Genomic approach to identify the role of DNA repair in longevity using
genomic databases
Young Rok Seo
Department of Life Science, Institute of Environmental Medicine, Dongguk University

As the global aging population increases, it becomes crucial to identify factors contributing
to longevity and aging. Many studies have highlighted the importance of maintaining genomic
stability in centenarian populations, but the exact reasons for longevity remain unclear becauseof the complexity of various factors involved. In this study, we assessed human longevity
and healthy aging, focusing on the role of DNA repair in maintaining genome integrity. We
suggested novel approaches for assessing longevity-associated genetic profiles related to
DNA repair using genomic databases. Among the biomarkers obtained from the longevity
database, we identified DNA repair-related genes, analyzed potential gene groups, and yielded
16 integrally significant biomarkers. We also conducted text mining-based pathway analysis tointerpret the biological network of each gene and the role of DNA repair in longevity. Network
analysis revealed TP53, ATM, and SIRT1 as key factors, suggesting that their genetic profiles
can be considered key nodes to explain the genetic contribution of key DNA repair factors
to longevity and healthy aging. We aim to adapt further approaches to assess the prediction
accuracy of the aforementioned potential key genes using actual experiment-based big data.
In summary, this study underscores the significance of DNA repair activity in longevity andaging. Our approach can be used to identify potential key factors, understand the role of DNA
repair, and use genomic databases to elucidate the contribution of genetic factors to longevity invarious areas.

－ 42 －

Young Rok Seo, Ph.D.

Young Rok Seo, Ph.D.

Academic appointments：

Director,
Institute of Environmental Medicine, Dongguk University, Seoul, Korea
Academic
appointments:

2010-Present）Medicine, Dongguk University, Seoul, Korea (November,
Director,（November,
Institute of Environmental
Professor, Department of Life Science, Dongguk University, Seoul, Korea（March,
2010-Present)

Professor,2012-February,
Department ofpresent）
Life Science, Dongguk University, Seoul, Korea (March, 2012February,Associatepresent) Professor, Department of Life Science, Dongguk University, Seoul, Korea （September,2012） of Life Science, Dongguk University, Seoul, Korea (September, 2010-February, 2012)
Associate2010-February,
Professor, Department& Professor,
Associate Department
Professor, Departmentof Pharmacology,
School ofKyung
Medicine,
Hee Seoul,
University,
AssistanceAssistance& Associateof Pharmacology,
School of Medicine,Hee Kyung
University,
Korea
Seoul, Korea（March,(March, 2003-August,2010) 2003-August, 2010）
Education& Training：
Education& Training:
Indiana University
CancerINCenter,
IN（Nov 1999
～ Feb
2003）Research& Postdoctoral
Indiana University
Cancer Center,(Nov 1999～Feb
2003)
Research
AssociateAssociate& Postdoctoral
Fellow Fellow
Korea University,
Seoul,
Korea（Sep 19961999)～ Aug1999）Ph.D.
in Molecular
Korea University,
Seoul, Korea(Sep
1996～AugPh.D.
in Molecular
BiologyBiology
Korea University,
Seoul,
Korea（Sep 19941996)～ Aug
1996）M.S.
in Applied
Entomology
Korea University,
Seoul, Korea(Sep
1994～AugM.S.
in Applied
Entomology
Korea University,
Seoul,
Korea（Sep 19941996)～ Aug
1996）B.S.
in Agricultural
Korea University,
Seoul, Korea(Sep
1994～AugB.S.
in Agricultural
Biology Biology
Publications：
Selected Selected
Publications:

Jang,
& &
Na,Shin,
HW.DY.
& Shin,DY.
& Han,
Lee, J.
Han, HS.
JP., &Kim,
HS.
& Choi,Kim, EJ.,
SJ., Choi,
EJ.,Hong,
Lee, C.,Hong,
1. Jang,1．
Y. &
Na,Y.
HW.
& Lee,
J. &JP.,&Kim,
Kim,
SJ.,
Lee, C.,
YD.,
Kim,YD.,
HJ.,
HJ., Integrative
Seo, YR.（2024）．Integrative
analysis of RNA-sequencing
andfor theidentification
Seo, YR.Kim,(2024).
analysisof RNA-sequencing
and microarray forthemicroarray
identificationof adverse
effectsofof
adverseoneffhumanects ofskin.
UVBFrontiers
exposurein on
humanskin.12,
Frontiersin (Corresponding
Public Health, 12,1328089.（Corresponding
UVB exposure
PublicHealth,1328089.
Author)Author）
2. Kim, HS.,Na, HW., Jang, Y., Kim, SJ., Kee, NG., Shin, DY., Choi, HJ., Kim, HJ., Seo, YR. (2022). Integrative analysis
2．Kim,Na, HW.,
Jang, Y., between
Kim, SJ., environmental
Kee, NG., Shin, skin
DY.,diseases
Choi, HJ.,Kim,
HJ., Seo,
YR.（2022）．Integrative
to explore
theHS.,
biologicalassociation
andambient
particulatematter.
Scientificanalysis
explore the biologicalreports, 12,9750.to(Corresponding
Author)association between environmental skin diseases and ambient particulatematter.
c reports,
12, 9750.
Author）
3. Kang, DS.,
Lee, Scientifi
NH., Shin,
DY., Jang,Y., （Corresponding
Lee, SH., Lim, KM.,
Ahn, YS., Lee, CM., Seo, YR. (2022). Network-based
3．Kang,DS., Lee,
Shin,effects
DY., Jang,
Y., Lee, SH., Lim, KM.,
Ahn, YS., Lee,
CM., Seo, exposure
YR.（2022）．Networkintegrated
analysisforNH.,
toxic
of high-concentration
formaldehyde
inhalation
throughthebased integrated
analysis for
toxic effof high-concentration
formaldehyde inhalation exposure throughtoxicogenomic
approach. Scientificreports,
12,ects
5645.
(Corresponding Author)
toxicogenomicc reports,
12, 5645.
4. Kim, SJ.,the
Kim,
NH., Park, approach.
SH., Kim,Scientifi
HS., Song,
JJ., Son,
BS.,（Corresponding
Jang, AS., Park,Author）
MK., & Seo, YR. (2020). Genomic

4．Kim,
SJ., Kim,
NH., Park,
SH., Kim,
HS., Song,
JJ., Son,
Jang, AS.,
Park,exhaustMK., & particles
Seo, YR.（2020）
approach
to explore
alteredsignaling
networksof olfaction
inBS.,
response
to dieselin mice.．Genomic
Scientificapproach
explore alteredAuthor)
signaling networks of olfaction in response to diesel exhaust particles in mice.
reports, 10,16972.to(Corresponding

Scientifi
c reports,
10, 16972.
（Corresponding
Author）
5. Kim, HS.,Kim, YJ.,
Kim, SJ.,
Kang,
DS., Lee, TR., Shin,
DW., Kim, HJ., & Seo, YR. (2019). Transcriptomic analysis

5．Kim,
HS., fibroblast
Kim, YJ., Kim,
SJ., Kang,DS., Lee,
TR., Shin, underlying
DW., Kim, HJ.,
& Seo, YR.
（2019）．Transcriptomicof humandermalcells reveals
potential
mechanisms
the protective
effectsofvisible red lightanalysisfromof humandermalfibroblast
cellsofreveals
potential Science,mechanisms
underlying
protective effAuthor)ects ofagainst damage
ultraviolet
B light.
JournalDermatological
94 (2),
276-283.the(Corresponding
visible red light against damage from ultraviolet B light. Journal of Dermatological Science, 94（2），276-283.
（Corresponding Author）

57－ 43 －

Adverse Effects of Environmental Pollutants on Neural Stem Cells and Adult
Hippocampal Neurogenesis
Jaewon Lee
Department of Pharmacy, College of Pharmacy, Pusan National University

It is widely acknowledged that the brain possesses lifelong adaptability and the capacity toform new neural pathways, a phenomenon known as adult neurogenesis, which holds significant
implications for our understanding of neuroplasticity. Adult neurogenesis is influenced by amulti-factors such as aging, physical activity, metabolism, social engagement, stress, and sleep,
all of which play a role in shaping learning and memory processes. Despite these findings, thecomplete functional implications and clinical applications of adult neurogenesis remain under
exploration. This capability offers promise for improving treatments and rehabilitation forneurological disorders by harnessing factors that promote adult neurogenesis to facilitate brain
recovery post-injury. Yet, further research is imperative given the nascent stage of this field.
We have demonstrated the enhancement of adult neurogenesis through dietary restriction,
which can mitigate the aging process, and has also identified the detrimental effects ofenvironmental toxins. In this study, we aim to investigate the impact of various environmental
stressors on neural stem cells and adult neurogenesis, thereby elucidating their influence on thebrain’s learning and memory functions.
Keywords：Dietary restriction, Environmental toxicants, Neurogenesis－ 44 －

Jaewon Lee, Ph.D., Professor
Department of Pharmacy, College of Pharmacy
Pusan National University, Busan 46241, Republic of Korea
Academic appointments：
2004-Present

Assistant Professor / Associate Professor / Professor
College of Pharmacy, Pusan National University, Busan, Korea

2020-Present

Director, Division of BITID, College of Pharmacy,
Pusan National University, Busan, Korea

2020-2022

Dean, College of Pharmacy,
Pusan National University, Busan, Korea

2019-Present

Vice Dean, PNU International,
Pusan National University, Busan, Korea

2013-2014

Visiting Professor, Laboratory of Neurosciences,
National Institute on Aging, Baltimore, MD, USA

Education & Training：
2002

Ph.D., University of Kentucky, Lexington, KY, USA

1997

M.S., Yonsei University, Seoul, Korea

1993

B.S., Yonsei University, Seoul, Korea

Selected Publications：
1．Low-dose curcumin enhances hippocampal neurogenesis and memory retention in young mice. Arch Pharm
Res. 2023 May；46（5）：423-437
2．Dispersant-free supra single-walled carbon nanotubes for simultaneous and highly sensitive biomoleculesensing in ex vivo mouse tissues. Carbon. 2023 Sep；213：118275
3．Cationic nanoplastic causes mitochondrial dysfunction in neural progenitor cells and impairs hippocampal
neurogenesis. Free Radic Biol Med. 2023 Nov 1；208：194-210.
4．Conductive PEDOT：PSS copolymer electrode coatings for selective detection of dopamine in ex vivo
mouse brain slices. Talanta. 2024 Jan 15；267：125252.
5．Glutamate oxidase sheets-Prussian blue grafted amperometric biosensor for the real time monitoring ofglutamate release from primary cortical neurons. Int J Biol Macromol. 2023 Nov 6；254（Pt 2）：127903.

－ 45 －

Suppression of neutrophil mitigates acute aortic dissection in H2-inhalation
therapy◦Masumi Iketani1, Toshiyuki Aokage1, 2, Mitsuhiro Kawata1, 3, Yasunori Fujita1,
Masafumi Ito1, Ikuroh Ohsawa1
1．Biological Process Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology
2．Department Emergency Critical Care and Disaster Medicine, Okayama University Graduate School
Medicine Dentistry and Pharmaceutical Sciences
3．Cardiovascular Surgery, Tokyo Metropolitan Institute for Geriatrics and Gerontology

Acute aortic dissection is a geriatric disease caused by hypertension and atherosclerosis.
Hypertension causes damage to the vascular endothelium of the aorta, leading to blood
infiltration into the tunica media, and resulting in dissections between intima and adventitia.
During this process, the migration of neutrophils promotes vascular inflammation, increasing
the risk of aortic dissection followed by aortic rupture and other fatal complications. Matrix
metalloproteinases（MMPs）and inflammatory cytokines secreted by neutrophils are known
to cause aortic dissection and rupture. Molecular hydrogen（H 2），an antioxidative and antiinflammatory agent, has been reported to inhibit inflammatory cytokines and MMPs, suggesting
beneficial effects on various geriatric diseases. However, it is unclear whether inhalation of H2
gas inhibits or alleviates the progression of acute aortic dissection. In this study, we examinedthe effects of H2 using a mouse model of acute aortic dissection. Inhalation of 2% H2 gas for 24hours immediately after induction of acute aortic dissection improved survival and decreased
the incidence of aortic rupture. Regions of aortic dissection were reduced in the H2 gasinhalation group. In addition, MMP-9 and IL-6 elevations in plasma caused by aortic dissection
were inhibited in the H2 gas-inhalation group. Furthermore, the migration of neutrophils into
the aortic wall was inhibited in the H2 gas-inhalation group. These results suggest that H2 may
inhibit aortic dissection and aortic rupture through inhibition of neutrophil activation.
Keywords：Aorta, Inflammation, MMP-9－ 46 －

Masumi Iketani Ph.D.
Tokyo Metropolitan Institute for Geriatrics and Gerontology
Biological Process of Aging
E-mail：iketani@tmig.or.jp-----------------------------------------------------------------------------------------EDUCATION
2012 March
Ph.D. in Medicine, Yokohama City University Graduate School of Medicine
2006 March
B.S. in Science, Kitasato University
PROFESSIONAL EXPERIENCE
2014 - present
Researcher, Tokyo Metropolitan Institute of Gerontology, Biological Process of Aging
2012 April - 2014 March
Post-doctoral fellow, Yokohama City University Graduate School of Medical Life Science, Molecular Medical
Bioscience Laboratory
SELECTED RECENT PUBLICATIONS
1．Aokage T, Iketani M, Seya M, Meng Y, Ageta K, Naito H, Nakao A, Ohsawa I. Attenuation of pulmonary
damage in aged lipopolysaccharide-induced inflammation mice through continuous 2% hydrogen gas
inhalation：A potential therapeutic strategy for geriatric inflammation and survival. Experimental

Gerontology , 180：112270, 2023.
2．Iketani M, Sakane I, Fujita Y, Ito M, Ohsawa I. H2-induced transient upregulation of phospholipids with
suppression of energy metabolism. Medical Gas Research , 13, 3, 133-141, 2023.
3．Aokage T, Seya M, Hirayama T, Nojima T, Iketani M, Ishikawa M, Terasaki Y, Taniguchi A, Miyahara N,
Nakao A, Ohsawa I, Naito H. The effects of inhaling hydrogen gas on macrophage polarization, fibrosis, andlung function in mice with bleomycin-induced lung injury. BMC Pulmonary Medicine , 21：339, 2021.
4．Terasaki Y, Suzuki T, Tonaki K, Terasaki M, Kuwahara N, Ohsiro J, Iketani M, Takahashi M, Hamanoue
M, Kajimoto Y, Hattori S, Kawaguchi H, Shimizu A, Ohsawa I. Molecular hydrogen attenuates gefitinibinduced exacerbation of naphthalene-evoked acute lung injury through a reduction in oxidative stress andinﬂammation. Laboratory Investigation , 99, 793-806, Feb, 2019.
5．Iketani M, Sekimoto K, Igarashi T, Takahashi M, Komatsu M, Sakane I, Takahashi H, Kawaguchi H, OhtaniKaneko R, Ohsawa I. Administration of hydrogen-rich water prevents vascular aging of the aorta in LDL
receptor-deficient mice. Scientific Reports , 8：16822, 14 Nov, 2018.
6．Iketani M, Ohshiro J, Urushibara T, Takahashi M, Arai T, Kawaguchi H, Ohsawa I. Preadministration ofhydrogen-rich water protects against lipopolysaccharide-induced sepsis and attenuates liver injury. Shock ,48（1），85-93, 2017.
7．Igarashi T, Ohsawa I, Kobayashi M, Igarashi T, Suzuki H, Iketani M, Takahashi H. Hydrogen prevents
corneal endothelial damage 1 in phacoemulsification cataract surgery. Scientific Reports , 6：31190, 8 Aug,2016.

－ 47 －

Lifespan extender rapamycin and TOR genetics in budding yeast cells
Cheol-Koo Lee
Korea University, Seoul, Republic of Korea

Target of rapamycin（TOR）has been well-studied for rapamycin in the aging research. The
highly conserved protein TOR is known to regulate signaling pathways through its multiprotein
complexes TORC1 and TORC2. The relationship between TOR and its inhibitor, rapamycin,
in lifespan extension has been extensively studied. FK506-sensitive proline rotamase 1 protein（Fpr1p），which is a homologue of the mammalian prolyl isomerase FK506-binding proteinof 12 kDa（FKBP12），is known to play important roles in protein folding and prevention ofprotein aggregation. Although rapamycin is known to bind to Fpr1p to inhibit Tor1p mediatedmechanistic Target Of Rapamycin（mTOR）activity, the physiological functions of Fpr1p onlifespan remain unclear. The importance of FPR1 for rapamycin-induced lifespan extension will
be discussed. While mammals possess a single TOR gene, the budding yeast Saccharomyces
cerevisiae harbors two TOR paralogs：TOR1 and TOR2. The different genetics of TOR1
and TOR2 will be discussed as well. Our results hold a strong insight for the mechanism of
rapamycin to TOR.
Keywords：Rapamycin, TOR, Lifespan－ 48 －Name：Cheol-Koo Lee
Academic appointments：
Professor, Associate Professor, Assistant Professor, Korea University, Seoul, Republicof Korea（2005-Present）
Education & Training：
University of North Carolina-Chapel Hill, USA（2003-2004）
Postdoctoral fellow
University of Wisconsin-Madison, USA（1998-2003）
Ph.D. in Molecular & Environmental Toxicology Center
Selected Publications：
1．Yalcin G, Kim J, Seo D, Lee CK # . FPR1 is essential for rapamycin-induced lifespan extension in
Saccharomyces cerevisiae. Biochem Biophys Res Commun. 2023 Apr 23；653：76-82（ #corresponding
author）．
2．Kwon YY, Kim SS, Lee HJ, Sheen SH, Kim KH, Lee CK#. Long-living budding yeast cell subpopulationinduced by ethanol/acetate and respiration. J Gerontol A Biol Sci Med Sci. 2020 Jul 13；75（8）：1448-1456（#corresponding author）．

－ 49 －

Effects of resistance training on fibro-adipogenic progenitors in aging skeletal
muscle◦Yung-Li Hung1,2, Ayami Sato3, Yuka Takino3, Akihito Ishigami3 & Shuichi Machida2
1．Japan Society for the Promotion of Sciences, Tokyo, Japan
2．Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan
3．Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, JapanThe accumulation of senescent cells in numerous tissues contributes to multiple aging-related
pathologies. Fibro-adipogenic progenitors（FAPs）play a critical role in homeostasis of skeletal
muscle such as muscle regeneration and maintenance of skeletal muscle mass. Senescent FAPs
impair muscle satellite（stem）cell differentiation and contribute to skeletal muscle atrophy andfibrosis. On the other hand, exercise training is thought to exert anti-aging effects. Resistancetraining improves skeletal muscle mass during aging. However, the effects of resistance training
on FAPs in aging skeletal muscle is unclear. Twenty-two-month-old female rats were divided
into sedentary and training groups. The rats in the training groups were trained to climb
a ladder while bearing a load for a total of 20 training sessions over two months. After twomonths, the flexor hallucis longus muscles were collected and analyzed. Senescent cells wereidentified by using a senescence-associated β- galactosidase stain and p21 IHC stain, and FAPs
were identified by using PDGFR-α IHC stain. The results indicate that the all and type IIx/
IIb muscle fiber cross-section area was significantly reduced in the 24-month-old sedentarygroup compared with that in the 18-month-old sedentary group；however, the cross-section
area increased after climbing training（p < 0.05）．In particular, the number of senescent cells
was profoundly reduced in the 24-month-old training group（p < 0.05）．Most of the senescentcells were FAPs. The number of senescent FAPs was greatly increased in the 24-month-old
sedentary group compared with the 18-month-old sedentary group（p < 0.05）．Furthermore,
the number of senescent FAPs was significantly reduced in the 24-month-old climbing training
group（p < 0.05）．These results suggest that resistance training has a senolytic effect on aging
female rat skeletal muscle.
Keywords：Sarcopenia, Resistance training, Senolytic effect－ 50 －

Present position
Japan society for the promotion of science（JSPS）International Fellowships for Research inJapan

Education
Graduate School of Sport Sciences, Waseda University, Japan（Ph.D.）（ Sport Sciences）（2012/04-2018/01）
Department of Physiology & Master’s Program, Kaohsiung Medical University, Taiwan（M.Sc.）（Sciences）（2007/09-2009/06）
Department of Sports Medicine, Kaohsiung Medical University, Taiwan（B.A.）（Sciences）（2003.09-2007.06）

Previous Appointments
Postdoctoral Fellow, Japan society for the promotion of science（JSPS）International Fellowships for Research in Japan（2023.04-now）
Postdoctoral Fellow, Institute of Health and Sports & Medicine, Juntendo University, Japan（2018.04-2023.03）

Honors and awards
The Descente and Ishimoto Memorial Foundation for the Promotion of Sports Science（2019）
Society for Women's Health Science Research（2019）

Publication
1． Ishido M, Hung YL, Machida S, Aquaporin 4 Expression Level Is Decreased in Skeletal Muscles with Aging, Kobe
J Med Sci, 69（2）：E40-E48, 2023.
2． Kurosaka M, Hung YL, Shuichi Machida S, Kohda K, IL-4 Signaling Promotes Myoblast Differentiation and Fusion
by Enhancing the Expression of MyoD, Myogenin, and Myomerger, Cells, 12（9）：1284, 2023.
3． Hung YL, Sato A, Takino Y, Ishigami A, Machida S, Inﬂuence of oestrogen on satellite cells and myonuclear domain
size in skeletal muscles following resistance exercise, J Cachexia Sarcopenia Muscle, 13（5）：2525-2536, 2022.
4． Hung YL, Kosugi R, Natsume T, Machida S, Loquat leaf extract enhances muscle contraction-induced activation ofprotein synthesis signaling in rat skeletal muscle, Evid Based Complement Alternat Med, 2022：2234118, 2022.
5． Nozaki R*, Hung YL＊, Takagi K, Nakano D, Fujii T, Kawanishi N, Okamoto T, Machida S, Differential protective
effects of Radix astragali, herbal medicine, on immobilization-induced atrophy of slow-twitch and fast-twitch muscles,
Biomed Res, 41（3）：139-148, 2020.＊：These authors contributed equally to this work.
6． Hung YL, Wang SC, Suzuki K, Fang SH, Chen CS, Cheng WC, Su CC, Yeh HC, Tu HP, Liu PL, Huang MY, Li CY,
Bavachin attenuates LPS-induced inﬂammatory response and inhibits the activation of NLRP3 inﬂammasome inmacrophages, Phytomedicine, 59：152785, 2019.
7． Yang CY, Hung YL, Tang KW, Wang SC, Tseng CH, Tzeng CC, Liu PL, Li CY, Chen YL, Discovery of
2-Substituted 3-Arylquinoline Derivatives as Potential Anti-Inflammatory Agents Through Inhibition of LPSInduced Inﬂammatory Responses in Macrophages, Molecules, 24（6）：1162, 2019.
8． Huang MY, Tu CE, Wang SC, Hung YL, Su CC, Fang SH, Chen CS, Liu PL, Cheng WC, Huang YW, Li CY, Corylin
inhibits LPS-induced inﬂammatory response and attenuates the activation of NLRP3 inﬂammasome in microglia,
BMC Complement Altern Med, 18（1）：221, 2018.
9． Lin KH, Huang MY, Cheng WC, Wang SC, Fang SH, Tu HP, Su CC, Hung YL, Liu PL, Chen CS, Wang YT, Li CY,
RNA-seq transcriptome analysis of breast cancer cell lines under shikonin treatment, Sci Rep, 8（1）：2672, 2018.
10．Li CY, Suzuki K, Hung YL, Yang MS, Yu CP, Lin SP, Hou YC, Fang SH, Aloe metabolites prevent LPS-induced
sepsis and inﬂammatory response by inhibiting mitogen-activated protein kinase activation, Am J Chin Med, 45（4）：847-861, 2017.
11．Hung YL, Fang SH, Wang SC, Cheng WC, Liu PL, Su CC, Chen CS, Huang MY, Hua KF, Shen KH, Wang YT, Suzuki K,
Li CY, Corylin protects LPS-induced sepsis and attenuates LPS-induced inﬂammatory response, Sci Rep, 7：46299,
2017.
12．Wu SC, Hsiao HF, Ho ML, Hung YL, Chang JK, Wang GJ, Wang CZ, Suppression of discoidin domain receptor 1
expression enhances the chondrogenesis of adipose-derived stem cells, Am J Physiol Cell Physiol, 308（9）：C685-696,
2015.

－ 51 －

The aging process is an evolutionary phenomenon from the tumor’sperspective
Tae Jun Park
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine

He term “evolution” used in this study specifically denotes the phenotypic transition towards
a higher metastatic potency from well-formed glandular structures to collective invasion,
ultimately resulting in the development of cancer cell buddings at the invasive front. Ourfindings highlight the spatial correlation of this evolution with cancer cell senescence, revealing
distinct types of senescent tumor cells（Type I and Type II）that play different roles in theoverall cancer progression. Type I senescent tumor cells（p16INK4A+/CXCL12+/LAMC2-/MMP7-）
are identified in the collective invasion region, while Type II senescent tumor cells（p16INK4A+/CXCL12+/LAMC2+/MMP7+），representing the final evolved form, are prominently located in
the partial-EMT region. Importantly, Type II senescent tumor cells strong association with local
invasion and lymph node metastasis in colorectal cancer, potentially impacting patient prognosis.

－ 52 －

Tae Jun Park MD, PhD
Academic appointments：
Ajou University School of Medicine, Suwon, South Korea
Assistant, Associate and Full Professor, School of Medicine（Mar 2015～
Present）
Education & Training：
UCSD, USA（2012～2013）
Visiting Scholar, Department of Medicine, with Prof. Brenner
Hiroshima University, Japan（2004～2006）
Postdoctoral Fellow in Biological Science
Ajou University, School of Medicine, Suwon, South Korea（1997～2001）
Ph.D. in Biochemistry and Molecular Biology, with Prof. In Kyoung Lim
Ajou University, School of Medicine, Suwon, South Korea（1989～1995）
M.D. in Medicine
Selected Publications：
1．Park SS, Lee YK, Choi YW, Lim SB, Park SH, Kim HK, Shin JS, Kim YH, Kim JH# and Park TJ#（2024）
Cellular Senescence is Associated with the Spatial Evolution Towards a Higher Metastatic Phenotype inColorectal Cancer. Cell Reports （, #corresponding author）
2．Kim YH, Lee YK, Park SS, Park SH, Eom SY, Lee YS, Lee WJ, Jang J, Seo D, Kang HY, Kim JC, Lim
SB, Yoon G, Kim HS, Kim JH#, and Park TJ#（2023）Mid-Old Cells are A Potential Target for Anti-aging
Interventions in the Elderly. Nature Communications（#corresponding.
author）
3．Park YJ, Kim JC, Kim Y, Kim YH, Park SS, Muther C, Tessier A, Lee G, Gendronneau G, Forestier S,
Ben-Khalifa Y, Park TJ#, and Kang HY#（2023）Senescent melanocytes driven by glycolytic changes arecharacterized by melanosome transport dysfunction. Theranostics （. #corresponding author）
4．Park SS, Choi YW, Kim JH, Kim HS# and Park TJ #（2021）Senescent Tumor Cells：An Overlooked
Adversary in the Battle Against Cancer. Exp. Mol. Med（#corresponding author）
5．Choi YW, Kim YH, Oh SY, Suh KW, Kim YS, Lee GY, Yoon JE, Park SS, Lee YK, Park YJ, Kim HS, Park
SH, Kim JH# and Park TJ#（2021）Senescent Tumor Cells Build a Cytokine Shield in Colorectal Cancer.

Advanced Science （. #corresponding author）
6．Kim YH, Choi YW, Lee J, Soh EY, Kim JH# and Park TJ#（2017）Senescent tumor cells lead the collective
invasion in thyroid cancer. Nature Communications（, #corresponding author）－ 53 －

Changes of nucleocytoplasmic trafficking in cellular senescence
Young-Sam Lee
Department of New Biology, DGIST

Senescent cells exhibit a reduced response to intrinsic and extrinsic stimuli. This diminishedreaction may be explained by the disrupted transmission of nuclear signals. A proteomic
analysis of the cytoplasmic and nuclear fractions obtained from young and senescent cells
revealed disruption of nucleocytoplasmic trafficking（NCT）as an essential feature of replicative
senescence（RS）at the global level. Blocking NCT either chemically or genetically induced
the acquisition of an RS-like senescence phenotype, named nuclear barrier-induced senescence（NBIS）．A transcriptome analysis revealed that, among various types of cellular senescence,
NBIS exhibited a gene expression pattern most similar to that of RS. In addition, the global
transcriptomic downregulation of both the transcription-export（TREX）machinery and classicalnuclear localization signal（NLS）-dependent protein transport machinery was revealed invarious types of senescence. Core proteomic and transcriptomic patterns common to both RS
and NBIS included upregulation of the endocytosis-lysosome network and downregulation of
NCT in senescent cells, patterns also observed in an aging yeast model. These results imply
coordinated aging-dependent reduction in the transmission of extrinsic signals to the nucleus
and in the nucleus-to-cytoplasm supply of proteins and RNAs.
Keywords：Cellular senescence, Nucleocytoplasmic Trafficking, Nuclear Barrier－ 54 －Name：
Young-Sam Lee
Academic appointments：
DGIST, Daegu, South Korea
Associate Professor, Department of New Biology, DGIST（Sep. 2019～Present）
Assistant Professor, Department of New Biology, DGIST（Feb. 2016～Aug. 2019）
Education & Training：
Samsung Advanced Institute of Technology, Suwon, South Korea（Oct. 2013～Jan. 2016）
Senior Research Staff, with Dr. Sang Chul Park
National Institutes of Health, Bethesda, MD, USA（Sep. 2010～Sep. 2013）
Postdoctoral fellow, with Dr. Wei Yang.
University of Texas at Austin, Austin, TX, USA（Aug. 2004～Aug. 2010）
Ph.D. in Institute for Cellular and Molecular Biology
Seoul National University, Seoul, South Korea（Mar. 1997～Feb. 1999）
M.S. in Chemistry, with Dr. Jong-Sang Park
Seoul National University, Seoul, South Korea（Mar. 1993～Feb. 1997）
B.S. in Chemistry
Selected Publications：
1．Park SC＊, Lee YS＊, Cho KA, Kim SY, Lee YI, Lee SR, Lim IK. What matters in aging is signaling for
responsiveness. Pharmacol Ther.（2023），252：108560.（＊co-corresponding）
2．Woo SH, Mo YJ, Lee YI, Park JW, Hwang D, Park TJ, Kang HY, Park SC, Lee YS＊. ANT2 accelerates
cutaneous wound healing in aged skin via regulating energy homeostasis and inflammation. J Invest
Dermatol.（2023），143（11）：2295-2310.（＊corresponding）
3．Cho HJ*, Hwang JA, Yang EJ, Kim EC, Kim JR, Kim SY, Kim YZ, Park SC, Lee YS*. Nintedanib induces
senolytic effect via STAT3 inhibition. Cell Death Dis.（2022）13（9）：760.（＊co-corresponding）
4．Yang EJ, Park JH, Cho HJ, Hwang JA, Woo SH, Park CH, Kim SY, Park JT, Park SC＊, Hwang D＊, Lee YS＊.
Co-inhibition of ATM and ROCK synergistically improves cell proliferation in replicative senescence by
activating FOXM1 and E2F1. Commun Biol.（2022），5（1）：702.（＊co-corresponding）
5．Park JH, Ryu SJ, Kim BJ, Cho HJ, Park CH, Choi HJC, Jang EJ, Yang EJ, Hwang JA, Woo SH, Lee JH, Park
JH, Choi KM, Kwon YY, Lee CK, Park JT, Cho SC, Lee YI, Lee SB, Han JA, Cho KA, Kim MS＊, Hwang D＊,
Lee YS＊, Park SC＊. Disruption of nucleocytoplasmic traﬃcking as a cellular senescence driver. Exp Mol
Med.（2021），53（6）：1092-1108.（＊co-corresponding）－ 55 －

Changes in mitochondrial fusion and fission-related gene andprotein expression in AD transgenic mice
◦Anna Seino1, Takuma Hara1, Karin Toyooka2,
Taiki Nozawa2 and Koji Fukui 1, 2
1．Graduate School of Systems Engineering and Science, Shibaura Institute ofTechnology
2．Department of Bioscience and Engineering, College of Systems Engineeringand Science, Shibaura Institute of Technology

In recent years, the number of people with dementia has been increasing in Japan as the
population ages, and it is predicted that one in three elderly people will have dementia by 2060.
Alzheimer’s disease（AD）accounts for approximately 70% of dementia cases and significantly
reduces the Quality of Life（QOL）not only for patients but also for those around them, so early
detection and treatment development are urgently needed.
Mitochondrial（mit）dysfunction has been widely reported to be associated with the onsetof neurodegenerative disorders such as AD, but the detailed mechanisms remain unclear.
In our previous study, proteomic analysis using liquid chromatography-mass spectrometry/mass spectrometry（LC-MS/MS）revealed that the expression of mitochondrial-localized heatshock protein（HSP）60 changes before and after neurite degeneration. Furthermore, electron
microscopy revealed numerous morphological abnormalities in the mitochondria of neurites
treated with hydrogen peroxide. Mitochondria normally undergo repeated processes of fusionand fission to maintain their morphology and function（mitochondrial dynamics）．Because
neurite alterations are observed in the early stages of AD in the brain, we hypothesized thatneuronal dysfunction in AD may be due in part to the imbalance in fusion and fission mediatedby mitochondrial membrane oxidation by reactive oxygen species（ROS）．We analyzed
mitochondria dynamics-related proteins and genes. We used 4 and 12-month-old C57BL/6J miceas the control（Ctrl）group and age-matched heterozygous and homozygous 5xFAD mice as
the AD group. All mice were both male and female mice. After dissecting the mouse brain andhippocampus, we used reverse transcription quantitative polymerase chain reaction（qPCR）and
Western blotting to identify changes in gene and protein expression. Blood samples were alsocollected during dissection for serum testing. We confirmed changes in mitochondrial dynamicsrelated genes and proteins between some groups, and additionally observed differences basedon sex. Fusion-related genes increased in female mice compared to male mice, while divisionrelated proteins significantly increased in female mice compared to male mice. Therefore, it was
revealed that fusion and division of mitochondria may occur more frequently in females than inmales.
These findings suggest that mitochondrial dynamics dysfunction may be involved in the onset
and exacerbation of AD.
Keywords：Oxidative stress, AD, Mitochondria dynamics－ 56 －

〈 一般口頭発表 〉
６月 15 日（土）9：10～10：10

一般口頭発表Ⅰ-01～05

座長：水之江雄平（東京理科大学）
小林正樹（お茶の水女子大学）

10：15～11：15
座長：内田
嶋本

一般口頭発表Ⅱ-01～05

さえ（東京都健康長寿医療センター研究所）
顕（山口東京理科大学）

６月 16 日（日）9：00～10：00
座長：丸山
清水

光夫（国立長寿医療研究センター）
孝彦（国立長寿医療研究センター）

10：05～10：55
座長：三浦
木村

一般口頭発表Ⅴ-01～05

修一（順天堂大学）悠介（熊本大学）

13：20～14：35
座長：大澤
石井

一般口頭発表Ⅳ-01～04

ゆり（東京都健康長寿医療センター研究所）
展之（岡山理科大学）

11：00～12：15
座長：町田
小野

一般口頭発表Ⅲ-01～05

一般口頭発表Ⅵ-01～06

郁朗（東京都健康長寿医療センター研究所）
恭正（東海大学）

Ⅰ-01/ Y
Ⅰ-02/ Y・・S
Mixed antioxidant supplement improved the coordination Effects of Accumulated PARIS on Aging-related Diseases
ability of aged mice
○Hiroto Fukai1, Yuhei Mizunoe1, Yuka Nozaki1, Masaki Kobayashi2,3, Yoshikazu
Higami1,4
1. Laboratory of Molecular Pathology and Metabolic Disease, Faculty of
Pharmaceutical Science, Tokyo University of Science
2. Department of Nutrition and Food Science, Graduate School of Humanities andSciences, Ochanomizu University
3. Institute for Human Life Innovation, Ochanomizu University
Oxidative stress is known to be one of the factors that causes a decline in brain 4. Division of Cell Fate Regulation, Research Institute for Biomedical Science, Tokyo
functions such as cognitive function. One way to prevent this is to take of antioxidants University of Sciencesuch as ascorbic acid and coenzyme Q. Many studies focus on a single antioxidant.
However, taking multiple antioxidants may have more beneficial effects.
脂肪組織(WAT)は全身の代謝を制御する非常に重要な臓器であり、近年では
In this study, we investigated whether the administration of a multi-antioxidant アディポカインを分泌する内分泌器官としての役割が多数報告されている。肥
supplement to aged mice improves cognitive function. Male C57BL/6 mice aged 49 満や加齢により代謝状態が悪化すると WAT では細胞老化や慢性炎症が惹起さ
weeks were treated with a multi-antioxidant supplement (eight substances: ascorbic
れ、肝臓など非脂肪組織に異所性脂肪の蓄積などが引き起こすことが知られてacid, L-glutamine, L-cystine, niacin, succinic acid, fumaric acid, riboflavin, andcoenzyme Q10) dissolved in drinking water was administered ad libitum for 1 month. いる。当研究室では肥満マウスの WAT においてミトコンドリア生合成のマス
Body weight was measured once a week during the treatment period, and cognitive ターレギュレーターである PGC-1α(PPAR gamma coactivator 1 alpha)の発現がfunction and coordinated motor function were assessed at the end of the treatment period 低 下 す る こ と を 見 出 し た 。 そ こ で PGC-1 α の 発 現 抑 制 を 担 う 転 写 因 子
PARIS(Parkin interacting substrate)/ZNF746 に着目し研究を行った。PARIS は神using by the Morris water maze test and the Rota-Rod test.
Results showed that body weight, food and water intake did not change with 経細胞においてパーキンソン病の原因遺伝子 PARKIN の基質として同定されsupplementation. Behavioural experiments showed that only on day 4 in the water maze ているが、全身での局在解析の結果、特に WAT での発現が高かった。さらに、
test, the time to goal was significantly faster and the learning rate was significantly 肥満に伴い脂肪前駆細胞において PARIS タンパク質の発現が増加していた。
higher in the supplemented group compared to those of the controls. In the Rota-Rod
それゆえ、マウス脂肪前駆細胞である 3T3-L1 細胞に PARIS 過剰発現(OE)させtest, the supplemented group took longer to time-to-fall than the control group.
た
PARIS OE 細胞を作製し解析した。PARIS OE 細胞は脂肪細胞分化不全やミAlthough this experiment was conducted in 49-week-old mice for a short period oftime (one month), there was a trend towards improved cognitive function in the トコンドリア機能異常を引き起こし、細胞老化様の表現型を示した(Hachiya etsupplemented group, suggesting that the administration of a multi-antioxidant al., 2023)。以上から、本研究では老化における PARIS の働きを明らかにすることを目的とした。加齢に伴い WAT、特に脂肪前駆細胞において PARIS タンパ
supplement may be useful for improving brain function in mice.
ク質発現が増加していたことに加え、骨格筋や心臓といった複数の臓器でもKeywords: Oxidative stress, Antioxidant, Brain function
PARIS が蓄積していた。このことから PARIS が加齢によって WAT のみならず全身の複数の臓器で加齢病態に深くかかわっている可能性が示唆された。一
Related Articles:
方、加齢により増加した PARIS 蓄積を再現するため、3T3-L1 細胞にγ線照射
・J Clin Biochem Nutr. 72, 93-100, 2023
による細胞老化誘導を行ったが、PARIS の蓄積は観察されなかった。つまり、・J Clin Biochem Nutr, in press (Accepted Oct 2023)
単純な細胞老化誘導では PARIS の蓄積が起こらなかった。それゆえ、生体内での加齢による PARIS の蓄積には、複数の要因が関わっている可能性が示唆された。加齢による生体内での PARIS の蓄積機構を明らかにすることは加齢病態の理解に重要であると考える。

○Akari Nakamura1, Fukka You2, Haruhiko Inufusa2, Toshikazu Yoshikawa3, Koji
Fukui1
1. Shibaura Institute of Technology
2. Gifu University
3. Louis Pasteur Center for Medical Research

Keyword: PGC-1α, ZNF746 preadipocyte

Ⅰ-03/ Y・・S
Ⅰ-04/ Y・・S
Effect of dietary protein ratio on lipid metabolism in the Systemic and focal effects of the mitochondrial stressmouse liver
induced mitokine GDF15 in the adipose tissue○Jialin Chen1,2, Yuka Takino1, Shuichi Yanai3, Akihito Ishigami 1, Yoshitaka Kondo1
1. Molecular Regulation of Aging, Tokyo Metropolitan Institute for Geriatrics andGerontology
2. Tokyo Biotechnology Technical School
3. Animal Facility, Tokyo Metropolitan Institute for Geriatrics and Gerontology○ Tomoyoshi Fukuoh1, Yuka Nozaki1, Yuhei Mizunoe1, Masaki Kobayashi2,3,
Yoshikazu Higami1,4.
1. Laboratory of Molecular Pathology and Metabolic Disease, Facility of
Pharmaceutical Science, Tokyo University of Science
2. Department of Nutrition and Food Science, Graduate School of Humanities andScience, Ochanomizu University
3. Institute for Human Life Innovation, Ochanomizu University
4. Division of Cell Fate Regulation, Research Institute for Biomedical Science, Tokyo
University of Science[Background] We reported that the dietary protein ratio that maintains metabolic
health during approach to old age is 25-35% (Kondo et al., GeroScience, 45:2707-2726,
2023). In this study, we examined the effects of the dietary protein ratio on hepatic lipid
metabolism in young and middle-aged mice to determine the mechanism by which amoderate protein intake ratio suppresses hepatic lipid accumulation.
[Methods] Young (6-month-old) and middle-aged (16-month-old) male C57BL/6
mice were fed five diets with different protein calorie ratios (equal total calories; 25%
lipid ratio; 5%, 15%, 25%, 35%, and 45% protein ratio; and 70%, 60%, 50%, 40%, and
30% carbohydrate ratio) for eight weeks. After 3 h of fasting, the livers were harvested.
Lipid synthesis (Nr1h3, Nr1h4, Mlxipl, Srebf2, Gpam, Dgat1) and degradation (Ppara,
Cpt1a, Mcad), uptake (Fatp2, Fatp5, Vldlr), efflux (Abcg5, Abcg8, Mttp), energy
metabolism (Fgf21, Prkaa1, Prkaa2), and age-associated (p16Ink4a, p21, Tnf) gene
expression was analyzed by quantitative PCR (qPCR).
[Results] The expression of lipid synthesis (Nr1h3, Nr1h4, Mlxipl, Srebf2, andDgat1), degradation (Mcad), uptake (Fatp2, Fatp5, and Vldlr), efflux (Mttp), energy
metabolism (Prkaa1 and Prkaa2), and age associated (Tnf) genes was higher in the 5%
protein group and lower in the 35% protein group, regardless of age. Fgf21 expression
was highest in both young and middle-aged mice, and p21 expression was highest in
middle-aged animals in the 5% protein group.
[Discussion] The 5% protein (70% carbohydrate) group exhibited increased lipid
degradation, efflux, and energy expenditure, but increased lipid synthesis and uptake,possibly resulting in lipid accumulation in the liver. In contrast, the 35% protein (40%carbohydrate) group showed suppressed lipid accumulation, possibly by lowering lipid
synthesis and uptake. Furthermore, the protein ratio in the diet may affect aging.

White adipose tissue (WAT) plays an important role of energy storage as the form of
triglycerides and in the production of bioactive molecules, while brown adipose tissue(BAT) is involved in energy expenditure through thermogenesis. Mitochondria play a
key role in maintaining energy homeostasis in metabolic tissues including adipose
tissues. We recently found that adipose-specific mitochondrial intermediate peptidase(MIPEP) knockout (aMKO) mice, which are defective in mitochondrial protein
maturation, increased Growth differentiation factor 15 (GDF15) expression in
epididymal WAT (eWAT), BAT and plasma. GDF15, a mitokine, is induced via
mitochondrial unfolded protein response (UPRmt). However, the mechanism of GDF15
induction and the focal and systemic effects of GDF15 remain unclear. Therefore, we
analyzed aMKO and systemic GDF15 double knockout (DKO) mice to investigate theeffects of GDF15 induced by mitochondrial dysfunction in adipose tissue.
Compared to wild-type (WT) mice, aMKO mice had shortened lifespan. At 30 weeks,body weight remained unchanged, but aMKO mice exhibited lipoatrophy, BAT
whitening, and fatty liver. In both eWAT and BAT, MIPEP deficiency resulted in
mitochondrial proteostasis disorder and impaired adipocyte differentiation.
Furthermore, aMKO activated the UPRmt in both eWAT and BAT. In contrast to theaMKO phenotype, DKO mice had an even shorten lifespan. DKO did not alter bodyweight and lipoatrophy but exacerbated BAT whitening and fatty liver. In addition,
DKO did not affect mitochondrial dysfunction or adipocyte differentiation in either
eWAT or BAT, but attenuated UPRmt only in eWAT. The findings suggest that UPRmtinduced GDF15 may positively regulate the UPRmt as a focal effect in WAT and playa protective role in systemic metabolism.

Keywords: Aging, Macronutrient, Steatosis

Keywords: Adipose tissue, UPRmt, GDF15

1－ 58 －

Ⅰ-05/ Y・・S
Ⅱ-01/ Y・・S
Investigation of renal injury models with different MIPEP regulates adipocyte differentiation by
concentrations of adenine
maintaining the quantity and quality of mitochondria○Shunki Otomo1、Yuki Kanome1、Koji Fukui1○ Mamiko Ishimatsu1, Yuka Nozaki1, Yuhei Mizunoe1, Masaki Kobayashi2,3,
Yoshikazu Higami1,4
1. Graduate School of System Engineering and Science, Shibaura Institute of 1. Department of Pharmaceutical Science, Graduate School of Pharmaceutical, Tokyo
Technology
University of Science.
2. Department of Nutrition and Food Science Graduate School of Humanities and慢性腎臓病(CKD)は、腎機能が 3 か月以上かけて徐々に低下する疾患である。 Science, Ochanomizu University
CKD は進行すると末期腎不全となるが、現在有効な治療薬はない。その為、開 3. Institute for Human Life Science, Ochanomizu University
発が急務となっており、研究が世界各地で行われている。研究では通常、腎障 4. Division of Cell Fate Regulation, Research Institute for Biomedical Science, Tokyo
害モデル動物として 5/6 腎摘出モデルや db/db モデル、飼料誘発性モデルが用 University of Science
いられる。飼料誘発性モデルは発症時期や病態を制御できる利点があり、代表
The quality of white adipose tissue (WAT) is involved in the regulation of lifespan.
モデルとしてアデニンが用いられている。Ade 添加食(Ade)の濃度は 0.25、0.75%
Our previous research found that caloric restriction (CR) increased mitochondrialがほとんどであるが、ラットへの投与では、0.25%では腎機能以外に体重増加intermediate peptidase (MIPEP) expression in WAT with anti-aging and lifespanの抑制や摂餌量減少、0.75%では著しい体重及び摂餌量減少が報告されている。 prolonging effects (Kobayashi M et al., 2017). Most mitochondrial proteins are encoded
そこで我々は、より CKD モデルに最適なアデニン濃度の検討及びアデニンが in the nucleus, translated in the cytoplasm and then translocated to the mitochondria for
腎以外に与える影響の有無を検討した。
processing into the mature form. Although MIPEP-mediated mitochondrial protein
Wistar ラットに対照食(Ctrl)または、0.125、0.25、0.75、1.5%の Ade を与え飼 maturation has been suggested to be important for metabolic homeostasis in adipocytes
育した。飼育期間中は体重や摂餌量、尿量を測定した。その結果、体重は飼料 and lifespan regulation, the function of MIPEP remains unclear. Therefore, to elucidate
投与以降 Ctrl 群と比較し 0.25% Ade 群で増加を有意に抑制し、0.75、1.5% Ade the function and significance of MIPEP in the relationship between mitochondrial
群では有意に減少した。Ctrl 群と比較し解剖直前の摂餌量は、0.125%を除く全 homeostasis and adipocyte differentiation, we generated tamoxifen-inducible Mipepdeficient embryonic fibroblasts. We found that Mipep deficiency disruptedての Ade 群で有意に減少し、尿量は飼料投与以降全ての Ade 群で有意に上昇
mitochondrial proteostasis and impaired mitochondrial function in a time-dependent
した。また、尿中クレアチニン排泄量は Ctrl 群と比較して 0.125%を除く全ての manner. Furthermore, Mipep deficiency suppressed adipocyte differentiation,
Ade 群で有意に減少した。解剖後の血清 ALT 値は、Ctrl 群と比較し 1.5% Ade suggesting that MIPEP is important for metabolic homeostasis in adipocytes.
群でのみ有意に増加した。0.25% Ade 群では腎臓で炎症マーカーの発現量が Ctrl
群と比較し有意に上昇、逆に抗酸化酵素発現量は有意に低下していた。腎切片 Keywords: MIPEP, Mitochondria, Adipocytesの HE 染色では、0.25% Ade 群では尿細管に析出物が沈着、多数の萎縮した糸球体も確認した。
以上より、Wistar ラットへの 0.125% Ade では腎臓の再吸収能は低下するが、濾過機能には影響しない可能性がある。また、他のアデニン濃度では体重や摂餌量の減少など腎機能以外にも影響があること、更に 1.5% Ade では肝障害も誘発する可能性がある。今後は、0.125% Ade の長期投与や、0.125 以上 0.25%以下の濃度で同様の検討を行い、最適な CKD モデルの創出を目指す。
Keywords: 慢性腎臓病、腎障害モデル、アデニン

Ⅱ-03/ Y・・S
Ⅱ-02/ S
A novel type of astrocytes expressing Olig2 in mouse System xc-/xCT in microglia is a regulator of
dentate gyrus and their response to intermittent hypoxia neuropsychiatric disorder in vitamin E deficient mice
○Hidetoshi Nagamine 1, Yugo Kato1, Yosuke Horikoshi 1, Kazuhiro Nakaso 1
1. Tottori University, Japan○Shoichiro Omura1*, Rina Ogawa1*, Tomomi Kawachi1*, Natsumi Takayama1, Aya
Ogawa1, Yuuki Arai1, Hiroshi M Shinohara1, Tokiharu Takahashi1, Hideyuki Maeda2,
Kyoji Ohyama1*Equal contribution
1. Department of Histology and Neuroanatomy, Tokyo Medical University
2. Legal Medicine, Osaka University【Background】Long-term vitamin E deficiency (VE def) has been reported to cause
oxidative stress and to induce neuropsychiatric disorder. Recently, neuroinflammation
including activation of microglia has been focused in such an oxidative stress-related
pathogenesis. xCT, a component of cystine/glutamate antiporter System xc-. Although
microglial System xc-/xCT (xCT) uptakes cystine and enhances antioxidative capacity，
it releases glutamate to the extracellular space and induces excitotoxicity for surroundedneurons. We investigated the role of xCT of microglia in neuropsychiatric disorderunder VE def condition.
【Concluds】6-3 cells (cell line microglia) were cultured in serum-free advanced
RPMI1640 medium to mimic VE def. Under VE def condition, the expression of xCT
and the extracellular glutamate were increased compared to those in the VEsupplemented condition.
Wildtype (WT) and xCT-KO mice were fed VE def diet for 10 months andinvestigated their behaviors, biological and/or histological parameters. Behaviors
showed a cognitive decline in VE def mice, however, the disturbance in xCT-KO mice
showed milder symptoms than that in WT. microglial xCT is activated in long-term VE
def, suggesting the presence of inflammatory pathology. 4-HNE stain of the brain was
detected both in VE def WT mice and xCT-KO mice, suggesting that oxidative stressitself may not be a generator of cognitive decline and hypoactivity in this model.
These results suggest that it is the xCT-derived glutamate rather than oxidative stressthat exacerbates cognitive decline and hypoactivity in long-term VE def.

We have identified a novel type of astrocytes that express a transcription factor Olig2
in developing and adult mouse dentate gyrus (DG). We first show that, in addition to
Sox10+ oligodendrocyte progenitors (OLPs), Olig2 is expressed in gfap-GFP+
astrocytes but not NeuroD+ neuronal progenitors in the DG at E18-P14. Olig2+
astrocytes also co-express astrocyte markers BLBP/Fabp7 and Sox9 in postnatal mouse
DG. Intriguingly, the Olig2+ astrocytes also co-express NG2/cspg4, a marker for NG2
glia that are considered as either OLPs or reactive astrocytes. We then examined whether
the Olig2+/NG2+ astrocytes act as reactive astrocytes under the condition of intrauterineintermittent hypoxic injury (IH). Our data show that the number of Olig2+/Sox9+
astrocytes was increased under the IH condition, and that blood vessels became denser.
Neurovascular unit (NVU) is composed of astrocytes, blood vessels, and that its
dysregulation is associated with neurodegenerative diseases such as Alzheimer’s. Ourdata suggest that the NVU containing Olig2+/NG2+/BLBP+Sox9+ astrocytes exhibits
an adaptive response to the IH, thereby supplying blood flow in the DG.
Keywords: Olig2, Astrocyte, Neurovascular unit

Keywords: Vitamin E, xCT, neuropsychiatric disorder2－ 59 －

Ⅱ-04/ S
Ⅱ-05/ S
Co-expression of POMC and Prox1 delineates newly Cerebral blood flow responses to trigeminal olfactory
generated POMC neurons in the hypothalamus through stimulation and its nicotinic cholinergic regulation
lifetime
1,2
1,2
1
1
○Daichi Morihara , Jura Moriya , Fusako Kagitani , Sae Uchida
1. Tokyo Metropolitan Institute for Geriatrics and Gerontology
2. Tokyo University of Agriculture and Technology○Rina Ogawa1*, Aya Ogawa1*, Yuuki Arai1*, Shoichiro Omura1, Kumiko Kondo1,
Tokiharu Takahashi1, Hideyuki Maeda2, Kyoji Ohyama1*Equal contribution
1. Department. of Histology and Neuroanatomy, Tokyo Medical University
2. Legal Medicine, Osaka University

Olfactory dysfunction is an early symptom of Alzheimer’s disease (AD). Basal
forebrain cholinergic neurons, which degenerate in AD, project to the neocortex andolfactory bulb. Information about the sense of smell is conveyed by the olfactory nerve,
or by the trigeminal nerve when irritating odors. We recently reported that olfactory
nerve stimulation increases regional blood flow in the olfactory bulb, and the activationof nicotinic acetylcholine receptors (nAChRs) potentiates olfactory bulb blood flow
responses. This study aimed to clarify the effect of trigeminal olfactory stimulation on
cerebral blood flow and role of nicotinic cholinergic transmission.
Using anesthetized rats, regional blood flow in the olfactory bulb and frontal cortex
was measured with laser Doppler flowmetry or laser Speckle contrast imaging. Arterial
blood pressure was simultaneously recorded. Intranasal trigeminal nerve was stimulated
electrically. A nAChR agonist, nicotine, at a dose of 30 µg/kg was intravenously
injected.
Intranasal trigeminal nerve stimulation increased blood flow in both olfactory bulb
and frontal cortex with pressor response. In rats spinalized at the upper thoracic level,
the intranasal stimulation did not elevate blood pressure and olfactory bulb blood flow,
but increased blood flow in the frontal cortex. Intravenous injection of nicotine did not
influence the olfactory bulb blood flow but augmented the increased blood flow in thefrontal cortex following the intranasal trigeminal nerve stimulation.
These findings suggest that the olfactory information transmitted via the different
neuronal pathways, olfactory and trigeminal nerves, is processed in different regions in
the brain. Moreover, activation of nicotinic cholinergic transmission potentiates both
olfactory neural pathways.

Hypothalamus is a centre for endocrine and autonomic function and plays a key rolein maintaining homeostasis. Previous studies suggest that organismal ageing leads tothe dysregulation of homeostasis, consequently diseases such as diabetes and heart
failure. Proopiomelanocortin (POMC) neurons plays a key role in feeding behavior andenergy expenditure, thereby maintaining homeostasis. It is therefore assumed that
POMC neurons may prevent ageing process through the maintenance of homeostasis.
Emerging evidence suggest that POMC neurogenesis takes place in hypothalamus
from embryonic to postnatal period. However, it remains elusive as to how POMC
neurogenesis is regulated through lifetime. To address this question, we first performed
scRNAseq analysis of chick embryonic hypothalamus to elucidate the mechanism bywhich POMC neurogenesis is regulated in embryo. In combination withimmunohistochemistry, hybridization chain reaction, and ex vivo explant culture, ourdata show that Shh and Notch signalling converges to regulate POMC neurogenesis
through the regulation of Sox9, and that Notch inhibition leads to the increase of Prox1+
progenitors, promoting POMC neurogenesis. Our data also show that Prox1 is expressedin newly generated POMC neurons in postnatal/adult mouse hypothalamus. We are
currently investigating signals that would upregulate Prox1 expression, then promoting
POMC neurogenesis in postnatal/adult mouse hypothalamus.
Keywords: POMC, Hypothalamus, Neurogenesis

Keywords: Regional cerebral blood flow, Olfaction, Cholinergic system

Ⅲ-02/ Y
Ⅲ-01/ S
HIF-1α activation by fatty acid bound to albumin induces Role of plasma membrane phospholipid in cellularcell proliferation and senescence in renal proximal senescencetubular epithelial cells
11◯Kaori Kanemaru , Yoshikazu Nakamura
1. Department of Applied Biological Science, Faculty of Science and Technology,
Tokyo University of Science○Mio Narita1, Yoshifumi Kurosaki1,2, Ryota Miura1, Hakumei Chin1, Naokazu Sato1
Akemi Imoto1,2, Tsuneo Takenaka3, Takafumi Ichikawa1,2, Naohito Ishii1,2
1. Graduate School of Medical Sciences, Kitasato University
2. School of Allied Health Sciences, Kitasato University
3. School of Medicine, International University of Health and Welfare

Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a phospholipid predominantly
located in the inner leaflet of plasma membranes. It acts as a substrate for phospholipase
C, triggering the production of second messengers such as inositol 1,4,5-trisphosphateand diacylglycerol. These second messengers, in turn, initiate intracellular signalingcascades that modulate cellular processes like growth and proliferation. Furthermore,PI(4,5)P2 can be phosphorylated by class I phosphoinositide-3 kinase to generate
phosphatidylinositol 3,4,5-trisphosphate, a critical signaling molecule involved inregulating cell survival, proliferation, and migration. PI(4,5)P2 also plays a key role inregulation of various cellular functions including actin dynamics, endocytosis, andexocytosis through interactions with numerous binding proteins.
Our study revealed a decrease in the levels of PI(4,5)P2 in the plasma membrane,
following induction of cellular senescence. Moreover, chronic reduction of PI(4,5)P2
levels, achieved by overexpression of membrane-associated PI(4,5)P2-degrading
enzymes or downregulation of PI(4,5)P2-generating enzymes, led to several
characteristic phenotypes of cellular senescence. Additionally, our findings suggest thatoverexpression of PI(4,5)P2-generating enzymes attenuates cellular sensitivity tosenescence induction. Collectively, our results suggest a suppressive role of thePI(4,5)P2 in cellular senescence.

Background: Persistent proteinuria causes renal proximal tubular epithelial cells(PTECs) to accumulate albumin excessively and damages the renal tubules. Although
excessive albumin accumulation has been shown to induce cellproliferation andsenescence in PTECs, the detailed mechanism has not been clarified. Fatty acid boundto albumin was shown to increase hypoxia inducible factor (HIF)-1α expression in
PTECs. The aim of this study was clarifying the effect of HIF-1α activation by fatty acidbound to albumin on cell proliferation and senescence.
Methods: The cell line of human PTECs, RPTEC/TERT1, was treated with fatty acidbound to albumin (palmitic acid: Pal-alb, oleic acid: Ole-alb and arachidonic acid: Araalb). HIF-1α expression and the markers for cell proliferation (Ki-67) and senescence(p21, p16 and γ-H2AX) were analyzed using western blot, qPCR and
immunofluorescence. Additionally, we evaluated the effect of HIF activator(Roxadustat, ROX) on cell proliferation, dedifferentiation (Ets1 and Sox9), senescenceand fatty acid oxidation (FAO) in cells.
Results: In PTECs, Ole- and Ara-alb increased Ki-67, p21 and p16, whereas fatty
acid-free and Pal-alb showed no alterations. HIF-1α activation was observed bytreatment of only Ara-alb, suggesting that Ara caused cell proliferation and senescence
via HIF-1α activation. ROX treatment induced increase in the marker expression of
dedifferentiation and proliferation. Furthermore, ROX-treated cells showed the
reduction of FAO-associated gene expression, the accumulation of lipid droplet, andincrease in senescence markers.
Conclusion: Ara-alb induced excessive cell proliferation and following senescence
via HIF-1α activation. Furthermore, HIF-1α activation caused the defective FAO andlipid droplet accumulation, which may be associated with accelerated senescence of
PTECs.

Keywords: Phospholipid, Cellular senescence

Keywords: Senescence, HIF-1α, Fatty acid3

－ 60 －

Ⅲ-03/ Y・・S
Ⅲ-04/ YDNA damage induction by exosomes secreted from The Impact of senescent cells on the process of lungsenescent cells
regeneration: possible involvement of a nuclear receptor
signaling
1
2
1,2
3○ Yukihiro Ikegaki , Taiki Nagano , Tetsushi Iwasaki ,Kenji Miyado , Shinji
Kawada1,2
1. Department Biology, Graduate School of Science
2. Biosignal Research Center, Kobe University
3. Department of Cell Engineering, Center for Regenerative Medicine, Japan〇Mikako Hirose1, Hiromichi Tsushima1, Masataka Sugimoto1
1. Molecular and Cellular Aging, Tokyo Metropolitan Institute for Geriatrics andGerontology
Pulmonary emphysema is a major pathology of chronic obstructive pulmonary
disease (COPD) and is characterized by the destruction of alveolar walls. COPD is aleading cause of deaths worldwide; however there is currently no cure for the pulmonary
emphysema. Cellular senescence is accelerated in patients with COPD, and our previous
studies have shown that cellular senescence aggravates the emphysema-associatedpathologies in mouse models. Although the mechanism underlying senescence and
COPD remains largely unknown, we recently found that cellular senescence has
negative impact on the lung repair. In the present study, we analyzed the molecular link
between cellular senescence and lung repair in mouse emphysema model. Conditioned
media derived from senescent lung fibroblasts affected the differentiation of lungprogenitor cells, implying an effect of senescence-associated secretory phenotype(SASP) on the lung repair. We found that senescent cells suppress the activity of a
specific nuclear receptor through SASP, and administration of a synthetic agonist forthis nuclear receptor promoted alveolar regeneration and restored the respiratory
function in emphysema mice. While the involvement of the nuclear receptor in lungregeneration has not been documented, our RNA-sequencing analysis revealed its
activation in lung progenitor cells induced many genes categorized in tissue
development and morphogenesis. Among these genes, we focused on Wnt genes
because the loss or down-regulation of WNT signaling has been shown in patients with
COPD. We are currently investigating the interaction between this nuclear receptor andthe Wnt signaling pathway in lung regeneration.

Cellular senescence is defined as an irreversible cell cycle arrest. Senescent cells
accumulate with aging, and it has been reported from experiments using mice that theonset of senescence-related diseases is suppressed by removing senescent cells.
Therefore, research has been actively conducted to identify target proteins for
specifically removing senescent cells. We identified EPN3 as a gene whose expression
is elevated in a senescent cell-specific manner by comparatively analyzing gene
expression levels in senescent, normal, and apoptotic cells. Since the relationshipbetween EPN3 and cellular senescence was unclear, we conducted research aimed at
elucidating the molecular mechanism of cellular senescence through functional analysis
of EPN3.
When EPN3 was expressed in cells, we found that DNA damage was induced not
only in EPN3-expressing cells but also in surrounding non-EPN3-expressing cells.
Furthermore, treatment of cells with exosomes isolated from the culture supernatantinduced DNA damage, suggesting that EPN3-expressing cells induce DNA damage insurrounding cells via exosomes. It has been reported that DNA contained in exosomes(exoDNA) is involved in the induction of DNA damage (Ariyoshi et al., 2019), so we
isolated exoDNA from EPN3-expressing cells and treated it with normal cells by
lipofection, and found that DNA damage was induced. In addition, it has been reported
that oxidized DNA is mainly involved in the inflammatory response caused by DNA
damage (Geharke et al., 2015), so we expected that EPN3 might influence the oxidative
state of exoDNA. To verify the ability of oxidized DNA to induce DNA damage, vector
plasmids were oxidized by the Fenton reaction and introduced into normal cells, and asignificant increase in the amount of DNA damage was observed compared to controls.

Keywords: Cellular senescence, COPD, Lung regeneration

Keywords: Cellular senescence, Exosome, DNA damage

Ⅲ-05/ S
Ⅳ-01/ Y
Molecular basis of cellular senescence triggered by CDK Comprehensive analysis of age-related changes ininhibitiontranscriptome diversity by single cell RNA-seq data
analysis
12
1
2◯ Yuto Matsuo , Nagisa Isobe , Masahiro Takikawa , Makoto Hayashi , Fuyuki
Ishikawa2, Mahito Sadaie1,2
1. Tokyo University of Science
2. Kyoto University○Daigo Okada1
1. Center for Genomic Medicine, Graduate School of Medicine, Kyoto University,
Nanbusogo-Kenkyu-To-1, 5F, 53 Syogoin-Kawaramachi, Sakyo-ku, Kyoto 606-8507,
Japan

Senescence is a stress-responsive form of stable cell cycle exit. In our previous
exploration of compounds inducing senescence, we identified SU9516, a CDK inhibitor
primarily targeting CDK2. In our current study, we demonstrate that SU9516 induces
senescence in human diploid fibroblasts. Treatment with SU9516 resulted in theenlargement of nuclei and an increased population of cells with 4C DNA content,suggesting arrest at G2/M and G1 phase for diploid and tetraploid cells, respectively.
Notably, p53 accumulation occurred within hours of SU9516 treatment, although nodetectable DNA damage or expression of SASP factors accompanied this accumulation.
Furthermore, inhibiting ATM, a kinase involved in DNA damage response, did notaffect p53 accumulation. Treatment with a potent CDK2-specific inhibitor led to p53
accumulation comparable to that induced by SU9516 but did not induce senescence,indicating that CDK2 inhibition alone is insufficient for senescence induction. Cellularsenescence is typically triggered by genotoxic stresses, and the genotoxicity and NFκB-mediated SASP are recognized as detrimental aspects of therapy-induced
senescence. In this context, clarifying the molecular basis of SU9516-induced
senescence, characterized by reduced DNA damage response and SASP, could aid in
the development of less-detrimental therapeutic strategies utilizing cellular senescence.

Transcriptome data is a good resource of information to capture not only individual
gene expression, but also the overall state of the cells. Transcriptome diversity is aconcept that describes how diverse the genes are expressed in a sample. It is known tobe effectively utilized as a good feature of the overall transcriptome profile. Although
there have been studies that have examined aging changes in transcriptome diversity in
specific tissues and cell types, it has been unclear whether aging changes intranscriptome diversity are common phenomena among various cell-types or tissue orcell-type specific phenomenon. In this study, we analyzed the Tabula Muris Senis
dataset, a large public dataset of mouse single-cell RNA-seq for aging, tocomprehensively examine how intracellular transcriptome diversity changes with aging
in a variety of cell types. We found that some cell types increase, some do not change,and some decrease in transcriptome diversity with aging, respectively. In addition, thebiological functions of cells associated with transcriptome diversity were examinedusing gene set analysis, suggesting that it is associated with functions such as energy
metabolism. The results of this study demonstrate that age-related changes intranscriptome diversity are cell type dependent.

Keywords: Senescence, CDK, DNA damage response
Keywords: Transcriptome, Bioinformatics, Single cell RNA-seq

4－ 61 －

Ⅳ-02/ Y・・S
Ⅳ-03/ Y・・S
Lysine Specific Demethylase 1 (LSD1) suppresses cellular Effect of vitamin C deficiency on age-associated genes insenescence by epigenetically regulating Sirtuin-4 in a mouse liver
riboflavin uptake-dependent manner
1,2
1
2
1
○Taiichi Osumi1, Taiki Nagano2, Tetsushi Iwasaki1,2, Shinji Kamada1,2
1. Department of Biology, Graduate School of Science, Kobe University, Japan
2. Biosignal Research Center, Kobe University, Japan○ Yukari Mitsumaru , Ayami Sato , Koji Fukui , Akihito Ishigami , Yoshitaka
Kondo1
1. Molecular Regulation of Aging, Tokyo Metropolitan Institute for Geriatrics andGerontology
2. Department of Systems Engineering and Science, Shibaura Institute of Technology

Cellular senescence is defined as irreversible cell cycle arrest and is triggered bystresses such as DNA damage. We have recently identified SLC52A1, a riboflavintransporter, is upregulated in response to senescence-inducing stimuli and thensuppresses senescence. Riboflavin is known to be converted into flavin adenine
dinucleotide (FAD) which acts as a cofactor. We also found that elevation of
intracellular FAD levels due to increased expression of SLC52A1 is necessary for thesenescence suppression, but this mechanism is still unclear. It was reported that lysinespecific demethylase 1 (LSD1) is an enzyme that demethylates lysine 4 and lysine 9 ofhistone H3 in a FAD-dependent manner, and its dysfunction is leading to the promotionof senescence. Therefore, we analyzed the relationship between LSD1 activity and FAD
levels in suppressing cellular senescence.
In U2OS cells, depletion of LSD1 accelerated senescence induced by the anticancer
drug etoposide. Conversely, overexpression of LSD1 suppressed senescence in thisexperimental system. Moreover, demethylation of H3K4 and H3K9 was promoted bysenescence-inducing stimuli, suggesting that LSD1 is activated during senescence. In
addition, we clarified that demethylation of histone H3 was also induced byoverexpression of SLC52A1 and excessive addition of riboflavin to the medium, anddecreased the expression of senescence-promoting gene Sirtuin-4. Sirtuin-4 is a genethat is epigenetically repressed by LSD1 and has been reported to promote cellularsenescence by causing mitochondrial dysfunction. Importantly, inhibition of LSD1
decreased the senescence suppressive ability of SLC52A1. These results suggested that
increased uptake of riboflavin in response to senescence-inducing stimuli activated
LSD1 and suppressed cellular senescence by inhibiting Sirtuin-4 expression.

[Background] Previously, we demonstrated that vitamin C deficiency in mice resultsin shorter lifespans and various aging phenotypes. However, the relationship between
vitamin C deficiency and aging remains unclear. In this study, we investigated theeffects of vitamin C deficiency on the expression of age-associated genes in senescencemarker protein-30 knockout (SMP30-KO) mice that are unable to synthesize vitamin C
in vivo.
[Methods] Two-month-old SMP30-KO mice were divided into the following two
groups: vitamin C-sufficient group that was administered 1.5 g/L vitamin C water andvitamin C-deficient group that was administered 0.0375 g/L vitamin C water for six
months, and plasma and liver samples were collected. Body weight and food intake wereperiodically measured. Plasma and liver vitamin C levels were determined using highperformance liquid chromatography and an electrochemical detector. In addition, gene
expression in the liver was analyzed by quantitative PCR (qPCR).
[Results] The vitamin C-deficient group had a higher body weight than the vitamin
C-sufficient group. However, there were no differences in the food intake. The liver
weights in the female vitamin C-deficient group were higher than those in the vitamin
C-sufficient group. Vitamin C concentrations in the plasma and liver of the vitamin Cdeficient group were lower than those of the sufficiency group. The expression of ageassociated genes p16INK4a and p21 in the livers of both the male and female vitamin Cdeficient groups was higher than that in the vitamin C-sufficient group.
[Conclusion] Vitamin C deficiency in mice may promote aging in the liver.
Keywords: Age-associated genes, Liver, Vitamin C

Keywords: Cellular senescence, Riboflavin, Lysine-specific demethylase 1 (LSD1)

Ⅳ-04/ Y・・S
Ⅴ-01/ Y・・S
Effects of vitamin C on epigenetic modifications in C2C12 The impairment of chronic oxidative stress-induced
cells
autophagy causes sarcopenia with individual atrophy in
mice
1,2
1,2
1
3
○Tatsuki Minowa , Noritsugu Osakabe , Ayami Sato , Shuichi Machida , Akihito
Ishigami1,2, Yoshitaka Kondo1
1. Molecular Regulation of Aging, Tokyo Metropolitan Institute for Geriatrics andGerontology
2. Department of Biological Sciences, Tokyo Metropolitan University
3. Graduate School of Health and Sports Science, Juntendo University○Rikuto Toda1, Kayo Yasuda2, Takamasa Ishii3
1.Department of Applied Physics and Chemistry, School of Engineering, Tokai
University
2. School of Health Studies, Tokai University
3. School of medicine, Tokai University[Introduction] Vitamin C (VC) is involved in the regulations that converts 5methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) as a cofactor for DNA
demethylation enzyme (ten-eleven translocation: Tet). Recently, we found that VC
suppresses myogenic differentiation in murine myoblast C2C12 cells. However, theunderlying mechanism remains unclear. In this study, we aimed to elucidate themechanisms underlying the effects of VC on VC transporters and DNA demethylationin C2C12 cells.
[Methods] C2C12 cells showed suppressed proliferation under low-nutritional
conditions and promoted differentiation into myotubes. In this study, cells were cultured
in differentiation induction medium (DMEM+2% horse serum) containing 50 µM VC(VC+) or without VC (VC−) for 0-10 days. The culture medium was changed every day.
The VC concentrations in the cells were determined using high-performance liquid
chromatography (HPLC) and an electrochemical detector. Gene expression of the
reduced VC transporters SVCT1 and SVCT2 and the oxidized VC transporters Glut1,
Glut3, and Glut4 was analyzed by quantitative PCR (qPCR). 5-mC and 5-hmC levels
were quantified by dot blotting.
[Results] Intracellular VC concentration increased after VC addition, reaching a peakat 1 h. The expression of SVCT1 in the VC+ group was higher than that in the VC−
group on days 4, 8, and 10. The expression of SVCT2 in the VC+ group was higher thanthat in the VC− group at 10 days. In contrast, Glut1, Glut3, and Glut4 expression levels
did not differ between VC+ and VC− groups. 5-hmC levels in the VC+ group werehigher than those in the VC− group after day 4.
[Discussion] Suppression of muscle differentiation in C2C12 cells by VC may be due
to DNA demethylation by VC.

骨格筋は身体活動を行う上で必要不可欠であり、特に下肢の筋肉は歩行動作などで大きな役割を果たす。そのため、転倒や骨折などのリスクとなる加齢に伴う骨格筋重量低下(サルコペニア)に関するメカニズムを解明することは重要である。
本研究では、筋重量低下とオートファジー誘導の関連を検証するため、若齢(3-6 カ月齢)、中齢(12-15 カ月齢)、老齢期(26-30 カ月齢)の C57BL/6J マウスをもちいた。先ず、体重とヒラメ筋(赤筋)・足底筋(白筋)の筋重量の測定を行った。
その結果、個体萎縮が起きていないにも関わらず、加齢に伴ってヒラメ筋と足底筋の重量低下が認められた。さらに、オートファジー関連タンパク質抗体をもちいたウェスタンブロット解析を実施し、筋重量低下に伴ってオートファジ
ー誘導の亢進が示唆された。
先行研究において、ミトコンドリア電子伝達複合体Ⅱサブユニットをコードする SDHC 遺伝子変異によりミトコンドリアから活性酸素種を過剰産生する
Tet-mev-1 マウスの骨格筋では、ミトコンドリアの膨潤化(クリステの消失)によって筋線維構造が崩壊していることが見出されていた。そこで、我々は筋重量低下に伴って誘導されるオートファジーが、酸化ストレス障害を受けたミトコ
ンドリアを自食するミトファジーであると仮説した。Tet-mev-1 マウスのヒラメ筋と足底筋をもちいて、加齢に伴う筋重量低下とオートファジー誘導の関連を解析した。その結果、若齢期から慢性的な酸化ストレス下にある Tet-mev-1 マ
ウスでは、①加齢依存的に個体萎縮を伴う骨格筋重量の低下が生じる、②若齢期からオートファジー誘導が亢進している、③オートファジー誘導は若齢期と老齢期で変動なくピークアウトしている、ことを明らかにした。
また、エネルギー代謝におけるミトコンドリアの寄与は赤筋と白筋部位で異なることから、現在、ヒラメ筋と足底筋、および大腿四頭筋の赤筋と白筋部位の筋質解析を計画しており、その進捗状況についても可能な限り報告する。

Keywords: DNA demethylation, Myoblast differentiation, Vitamin C

Keywords: 骨格筋、オートファジー、酸化ストレス5－ 62 －

Ⅴ-02/ Y
Ⅴ-03/ SHox based positional identities influence myogenesis in Effects of aging and sex on ribosome biogenesis in theadult skeletal muscle
skeletal muscle○Ryosuke Okino1, Yuuki Gouda1, Yusuke Ono1,2
1. Muscle Biology Laboratory, Tokyo Metropolitan Institute for Geriatrics andGerontology
2. Department of Muscle Development and Regeneration, Institute of Molecular
Embryology and Genetics, Kumamoto University○Shota Fusen1, Yung-Li Hung1,2, Shuichi Machida1
1. Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan
2. Japan Society for the Promotion of Sciences, Tokyo, Japan【Background】Age-related muscle atrophy is characterized by deterioration of the fastrather than slow muscle fibers, the underlying mechanism of which is a reduction inmuscle protein, which further leads to changes in the contraction, synthesis, anddegradation of structural proteins of the muscle fibers. Furthermore, sex differences inage-related muscle atrophy are observed, when the rate of protein synthesis could be
dependent on ribosome biogenesis. However, studies have not focused on the effects ofaging and sex on the ribosomes (protein-synthesizing complexes) associated withmuscle atrophy. In this study, we investigated the effects of aging and sex on ribosome
biogenesis in the skeletal muscle.
【Methods】The fast-twitch plantaris muscles were collected from 6-, 12-, 18-, 24-, and30-month-old male and female F344 rats, and total RNA, muscle proteins, protein
synthesis signaling pathways, and ribosome biogenesis-related factors were analyzed.
【Results】In both male and female rats, the skeletal muscle mass and skeletal muscle
mass per body weight reduced on aging. However, the total RNA and 28S+18S rRNAof the skeletal muscle and indicator of ribosomal biosynthesis RPL10 protein levels
increased. The 4E-BP1 Thr37/46 phosphorylation and 4E-BP1 protein levels increased
due to aging in male rats, however, no significant age-related difference was observedin female rats.
【Conclusion】Our findings reveal age-related increase in the amounts of 28S and 18SrRNA in rat plantaris muscle. However, reduction in muscle protein levels was also
observed. The results suggest that the mechanism for reduction of muscle protein is
associated with a reduction in the efficiency of protein translation in male rats, however,no reduction in the efficiency of protein translation was observed in female rats.

Skeletal muscles are distributed throughout the body and its size and shape areanatomically and physiologically diverse, presenting a variety of functions such as
movement, respiration, articulation, facial expression, and mastication. We havepreviously described the body region-specific decline in the muscle mass with aging.
However, molecular basis underlying the positional specificities remains unclear. Here
we performed transcriptome analyses using a variety of muscles throughout the body togenerate a comprehensive atlas of mouse muscles and its stem cells (satellite cells) for
the region-specific gene expression profile. We described homeobox (Hox) genes as the
major region-specific genes based on embryonic origin and anatomical location, which
dictates satellite cell function in a regionally specific manner in adults, e.g., forced
expression of either Hoxc11, Hoxc12, or Hoxc13 resulted in precocious myogenic
differentiation ex vivo. Our results indicate that Hox based positional identities inmuscles should be considered for the development of efficient regenerative therapies formuscle diseases including age-related sarcopenia, potentially modulating regionspecific pathophysiology in adult muscles.
Keywords: Skeletal muscle, Sarcopenia, Positional identity, Hox

Keywords: Sarcopenia, Skeletal muscle, Ribosome

Ⅴ-04/ Y
Ⅴ-05/ Y・・S
Analysis of aged mice-specific abnormal muscle fibers Effects of AGEs on cellular senescence in C2C12 skeletal
reveals new insights into molecular mechanisms of muscle cells
sarcopenia
111〇Ryota Iyama , Tatsuya Hayashi , Tatsuro Egawa
1. Graduate School of Human and Environmental Studies, Kyoto University○Naoki Ito1, Takahiro Eguchi1, Nozomi Hayashiji2
1. Brain-Skeletal Muscle Connection in Aging Project Team, Geroscience ResearchCenter, National Center for Geriatrics and Gerontology
2. Center for Genomic and Regenerative Medicine, Juntendo University Graduate
School of Medicine

Introduction：終末糖化産物(Advanced Glycation End Products：AGEs)は、生体内で糖質とタンパク質が非酵素的に反応して生成され、加齢とともに蓄積する。本研究では AGEs が筋芽細胞の細胞老化に与える影響を明らかにすることを目的とした。
Method ： グリ セルア ルデ ヒド 由 来 AGEs(GA-AGEs) は 40 mg/mL BSA(inPhosphate buffer)にグリセルアルデヒド(GA)を最終濃度 0.1 M になるように添加し、37℃で 7 日間インキュベートして作成した。C2C12 細胞を播種し、コン
フルエントに達した時点で、GA(0.25, 0.5, 1.0 mM)もしくは GA-AGEs(0.5, 1.0,
2.0 mg/mL)を添加し 24 時間培養した。その後、SPiDER-βGal を用いてβgalactosidase(βGAL)活性を測定した。
Result：増殖 7 日目に刺激をした際は、0.5 mM GA 刺激では対照群(CON)と比較してβGAL 活性が有意に増加(p = 0.039, n = 6/group)したが、GA-AGEs 刺
激では有意な差が見られなかった。また、8 日目に刺激をした際には、1.0 mg/mL
GA-AGEs 刺激では CON と比較してβGAL 活性が有意に増加(p = 0.038, n =6/group)したが、GA に関しては 0.5, 1.0 mM において増加傾向が見られたものの有意な差は見られなかった。筋核数は、増殖 7 日目および 8 日目ともにいずれの群間においても有意な差は見られなかった。
Conclusion：増殖 7 日目および 8 日目に GA または GA-AGEs 刺激を行うこと
で、筋芽細胞の細胞老化を誘導する可能性が示唆された。

In a rapidly aging society such as Japan, the age-related decline in muscle mass andforce, sarcopenia, is an urgent medical and economic issue. However, the molecularmechanisms of sarcopenia are still largely unknown, and the molecules that are
responsible for the muscle weakness have not been identified. Using single muscle fiber
Ca2+ imaging analysis, we identified the presence of Ca2+-abnormal muscle fibers onlyin aged mice. The Ca2+-abnormal muscle fibers had a tubular aggregate-like structure
and morphologically abnormal mitochondria. Furthermore, a cluster of mitochondriarelated genes, including mitochondrially-encoded genes, were downregulated in Ca2+abnormal muscle fibers. We identified Ckmt2 and Perm1 as the molecules essential forthe expression of mitochondrially-encoded genes. The expression of Ckmt2 and Perm1
was downregulated in Ca2+-abnormal muscle fibers. Knockdown of Cktm2 or Perm1 by
AAV in vivo resulted in decreased expression of mitochondrially-encoded genes anddecreased muscle force, suggesting that reductions of Ckmt2 and Perm1 are responsible
for age-related muscle weakness. These results indicate that Ca2+-abnormal muscle
fibers are accumulated in aged mice, and that age-related mitochondrial abnormalities
and muscle weakness are caused by downregulation of Ckmt2 and Perm1.
Keywords: Sarcopenia, Abnormal fiber, Ca2+

Keywords: 終末糖化産物、細胞老化、筋芽細胞

6－ 63 －

Ⅵ-01/ Y・・S
Ⅵ-02/ Y・・S
Hydrogen rich water-induced thinning of mucus layer Enhancement effect of exercise training in mice treatedwith changes of bacterial flora in the small intestinewith deep-sea water extract-added water-treated mice
○Yui Ueta1,2, Akane Yokoyama1,2, Masumi Iketani1, Yasunori Fujita1, Masafumi Ito1,
Hideo Kawaguchi2, Ikuroh Ohsawa1
1. Biological Process Aging, Tokyo Metropolitan Institute for Geriatrics andGerontology
2. Graduate School Life Science, Toyo University.

○ Nagisa Tomioka1, Syuya Yuzawa1, Masahiro Kohno1, Nozomu Takeuchi2,
Hirotsugu Takenaka2, Koichi Takenaka2, Koji Fukui1,
1. Graduate School of System Engineering and Science, Shibaura Institute ofTechnology
2. DyDo-Takenaka Beverage Co., Ltd.

Drinking of hydrogen-rich water (HW) alleviates many diseases, which may be
mediated by homeostasis of the small intestinal immune system. We reported previouslythat HW suppresses both antigen absorption and dendritic cell (DC) activation in thePeyer's patches (PP) of mouse small intestine. The intestinal mucus barrier might bemodified by HW. Mucin, a major mucus component, is secreted by goblet cells anddegraded by Akkermansia muciniphila. We then investigated the effect of HW on the
mucin layer.
Methods: HW was administrated by gastric gavage once to mice. After 1–6 h,contents in the small intestinal tract were collected, and mucin and intestinal bacteria
were quantified with colorimetric method and RT-PCR, respectively. Muc2 in fresh
frozen sections of the ileum PP was immunostained. To confirm A. muciniphila as ahydrogen bacterium, fresh feces were incubated in H2-bubbled medium for 2 h.
Results: The amount of mucin in the intestinal tract decreased 6 h after HWadministration. We also confirmed that the Muc2 positive mucin layer was thinner andrelative increase of A. muciniphila was observed 1 h after HW administration. Similarly,
A. muciniphila in feces was grown in anerobic H2-saturated media.
Discussion: This is the first report that HW administration decreases the intestinal
mucin. Because of the suppressive effect of HW on antigen absorption, we initially
expected thickening of the mucin layer. Since A. muciniphila, a hydrogen bacterium, isknown to suppress DC activation, HW-induced activation of this mucinolytic bacteriumis under investigation.

近年、すべての年代でミネラル摂取が不足している。ミネラルの供給源には食事からサプリメントまで様々な方法があるが、我々は海洋深層水に着目している。海洋深層水は Mg や Ca 等の多種多様なミネラルを多く含むことから、利用に注目が集まっている。先行研究ではマウスへの投与により、肥満や脂肪肝の軽減が示唆されている。しかし、それ以外の効果については不明な点が多い。
そこで本研究では、マウスに高脂肪高スクロース食(HFSD 食)を給仕して肥満や高血糖を誘導し、海洋深層水から抽出したミネラルの濃縮物(いわゆる「にがり」)を添加し、硬度を調整した水(DSW)を投与した。投与期間終了後にトレッドミル装置を用いた運動トレーニングを行い、肥満に対する減量効果やトレーニングによる持久力向上効果について検証した。
10 週齢の C57BL/6J 雄性マウスに HFSD 食を 10 週間給仕した。通常群には浄水器に通した水道水、DSW 群として硬度 300 に調節したにがり添加水を与えた。給仕 8 週間後にトレッドミル装置を用いて持久力試験を行った。その結果に基づき、運動能力が均等になるようにマウスを 4 群に分け、トレーニング
群には 2 週間の運動トレーニングを実施、トレーニング後に 2 回目の持久力試
験を実施した。試験後に解剖して採血を行い、各種マーカーを測定した。
その結果、DSW 投与はトレーニング中の体重増加を有意に抑制した。DSW
投与群間では、トレーニング実施群で非実施群と比べ、2 回目の持久力試験で走行距離が有意に増加した。さらに同群間での比較では、肝機能マーカーである AST、ALT の値が有意に減少した。このことから海洋深層水由来にがり添加
水の継続飲用は、肥満予防、持久力向上、肝機能改善効果に有効な可能性がある。

Keywords: Akkermansia muciniphila, Mucin, Peyer's patches

Keyword: 海洋深層水、ミネラル、運動トレーニング

Ⅵ-04/ Y・・S
Ⅵ-03/ Y
Effects of glucosamine on human colonic microbiota in an The Effects of Tocotrienols on Mice Pre-Fed on a HighFat Dietin vitro model◯Tomoya Shintani1, Daisuke Sasaki1, Akihiko Kondo1
1. Kobe University【目的】グルコサミンは、関節をサポートするサプリメントとして世界的に利用されているが、その関節への効果については懐疑的な報告も多い。近年、欧州における大規模な疫学研究により、関節への効果に関係なくグルコサミン
摂取がヒトの死亡率の低下に寄与していることが報告されている。また実験動物においては、グルコサミン摂取による糖代謝の改善効果やオートファジーの誘導効果が確認されており老化を遅延する効果が報告されている。一方で、経口摂取したグルコサミンは、その約半分量が上部消化管に吸収されるが、吸収を免れた残りの約半分量が大腸に到達することが報告されている。しかし、宿主であるヒトの健康に寄与する大腸内細菌叢に対するグルコサミンの影響に関する報告は非常に限られている。そこで、本研究ではヒトの大腸内に生息する腸内細菌叢やその代謝物を in vitro 培養で模擬できるヒト大腸内細菌叢モデル(Kobe University Human Intestinal Microbiota Model; KUHIMM)を用いて、グル
コサミン添加がヒト大腸内細菌叢に及ぼす影響を解析した。
【方法・結果】13 名の健康なヒトの糞便をそれぞれ接種源として KUHIMM
にて培養を開始した。培養開始 24 時間後にグルコサミンを 0.2%(w/v)または
0.5%ずつ添加した。培養開始 72 時間後(グルコサミン添加後 48 時間後)まで培養し、培養液を回収して、上清の短鎖脂肪酸の産生量や菌体の菌叢構造について、非添加培養系と比較した。その結果、0.5%グルコサミンの添加によって、短鎖脂肪酸の総量に変化はなかったが、酢酸の産生が減少した一方で、酪酸の産生が増加した。なお 0.2％グルコサミン添加でも同様の傾向が確認された。
次に培養菌体から DNA を抽出して次世代シーケンサーにより 16S rRNA 遺伝
子解析を行い、菌叢の多様性を解析したところ、グルコサミン添加によって多様性指数に変化はなかった。また菌叢構造を解析したところ菌叢構造自体には明らかな影響を与えなかったが、0.2%および 0.5%グルコサミン添加により、
Anaerostipes 属(酪酸産生菌)の相対占有率が増加することが確認された(p < 0.05,
Wilcoxon matched-pairs signed rank test)。最後に、0.5%ずつ種々の単糖類を含む培地で Anaerostipes を 24 時間培養して、短鎖脂肪酸の生産量を測定したとこ
ろ、酪酸の生産量はグルコサミンを添加した場合に最も高いことが確認された。
【結論】グルコサミンは、ヒト大腸細菌叢モデルにおいて Anaerostipes 属を選択的に増加させて、宿主に対して有益な効果を有する酪酸を産生した。

○Shuntaro Richard Kashiwaya1, Junhyeok Byeon1, Hayate Suzuki2, Koji Fukui1,2
1. Graduate School of System Engineering and Science, Shibaura Institute ofTechnology
2. Department of System Engineering and Science, Shibaura Institute of Technology
Obesity is a modern health epidemic in countries around the world, and can lead tovarious diseases such as type 2 diabetes, cardiovascular diseases, and dementia. Our
previous study showed that tocotrienols (T3), a type of vitamin E with potent antioxidant
properties, reduced weight gain and obesity-induced brain oxidation in mice fed highfat diet (HFD). To further elucidate the anti-obesity properties of T3s, we investigatedwhether T3s could attenuate body weight gain and obesity-induced cognitive
impairment in mice pre-fed with HFD. The experiments were conducted by distributing
10-week-old male C57BL/6 mice to a control diet (Ctrl), HFD, HFD with 0.05% T3mix (T3s+0wk), and HFD+T3s after 8 weeks of a HFD (T3s+8wk). The mice weretreated for 16 weeks, and their body weight, food intake, and water intake were
measured once a week. After the feeding period, cognitive function was measured with
the Morris water maze test and their resting energy metabolism and locomotor activity
were measured using Oxymax○R and ACTIMO systems. The mice were then dissected,
and their organs and adipose tissues were collected. As a result, both T3s+0wk and8wk+group tended to have a lower body weight gain compared to the HFD group, but
the difference was not significant. The Morris water maze test showed no significant
differences in their cognitive function with or without T3s. When measuring the restingenergy metabolism, there were no significant differences in the respiratory exchange
ratio when comparing all HFD groups. However, the locomotor activity wassignificantly higher in the T3s+8wk group when compared to the HFD and T3s+0wk
group. These results showed that intake of T3s may have an anti-obesity effect after
obesity.
Keywords: High-fat diet, Tocotrienols, Anti-obesity

Keywords: Glucosamine, Human colonic microbiota, Butyrate

7－ 64 －

Ⅵ-05/ Y・・S
The effects of royal jelly on stem cell aging

Ⅵ-06/ Y
Senomrphic effect of royal jelly in epidermal keratinocyte◯ Yukie Kande1, Yasuaki Ikuno1, Nobuaki Okumura2, Hideto Okamoto2, Manabu
Shirai3, Dai Ihara1, Yu Katsuyama1, Hayato Kaneda1
1. Shiga University of Medical Science
2. Yamada Bee Company, Inc.
3. National Cerebral and Cardiovascular Center○Yukie Nakagawa1, Hideto Okamoto1, Takashi Ito1, Nobuaki Okumura1
1. Yamada Bee Company, Inc.
Royal jelly (RJ) is a honeybee’s product that people have used for their health as anapitherapy since ancient times. RJ has lately been used in cosmetics and supplements tomaintain skin health. Recent studies have demonstrated that RJ is a valuable material
for protecting against skin aging. We have shown that RJ protects against epidermal
stress via activating anti-oxidant agents. However, its effect on senescent cells itself has
not been unveiled. In this study, we explored the effect of RJ on aged skin by using
senescence keratinocytes. We generated a replicative senescence model from primaryneonatal human keratinocytes with repeated passage. We confirmed that increase in
known senescence markers, such as senescence-associated β-galactosidase-positive
cells and expression of p16 and p21, in the senescence keratinocytes. Therefore, we
treated 1 mg/mL RJ for 24 hours on senescence keratinocytes, and then RNAsequencing was performed. We identified the downregulation of genes related tosenescence-associated secretory phenotype (SASP) factors such as IL-6, CXCL-5 andPAI-1 in RJ-treated senescence keratinocytes. We confirmed the decrease in thesecretion of IL-6 in the culture supernatants by ELISA. In addition, RJ downregulated
the expression of TGF-β receptors, which modulate SASP secretion and senescencephenotypes. These results suggested that RJ is a senomorphics material useful in skinaging.

Royal Jelly (RJ) is widely ingested as a health food, and recent studies have shownthat RJ and its unique component, 10-hydroxy-2-decenoic acid (10H2DA), havebeneficial effects on various diseases such as geriatric diseases, metabolic disorders, andinflammation. However, little is known about the molecular mechanisms underlying theRJ efficacy and its effects on stem cells. Therefore, we aimed to elucidate the effects of
RJ on stem cell aging and its molecular mechanisms both in vitro and in vivo byadministering RJ to human mesenchymal stem cells (MSCs) and aged mice. We
investigated genes whose expression levels were altered by RJ administration to MSCs
by RNA-seq and identified a candidate RJ target gene. The expression level of this gene
was decreased in old mice and was strongly upregulated by RJ administration, especiallyin the liver. Administration of RJ to old mice suppressed gray hair, reduced F4/80positive macrophages (MΦ) in the intestine, and induced neurogenesis in the brain withan increase in neural stem/progenitor cells. We are investigating whether these effects
are due to 10H2DA. Although the function of candidate RJ target gene is largely
unknown, its involvement in the differentiation and activation of anti-inflammatory
M2MΦ has been reported. Therefore, RJ may exert multiple effects in various tissues
due to its anti-inflammatory effects via induction of M2MΦ.

Keywords: Royal Jelly, Cellular Senescence, SASP

Keywords: Royal jelly, Stem cell aging, 10-hydroxy-2-decenoic acid8

－ 65 －

〈 一 般 ポスター発表 〉
６月 15 日（土）会場：大講義室前ホワイエ（Foyer）
掲示締め切りポスター討議撤収締め切り

11：45

12：15～13：30

６月 16 日（日）15：00

P-1
Age-related changes in the muscle characteristics offorelimb and hindlimb of senescence accelerated mouse
P8 and R1 strains〇Keiko Odera1, Risa Honnami1, Ryoya Takahashi1
1. Department of Biochemistry, Faculty of Pharmaceutical Sciences, Toho University
Senescence accelerated mouse (SAM), a murine model of accelerated senescence,
was established by Toshio Takeda and colleagues. The short-lived SAMP8 is useful for
pharmaceutical Intervention studies for treatment of sarcopenia. For this purpose,accurate capture of age-related change in muscle strength and muscle quantity/quality
is very important. The muscle strength of mice is usually determined by using the pole
grip test (PGT), mesh grip test (MGT) and grip strength test (GST). Although theforelimbs have a significant impact on performance in these tests, little research has
been done on age-related changes in forelimb muscles. In this study, we investigated therelationship between muscle strength and quantity/quality of the forelimb and hindlimb
muscles of different aged SAM.
Male SAMP8/Toho and SAMR1/Toho were used in our experiment. After measuring
muscle strength (PGT, MGT, GST), dissection was performed under isoflurane
anesthesia, and 5 types of muscles (triceps, etc.) from the forelimbs and 6 types ofmuscles (gastrocnemius, etc.) from the hindlimbs were extracted, and their wet weights
were measured. After measurement, neutral formalin fixation was performed. The size,
number, and area of myofibers were measured using HE staining of cross sections ofeach muscle.
No difference was observed in PGT and GST scores between the two strains, but
MGT score was lower in SAMR1 than SAMP8. Furthermore, there was no difference
in relative muscle mass per body weight between the two strains except for the soleus
muscle. The similar results were observed in the forelimb muscle. In addition, no
apparent difference was observed in the total fiber number, muscle fiber cross-sectionalarea, and total muscle fiber cross-sectional area of the triceps brachii and gastrocnemius
muscles of both strains. We are planning to analyze the muscle fiber types of forelimband hindlimb of both strains.

P-2
Age-related changes of Tau in cat brain○Nobuyuki Kimura1, Ikuyo Zukeyama1, Miaoyan, Zhang1, Fumio Hoshi2, Yumi Une3
1. Department of Veterinary Associated Science, Faculty of Veterinary Medicine,
Okayama University of Science (OUS)
2. Department of Internal Medicine I, Faculty of Veterinary Medicine, OUS
3. Department of Pathology, Faculty of Veterinary Medicine, OUS
It is widely accepted that the progression of Tau pathology is the key event for
Alzheimer’s disease (AD) onset, however, it remains unclear how aging induces Tau
pathology. In feline brain, age-related Tau pathologies are observed. Previous study also
showed that Tau pathologies in domestic cat are homologous to AD patient. In thepresent study, we examined biochemical analyses of Tau in brain from young (2-yearold [N=3], 5-year-old [N=2], 6-year-old {N=1}) and aged (12-year-old [N=1], 15-yearold [N=1], 17-year-old [N=1], 18-year-old [N=1], 19-year-old [N=1], 24-year-old[N=1]) domestic cats. Tris-soluble Tau levels were strongly increased in aged cat brains
except 18-year-old cat. On the other hand, sarkosyl-insoluble Tau was observed only inthree cat brains (15-, 17-, and 19-year-old). Accumulating evidences suggest that thealterations in protein degradation system can cause intracellular accumulation of
insoluble Tau. However, we could not find any correlations in those three cat brains.
Previous study showed that intracellular Tau is incorporated into multivesicular bodies(MVBs) and then degraded via fusion with lysosome. Noteworthy, the levels of
TSG101, which regulates MVB formation, were clearly dropped in the three cat brains.
We also confirmed that the knockdown of TSG101 induced intracellular accumulationof cat Tau in neuronal cell line. These findings suggest that the downregulation of
TSG101 would be involved in the formation of age-related Tau pathology in cat brain.
Keywords: Cat brain, Tau, TSG101

Keywords: Senescence-accelerated mouse, Muscle, Sarcopenia

P-3
Renal function in aged C57BL/6J mice. Age-related
apolipoprotein A-II amyloid deposition impaired thefunction independently of kidney aging○Hiroki Miyahara , Ying Li , Jian Dai , Akihito Ishigami , Masayuki Mori , Keiichi
Higuchi1, 3
1. Shinshu University,
2. Tokyo Metropolitan Institute of Gerontology,
3. Meio University
1

1

1

2

1

Spontaneous and age-related systemic amyloidosis has been reported in C57BL/6J
mice; however, the biochemical and pathobiological characteristics of age-related
amyloidosis remain unclear. We investigated the age-related prevalence of amyloidosis,
the types of amyloid fibril proteins, and the effects of amyloid deposition on renal
function. Male C57BL/6J mice, aged 8 to 86 weeks, were supplied by Charles River
Laboratories/The Jackson Laboratory Japan, the animal facility at the Tokyo
Metropolitan Institute of Gerontology and Japan SLC. The results obtained revealed ahigh incidence of systemic amyloidosis in C57BL/6J mice as well as the deposition oflarge amounts of amyloid in the glomeruli of aged mice. We identified that the amyloid
fibril protein in C57BL/6J mice is wild-type apolipoprotein A-II (AApoAII). We
induced renal amyloid deposition by injection of a small amount of amyloid fibrils inyoung mice, equivalent to that of spontaneous heavy development in 80-week-old mice,to rule out the effects of aging, and revealed subsequent damage to kidney function byamyloid deposits. Furthermore, amyloid deposition in the mesangial region decreased
podocyte density, compromised foot processes, and led to the accumulation of fibroblast
growth factor 2 (FGF2) in glomeruli. Medin, a Lactadherin (MFG-E8) co-deposited
with AApoAII amyloid in the kidneys. Collectively, these results suggest that AApoAII
deposition is a general pathology in aged C57BL/6J mice. Therefore, the effects of agerelated amyloid deposition need to be considered in research on aging in mice.
Keywords: Mouse, Amyloidosis, Kidney

P-4
Assessment of chronologicalintervention in healthy dogs

aging

and

longevity○Takashi Ito1
1. RIKEN CSRS
In aging research, several strategies have been identified to prolong the lifespan ofmodel organisms under laboratory conditions. Yet, the applicability of theseinterventions in real-world settings remains unproven. The challenge of translating
findings from aging research into practical health benefits is exacerbated by the fact thataging is not conventionally targeted by medical treatments, and the inherently lengthy
human lifespan. While environmental factors associated with longevity have beenrecognized, the specific impact of biotic components within the human environment onlifespan has not been fully explored in either humans or laboratory models. This study
introduces domestic dogs as a novel mammalian model to study aging within anenvironment akin to human living conditions, aiming to uncover biomarkers associatedwith healthy aging. Through bi-annual comprehensive evaluations, including blood
molecular analysis, gut microbiome profiling, and phenotypic assessments likeechocardiography, we identified several biomarkers that undergo significant changes
over six-month intervals. Crucially, we discovered that a bacterial strain, P-1, prevalentin human habitats, notably extends the lifespan across various eukaryotic models,
including budding yeast, nematodes, and both short-lived and wild-type mice of both
sexes. This effect appears to be mediated by the inhibition of the mTORC1 pathway, amechanism conserved across these species. Administration of the P-1 strain to pet dogs
revealed similar blood RNA-Seq profiles to those observed in P-1-treated mice,indicating mTORC1 pathway suppression. Moreover, chronological aging markers indogs were significantly reversed in the P-1 treatment group. These findings underscorethe potential of pet dogs as a valuable model for aging research, suggesting that specificmicrobiota could play a pivotal role in modulating longevity in eukaryotes.
Keywords: Pet dogs, Chronological aging, Bacteria－ 68 －

P-5
Why do mice fed egg only diet live healthy?

P-6
Role of hippocampal microglia in anxiodepressive-likebehaviors of aged mice

○Naomi Nishio1, Ken-ichi Isobe2
1. Department of School Health, Faculty of Education, Saitama University,
2. Department of Medical Technology, Faculty of Medical Sciences, Shubun University○Yoki Nakamura1, Miku Yokohata1, Keisuke Ikeda1, Kazue Hisaoka-Nakashima1,
Yukio Ago2, Ayami Sato3, Akihito Ishigami3, Norimitsu Morioka1
1. Department of Pharmacology, Hiroshima University【背景】鶏卵は糖質が極端に少なく、脂質が約 60%でコレステロールを多く
2. Department of Cellular and Molecular Pharmacology, Hiroshima University
含んでいる。しかし、鶏卵のタンパク質はアミノ酸組成が人の健康維持に理想 3. Molecular Regulation of Aging, Tokyo Metropolitan Institute for Geriatrics and的であり、多くのビタミン、ミネラルを含んでいる。私たちはこの学会で、鶏 Gerontology
卵のみ摂取させたマウスが１年半以上、健康な状態で生きることを示した。さThe relationship between age-related alterations in cellular function and theらに、それらマウスの肝臓の組織と血清生化学を測定したところ正常な肝臓であった。鶏卵と同じ濃度(60%)の脂質でも脂肪肝を発症することが報告されて pathogenesis of central nervous system diseases in older adult remains unclear.
おり、私たちの実験でも 60%高脂肪食でマウスは脂肪肝を発症させることを確 Microglia are immune cells that maintain brain homeostasis. Recent studies havereported that aging influences the microglial function in the brain. Therefore, the present
かめている。それでは、なぜ鶏卵のみで脂肪肝が１年半以上発症しないのか。
study examined the relationship between microglia and anxiodepressive-like behaviors
本報では極端に少ない糖質に着目して実験を行った。【方法と結果】1)まず初 in aged mice.
めに、鶏卵にはほとんど糖質が含まれていないことから、糖質が脂肪肝を誘導
Social interactions such as sniffing, grooming, and following behaviors was
し易いことを示す実験を２ヶ月齢のマウスを用いて行った。その結果、高脂肪 significantly reduced in aged mice (24 month-old) compared with young mice (3 month食(60%脂質と糖質を含む)では脂肪肝の誘導に数か月要したにも関わらず、糖 old). In addition, aged mice tended to take a longer latency to feed on a novel質(グルコース、フルクトース、砂糖)のみを投与すると１ヶ月で脂肪肝が発生 environment. These findings indicate that normal aging develop anxiodepressive-like
した。2) 糖質投与１ヶ月後に鶏卵のみ投与すると、脂肪肝は回復して正常の肝 behaviors. Hippocampus is a crucial brain region in the pathogenesis of depression and臓に戻った。一方で、普通食の投与でも脂肪肝の改善が見られた。【考察】鶏 anxiety disorders as well as cognitive dysfunction. Therefore, we evaluated the cellularsenescence of microglia in the hippocampus. Aged mice showed the p16INK4a-positive
卵にはコリン、メチオニンが通常よりも多く含まれている。コリンやメチオニ
microglia was increased compared with young mice. Furthermore, the cell territory ofンの欠乏は脂肪肝を誘導することが示されているため、これらの栄養素が脂肪 microglia was also reduced in aged mice. These data suggest that normal aging induces
肝を抑制していることが考えられた。しかし、通常量のコリン、メチオニンが cellular senescence of hippocampal microglia and may influence the microglial
含まれている普通食の投与でも脂肪肝が改善されたことから、鶏卵のコリン、 function.
メチオニン高含量が要因とは考えにくい。鶏卵のみ与える飼育は、ほぼ糖質ゼ
The present study clarify that functional alterations of hippocampal microglia
ロの栄養素で飼育することに近い。従って糖質の有無に関係なく、完璧なアミ associated with cellular senescence may be related to the pathogenesis of
ノ酸組成のタンパク質や、脂肪、ビタミン、ミネラルなどの栄養素が、長期間 anxiodepressive-like behaviors in old age. Further investigation based on these findings
could identify new drug targets for anxiety and depressive disorders in the older adult.
の肝機能維持に必要であることが予想された。
Keywords: Anxiety, Microglia, Senescence

Keywords: 脂肪肝、鶏卵、糖質

P-8
P-7Regular voluntary exercise increases NAD+ levels and Muscle-Derived Seno-Suppressor: Unraveling the Novel
cognitive function in aged mice
Link to Exercise Therapy◯Jimmy Kim1, Jonghyuk Park2, Ko Yamanaka1, Shuichi Machida3, Hidefumi Waki1,4
1. Department of Physiology, Graduate School of Health and Sports Science, Juntendo
University, Chiba, Japan
2. Neural Development Project, Department of Brain Development and Neural
Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
3. Department of Exercise Physiology, Graduate School of Health and Sports Science,
Juntendo University, Chiba, Japan
4. Institute of Health and Sports Science & Medicine, Juntendo University, Chiba, Japan◯Hiromichi Tsushima1, Azusa Asai2, Tohru Hosoyama2, Hirobumi Tada2,3, Mikako
Hirose1, Atsushi Watanabe2, Masataka Sugimoto1,2
1. Tokyo Metropolitan Institute for Geriatrics and Gerontology
2. National Center for Geriatrics and Gerontology.
3. Shigakkan University
Senescent cells contribute to tissue aging and underlie the pathology of chronic
diseases. Elimination of senescent cells exerted beneficial effects in several diseasemodels and in human pathologies. Exercise has been shown to reduce the cellularsenescence in multiple tissues, while its mechanism largely remains unknown.
In the present study, we investigated myokines that potentially mediate the antisenescence activity of exercise training. We found that cellular senescence wassuppressed in mouse embryonic fibroblasts (MEFs) cultured in the presence of myocyte(C2C12)-derived conditioned medium (CM). Mass spectrometry analysis of the C2C12CM revealed several factors of these serum concentrations had been shown to increase
in response to exercise training. Among the factors we identified one candidate factor
which potentially mediates the anti-senescence activity. In rodent, voluntary excise
increased the blood concentration of the factor as well as the mRNA levels in skeletal
muscle. Administration of the recombinant protein significantly suppressed the cellularsenescence both in vitro and in vivo. The anti-senescence activity was further evidenced
in pulmonary emphysema models; administration of the recombinant protein suppressed
the disease-associated lung dysfunction. We further show that its serum concentration
was inversely correlated with the pulmonary function in patients with chronic
obstructive pulmonary disease, suggesting a possible involvement of this factor inhuman pathology. Collectively, these results suggest that the myocyte-derived factor
mediates the beneficial effects of exercise training through its anti-senescence activity.

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme in all living
cells and is involved in neurogenesis, inflammation, the immune system, and DNA
repair. The level of intracellular NAD+ reportedly decreases with age in tissues andorgans, including the brain. This systemic decrease in NAD+ levels during aging ispartly due to decreased nicotinamide phosphoribosyltransferase (NAMPT), the ratelimiting enzyme in the major NAD+ biosynthetic pathway in mammals. Furthermore,brain-specific NAMPT knockdown in young and aged mice reportedly reduces
hippocampal NAD+ levels and contributes to the development of cognitive impairment.
Additionally, the preventive effect of regular exercise against age-related cognitive
decline is widely known. However, no research on the relationship between
hippocampal NAD+, especially NAMPT levels, and improved cognitive function due
to exercise has been published. Here, we aimed to determine whether regular exercise
increases NAD+ levels in the hippocampus and prevents cognitive decline. Twentymonth-old female C57BL/6J mice were divided into four groups: (1) the SAL group(saline [SAL] only), (2) FK group (FK866 [FK; a NAMPT inhibitor] only), (3) SAL +Ex group (SAL + regular voluntary exercise [Ex]), and (4) FK + Ex group. All mice
were intraperitoneally injected three times a week for four weeks, specifically before
exercise in the SAL + Ex and FK + Ex groups. We revealed that regular exercise
improved working and long-term memory in aged mice. In addition, regular exercise Keywords: Myokine, Exercise, Cellular senescence.
increased NAMPT, BDNF mRNA expression, and NAD+ levels in the hippocampus inan age-related manner. Our results suggest that the prevention of cognitive decline andimprovement of cognitive function in aged mice via regular exercise are associated withincreased NAD+ levels via increased NAMPT levels in the hippocampus.
Keywords: NAD, Aging, Cognitive function,－ 69 －

P-9
P-10
Development of a fluorescent GABA sensor for drug Characterization of senescent cells derived from human
fetal fibroblasts with defective oxidative phosphorylation
discovery◯Kenji Takikawa1, Keitaro Umezawa1, Hiroshi Nishimune1, 2
1. Tokyo Metropolitan Institute of Gerontology
2. Tokyo University of Agriculture and Technology○Yasunori Fujita1, Masumi Iketani1, Masafumi Ito1, Ikuroh Ohsawa1
1. Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics andGerontology

Recent evidence suggests that abnormalities in the release and brain concentration of
GABA, a major inhibitory neurotransmitter in the brain, are involved in various
neuropsychiatric disorders and age-related disorders. Therefore, drugs that modulate therelease and brain concentration of GABA are attracting attention as therapeutic agentsfor these disorders. However, the discovery and development of such drugs have yet toprogress due to the lack of technology to measure GABA easily and quantitatively. To
address this problem, we developed a novel fluorescent GABA sensor engineered byposition-specific labeling of GABA-binding protein with a small fluorescent dye. The
sensor exhibited a moderate affinity for GABA with a 40 μM dissociation constant anda large change in fluorescence intensity with a 300% dynamic range. Furthermore, thesensor showed high selectivity for GABA, with no change in fluorescence intensity forother neurotransmitters, including glutamate at high concentration ranges of 1 mM or
higher. The sensor is expected to be applied to drug discovery by measuring GABA
release and efficacy evaluation by measuring GABA concentration in the brain.

Senescent cells are a potential therapeutic target for age-related diseases. To develop
an efficient therapeutic approach to senescent cells, the understanding of theirheterogeneity is essential. Mitochondrial function is thought to be impaired in some or
all of the cells in aged tissues. Therefore, the pre-existing mitochondrial dysfunction
before cellular senescence may contribute to the heterogeneity of senescent cells. In thisstudy, we aimed to characterize senescent cells derived from fibroblasts withmitochondrial dysfunction in vitro. We first established high-dose doxycycline-treatedhuman fetal fibroblast TIG-1 cells as a model of cells with defective oxidative
phosphorylation, which presented with swollen mitochondria and abnormal cristae
structure and showed decreased oxygen consumption rate. The long-term cultivation of
doxycycline-treated TIG-1 cells resulted in replicative senescence at higher population
doubling levels than control cells. When premature senescence was induced byetoposide, the expression level of p16 in doxycycline-treated TIG-1 cells was lower thanthat of control cells. In addition, the expression patterns and levels of senescenceassociated secretory phenotype (SASP) factors in senescent doxycycline-treated TIG-1
cells were partially different from those of control senescent cells. These results indicatethat fibroblasts with defective oxidative phosphorylation are less prone to cellularsenescence and their senescent cells have different characteristics compared to senescentcells derived from those with healthy mitochondrial function.

Keywords: GABA, Sensor, Drug

Keywords: Cellular senescence, Doxycycline, Mitochondria

P-11
P-12
Contribution of sympathetic nerve activity on skeletal Effect of a traditional Japanese herbal medicine,
Ninjin’yoeito, on static and dynamic changes in cerebral
muscle contractility in young and aged rats
corticalarteriolar diameters
11
1
1○ Harumi Hotta , Kaori Iimura , Nobuhiro Watanabe , Harue Suzuki , Masamitsu
Sugie2, Kazuhiro Shigemoto3
1. Department of Autonomic Neuroscience, Tokyo Metropolitan Institute for Geriatrics
and Gerontology
2. Health Promotion Management Office, Tokyo Metropolitan Institute for Geriatrics
and Gerontology
3. Department of Geriatric Medicine, Tokyo Metropolitan Institute for Geriatrics andGerontology○Nobuhiro Watanabe1, Kaori Iimura1, Harumi Hotta1
1. Department of Autonomic Neuroscience, Tokyo Metropolitan Institute for Geriatrics
and Gerontology

We have recently showed a feedback relationship between the muscle contraction andthe lumbar sympathetic nerve activities in rats: reflex activation of the sympathetic nerve
in response to contraction of the calf muscles facilitates contraction force of the same
muscles. We hypothesized that this feedback mechanism declines in aged rats. In thisstudy, we examined the contribution of sympathetic nerves to skeletal muscle
contractility in young adult (4-9 months old, n = 11) and aged (32-36 months old, n =11) male and female rats. The tibial motor nerves were stimulated electrically to measuretetanic force (TF) of the calf muscles. In both young and age rats, the TF amplitudedecreased by cutting the lumbar sympathetic trunk (LST), which is the rout of
sympathetic outflow to the calf muscles; however, the magnitude of the TF decrease
was smaller in the aged (6.2%) than in the young (12.9%) rats. The TF amplitude
increased during LST stimulation in both groups, but the threshold was higher in theaged (10 Hz) than in the young (5 Hz) groups. In contrast, an increase in muscle tonus
in response to LST stimulation, without motor nerve stimulation, was significantly
greater in aged compared with young rats. The sympathetic contribution to support
motor nerve-induced muscle contraction declined, whereas sympathetic-mediatedmuscle tonus, independent of motor nerve activity, was augmented in aged rats. Thesechanges in sympathetic modulation of hindlimb muscle contractility may underlie thereduction of skeletal muscle strength during voluntary contraction and rigidity of motion
during senescence.

Background: A traditional Japanese herbal medicine, Ninjin’yoeito (NYT),
reportedly mitigates cognitive decline in patients with dementia. Our earlier study
showed that intragastric administration of NYT prevents the decrease in resting cerebral
blood flow (CBF) in anesthetized mice, without affecting arterial blood pressure. In thisstudy, we investigated the effect of NYT on static and dynamic changes in the diameterof cerebral cortical arterioles.
Methods: Male C57BL/6J mice (7-9 months old) were anesthetized with urethane andartificially ventilated. Animals were intragastrically administered 1 g/kg NYT or
distilled water (DW). Blood vessels in the left parietal cortex was imaged using twophoton microscopy. Static diameter of penetrating arterioles at rest was measured before
and 50–60 min after administration. Dynamic changes in diameter, in response totransient occlusion of the left common carotid artery, were measured approximately 10
min after administration.
Results: The resting diameter of the penetrating arterioles decreased following DW
administration, but not following NYT. The diameter of the penetrating arterioles
increased during occlusion, and the increase was comparable for DW and NYT. During
reperfusion, the arteriolar diameters rapidly returned to preocclusion diameter following
DW, whereas the diameter restoration was slower following NYT. Laser-speckle
contrast imaging confirmed that CBF, although comparable during occlusion, washigher during reperfusion for NYT than DW.
Conclusion: The present results suggests that NYT attenuates vasoconstriction in
penetrating arterioles after intragastric administration and during cerebral reperfusion,
contributing to CBF regulation. NYT may contribute to the mitigation of cognitive
decline by protecting the brain from CBF perturbation.

Keywords: Sympathetic nerve, Muscle contraction, Aging

Keywords: Ninjin’yoeito, Cerebral ischemia-reperfusion, Cerebral arteriole－ 70 －

P-13
P-14
Age-related impacts of the defective programmed cell Application of senescent cell removal model mice
(tdTomato/human HBEGF knock-in mice) as a tool fordeath pathway on longevity in C. elegans
aging research○Sumino Yanase1, Rea Yamaguchi, Michiyo Suzuki2, Kayo Yasuda3, Naoaki Ishii3
1. Daito Bunka University School of Sports & Health Science
2. Takasaki Advanced Radiation Research Institute, National Institutes for Quantum
Science and Technology
3.School of Health Studies, Tokai University○Mitsuo Maruyama1,2, Tanenobu Harada1, Yuma Sugiyama1, Yoichiro Kawabe1
1. National Center for Geriatrics and Gerontology,
2. Nagoya University Graduate School of Medicine
近年、細胞老化関連遺伝子の発現制御技術の開発によって、老化細胞の可視化や除去といった制御を可能にしたモデル動物を用いた研究の進歩が著しく、個体の加齢に伴う組織機能の低下や個体の老化には老化細胞が密接に関わる
In the nematode Caenorhabditis elegans (C. elegans), the mev-1 gene encodes a large ことが明らかになってきた。我々の研究グループにおいては、Cdkn2a 遺伝子座
subunit of the enzyme succinate dehydrogenase cytochrome b, which is a component ofに 存在 する 細胞老 化マ ーカ ー分子 p16INK4a の遺 伝子 発現 に伴 い蛍光 分 子
complex II in the mitochondrial electron transport chain. Mutation of the mev-1 genecauses an increase in mitochondrial oxidative stress, thereby induces abnormal tdTomato とヒトジフテリア毒素受容体(hDTR)が発現誘導されるノックインマ
apoptosis in embryonic development and shortens the lifespan. In previous reports, a ウス(p16tdT-hDTR マウス)を作成した。in vitro での先行研究により、このマウ
mutation of ced-3 gene encoding the CED-3 caspase has recovered the lifespan in mev- ス由来の胎児線維芽細胞(MEF)が継代培養による老化で p16INK4a 遺伝子の発現
1 mutant. Here, we revealed that the susceptibility to oxidative stress in the mev-1;ced- 依存的な tdTomato と hDTR の発現ならびに、
ジフテリア毒素(DT)処理後の hDTR
3 mutant is slightly improved, at least in part. However, the recovery of the lifespan and 依存的に tdTomato 陽性細胞が選択的に除去されることを確認した。
sensitivity under hyperoxia was not observed in mev-1 mutant treated with embryonic
また、in vivo においても 9〜12 ヶ月齢の p16tdT-hDTR マウスに DT を皮下投
RNA interference (RNAi) of ced-3 gene, despite of the almost all normal developmental
与して 1 週間後以降に背部皮膚を採取し、p16INK4a および tdTomato 遺伝子の発time-courses. Furthermore, we examined the expression levels of ced-3 and ced-9 genes
on the programmed cell death cascade in the 15-day-old of mev-1 and mev-1;ced-3 現を RT-qPCR で DT 非投与個体と比較したところ、DT 投与個体では有意な発mutants, consequently detected the ced-3 gene induction dependent on CED-9/Bcl-2 現低下や皮膚組織における SA-βGal 活性の低下傾向が確認できた。これらの結suppression in mev-1 mutant. On the other hand, we had also detected the induction of 果から、p16tdT-hDTR マウスにおいては、自然加齢によって皮膚組織内に生理
sco-1 gene, which is a homologous gene of mammalian synthesis of cytochrome c 的に蓄積する老化細胞の検出および除去が可能であることが示唆された。現
oxidase (SCO2) and a target of CEP-1/p53. CEP-1/p53 is well-known the action 在、皮膚に局在する老化細胞が皮膚組織の加齢変化や老化に伴う機能低下に及upstream the programmed cell death cascade that influences C. elegans germline cell ぼす影響についての解析も進行中である。
apoptosis. These results support that an age-related novel role of programmed cell death
一方で、このマウスの加齢に伴う p16Ink4a/hDTR/tdTomato 発現上昇ならびに
through CED-3 caspase, which is regulated downstream of CEP-1/p53 and CED-9/BclDT 投与によるこれら遺伝子の発現低下は生理的な p16INK4a の発現に依存する
2, is also associated with the longevity in C. elegans during aging.
ことから、さらに皮膚組織以外に対する DT 投与/非投与個体由来組織の解析を続け、DT 処理(≒老化細胞の排除)によって発現が変化した複数の遺伝子に注目
Keywords: C. elegans, Mitochondrial dysfunction, Programmed cell death
し、 p16INK4a 依存的な老化細胞が果たす生理的機能およびメカニズムの解析の一端も紹介する。
Keywords: p16 INK4a, cellular senescence, knock-in mice

P-15
P-16
Diversity of SASP factors and their physiological roles in The relationship between ROS-induced neurite
degeneration, disruption of intracellular Ca2+
cellular senescence process
homeostasis and mitochondrial dynamics○Yoichiro Kawabe1, Yuma Sugiyama1, Tanenobu Harada1, Mitsuo Maruyama1,2◯Koji Fukui1, Kazuki Houga1, Mitsuru Wakuzawa1
1. National Center for Geriatrics and Gerontology,
1. Shibaura Institute of Technology
2. Nagoya University Graduate School of Medicine
老化は時間軸上の不可逆的な分子、細胞レベルから組織、個体レベルまでのRecently, the proportion of elderly people aged 65 and over has been increasing, and
複合的な機能低下と捉えられ、加齢性の慢性炎症をはじめとする多くの要因と it has been reported that the risk of onset of neurodegenerative diseases, such asの関連が議論されている。とりわけ細胞老化した細胞(老化細胞）や老化細胞を Alzheimer’s diseases and Parkinson’s diseases increases with age. However, there is no含む生体内の組織は加齢に伴って SASP によって炎症性サイトカインやケモカ basic treatment for these diseases. Early stages of neurodegenerative diseases involve
インを分泌し、自己や周辺細胞に対し細胞老化の誘導や慢性炎症を惹起するこ degeneration of axons and neurites, including the formation of bead-like aggregates.
Our previous studies have shown that treatment of neurons with a low concentration ofとが注目されている。 私たちは個体寿命や加齢関連疾患の罹患等、健康寿命
H2O2 induced neurite degeneration before induction of apoptosis. We attempted toの延伸を考察するための基礎老化研究として、細胞老化の多様性のメカニズム elucidate the mechanisms of neurite degeneration, which may contribute to establishingの解明は不可避と考えている。実際、進行段階の異なる老化細胞が存在し、 the prevention and treatment of these diseases. To investigate the cause of neurite
SASP の強度や分泌因子の種類において細胞老化の多様性が想定されるがその degeneration, the neurites in the H2O2-treated cells were isolated and conducted
実態はよくわかっていない。一方、私たちが新規作成したヒト CD2 抗原（hCD2） proteomic analysis. As a results, the expressions of Heat shock protein 60 and 78 kDa
をコードする遺伝子を p16INK4a が含まれる Cdkn2a 遺伝子座にノックインした glucose-regulated protein, which are mitochondria- and endoplasmic reticulum (ER) 老化細胞可視化制御マウス（以下、p16hCD2 マウス）を用いて、p16hCD2 マウ specific protein, were significantly2+ increased. Both organelles are known as calcium
stores and regulate intracellular Ca homeostasis. For these results, we investigated theス個体で免疫系の老化の進行度を可視化し、除去することで免疫老化の表現形
mechanism of neurite degeneration from the perspective of oxidative injury to cells andが緩和された事を確認できた（Y. Sugiyama et.al 2023）。
disruption of intracellular Ca2+ homeostasis. In this study, we induced neurite
そこで、今回本発表においては当該マウス由来の胚性繊維芽細胞を継代培養 degeneration by treating N1E-115 cells with a low concentration of H2O2 and ionomycin
し、p16INK4a の発現量による細胞老化の進行度ごとに細胞老化の初期段階で発 and investigated intracellular Ca2+ concentration, cellular oxidation, and localization of
現量が顕著に増加する 85 遺伝子を含むクラスター集団を抽出した。この集団 mitochondria and ER. Additionally, we confirmed accumulation of abnormally shapedには多くの SASP 因子が含まれていたことから、細胞老化の進行は付随する特 mitochondria at sites of neurite degeneration and investigated the expression of proteins
徴的な転写制御を受けることが示唆された。現在、クロマチン DNA を用いた involved in mitochondrial dynamics.
ATAC-seq で DNA の非凝集領域(転写活性化領域)を whole genome で解析し、Keywords: Neurite degeneration, Ca2+ homeostasis, Mitochondria dynamics
SASP 因子の発現制御に関わる転写制御因子が結合するゲノム領域を網羅的に解析している結果も併せて議論したい。
Related Articles:
・J Clin Biochem Nutr, 64, 36-44, 2019
・Free Radic Res, 50, 1214-1225, 2016

Keywords: SASP, p16 INK4a, cellular senescence1－ 71 －

P-17
P-18
Milk derived sialylglycopeptide concentration induce Inhibitory effect of H2-inhalation on thrombolytic tPAinduced hemorrhagic transformation of cerebral
BDNF production in SH-SY5Y neuroblastoma cells.
infarction11
1〇Hisako Nakagawa , Toshiyuki Yamaguchi and Shunjiro Kobayashi
1. Milk Science Research Institute, MEGMILK SNOW BRAND Co. Ltd.

○Kennosuke Sato1,2, Ai Tachihana1,2, Yumi Miki1,2, Masumi Iketani1, Yasunori Fujita1,
Nobuhiro Watanabe3, Harumi Hotta3, Norihiko Yamada4, Hideo Kawaguchi2, Ikuroh
Ohsawa1
1. Biological Process Aging, Tokyo Metropolitan Institute for Geriatrics andGerontology
2. Life Science, Toyo University
3. Autonomic Neuro Science, Tokyo Metropolitan Institute for Geriatrics andGerontology
4. Health Med Care, Kanagawa Pref Govt
Introduction: The only approved pharmacologic therapy for acute ischemic stroke istissue plasminogen activator (tPA). Because of the risk of intracerebral hemorrhage
associated with tPA therapy, it must be administrated within 4.5 h of stroke onset.
Inhalation of H2 gas has been reported to improve pathological conditions in manymodels of cerebrovascular disorders. We then investigated the inhibitory effect of H2inhalation on tPA-induced hemorrhagic transformation of cerebral infarction.
Methods: Middle cerebral artery in adult mice (13–15-month old) was permanently
occluded with electric scalpel. Mice were intraperitoneally injected with glucose andinhaled anesthesia with 2% H2. After 4 h, tPA (10 mg/kg) was injected via a tail vein
and intracerebral hemorrhage volume was determined further 2 h later. The rectal
temperature was continuously monitored. Coronal sections of fixed brain were stainedwith anti-vascular endothelial growth factor (VEGF) and anti-Iba1 (microglial marker)
antibodies.
Results: H2-inhalation significantly reduced hemorrhage volume and cerebral edema.
Hyperthermia induced by tPA was suppressed by H2-inhalation, but transient
hyperglycemia was not influenced. We further observed that VEGF-accumulation andmicroglial activation in the ischemic penumbra was suppressed with H2-inhalation.
Discussion: Effective inhibition of tPA-induced hemorrhagic transformation by H2inhalation may be due to anti-inflammatory effect of H2 with suppression of VEGF
expression. For practical use, we will present the effect of shorter H2-inhalation on
cerebral hemorrhage.

Dietary sialic acid may mainly regulate the growth and metabolism of gastrointestinal
microbiota and human health and development through the gut–brain axis. We have
prepared milk-derived sialylglycopeptide (mSGP) concentrate containing sialylated Oglycans from an ingredient derived from cheese whey, and have demonstrated its
efficiency, such as growth-promoting effects on certain species of bifidobacteria andimproving memory of C.elegans. In this study, we investigated that the effects of mSGP
on the Brain derived neurotrophic factor (BDNF) production and differentiation of SHSY5Y cells.
The mSGP concentrate treatment caused a significant increase in the BDNF protein
levels in SH-SY5Y cells compared to control. As a result of verifying the active
ingredients, mSGP concentrate treated with neuraminidase and O-glycosidase did notaffect BDNF protein level. The effects of sialylglycopeptide purified from mSGP
concentrate was equivalent to that of mSGP concentrate. The sustained treatment with
Retinoic acid (RA) and BDNF has been reported to enhance neuronal differentiation of
SH-SY5Y cells. We evaluated that the effects of mSGP concentrate on differentiationlevels using morphological changing, neurite length, and immunofluorescence detectionof microtubule-associated protein 2 (MAP2). Treatment with RA and mSGP concentrateinduced branching of longer neurites and detectable network formation than in RA
treated cells.
In conclusion, our experiments indicated that sialic acid-containing glycan moiety ofmSGP regulated SH-SY5Y differentiation through BDNF production.
Keywords: Sialylglycopeptide, BDNF

Keywords: Hydrogen gas, Microglia, VEGF

P-19
P-20
Induction of tissue-specific premature stem cell aging Effect ofof basal
basal forebrain
forebrain stimulation
stimulation ononextracellular
extracellularregional
blood
flow inthe piriform
releaseandandregional
blood
flow
in thepromotes senescence-like deterioration in remote organs acetylcholine releasecortexpiriform
cortex111
1
1○Hayato Kaneda , Yasuaki Ikuno , Yukie Kande , Dai Ihara , Yu Katsuyama
1. Shiga University of Medical Science〇Jura Moriya1,2, Daichi Morihara1,2, Fusako Kagitani1, Sae Uchida1
1. Department ofof Autonomic
AutonomicNeuroscience,
Neuroscience,Tokyo
TokyoMetropolitan
MetropolitanInstitute
Institutefor
forGeriatrics
Geriatricsand
andGerontology
Gerontology
2. Tokyo University of Agriculture and Technology

Age-related dysfunction of tissue stem cells (SCs) has emerged as a factor
contributing to the disruption of tissue homeostasis. However, the common molecularbasis of senescence in various SCs and its contributions to organismal aging remain
largely unexplored. Here we show that dysregulation of the DNA damage response
Olfactory dysfunction isis one
disease(AD).
oneofofthe
theearliest
earliestsymptoms
symptomsofofAlzheimer’s
Alzheimer’s
disease(AD)(DDR), modulated by lymphoid enhancer-binding factor 1 (Lef1) and DDR-microRNAs Cholinergic neurons
patients
withneurons inin thethebasal
basalforebrain
forebrainundergo
undergosevere
severedegeneration
degenerationin inpatients
with(DDR-miRs), is the common molecular basis for SC aging. We identified Lef1 as the AD. The piriform
axonalpiriform cortex,
cortex, aamajor
majorolfactory
olfactorycortical
corticalarea,
area,receives
receivescholinergic
cholinergic
axona
most repressed transcription factor with aging in common between mesenchymal projections from neurons
limb
ofof
thethediagonal
neurons originating
originatingininthe
thenucleus
nucleusofofthe
thehorizontal
horizontal
limb
diagonastem/stromal cells (MSCs) and hematopoietic stem/progenitor cells. Similar to the band of Broca
whetherthetheBroca (HDB)(HDB) inin thethebasal
basalforebrain.
forebrain.This
Thisstudy
studyaimed
aimedtotoclarify
clarifywhether
expression profiles of aged MSCs, Lef1 knockdown reduced the expression of a broad extracellular acetylcholine
acetylcholine (ACh)(ACh)release
releaseandandthetheregional
blood
flow
in piriformthe piriform
regional
blood
flow
in thecortexrange of miRNAs, including DDR-miRs, in young MSCs. DDR capacity was also cortex
is influenced
by stimulationof theforebrain.
basal forebrain.
is influenced
by stimulationof the basal
diminished in aged SCs in vivo. Moreover, Lef1 deficiency in intestinal or epidermal
Using urethane-anesthetizedurethane-anesthetizedrats,
rats,extracellular
extracellularACh
ACh
concentrationin piriformthe piriform
concentrationin thecortexSCs induced precocious dysregulation of DDR, inflammation, and senescence in the cortex
was measured
microdialysis
performanceliquidchromatographyand
was measured
using using
microdialysis
with withhighhigh
performanceliquidchromatography
remote organs. This study demonstrates that the Lef1/DDR-miR axis is the common andelectrochemical
detection(HPLC–ECD).
Regionalblood
blood flow
flow inelectrochemical
detection(HPLC–ECD).
Regional
in thethepiriform
piriformwas
wasmolecular basis underlying SC aging and that its regulation enables us to investigate the measured by aa laser
stimulated
laser Doppler
Dopplerflowmeter.
flowmeter.The
Theunilateral
unilateralHDB
HDBwaswasfocally
focally
stimulated
inter-organ influences of specific SC aging.
chemically by
L- Lby microinjection
microinjection ofofL-glutamate.
L-glutamate.Following
Followingthe
theHDBHDBstimulation
stimulationwith
withglutamate (50 nmol),wasnmol), thethe extracellular
extracellularACh
AChlevellevelininthe
theipsilateral
ipsilateralpiriform
piriformcortex
cortexwas
Keywords: Stem cell aging, DNA damage response, MicroRNA
increased by 36%.
increased
36%. Microinjections
Microinjections ofofL-glutamate
L-glutamate(50(50nmol
nmolandand100100nmol)
nmol)
increasedregional blood
blood flow
flowininthe
thepiriform
piriform
cortex12%27%,
respectively.
The meancortexby by
12%andand27%,
respectively.
The meanarteriaarterial
not affectedsignificantly
by thestimulation.
HDB stimulation.
pressurepressure
was notwas
affectedsignificantly
by the HDBThis study showed
showed thatthat stimulation
stimulation ofof thetheHDB
HDBininthethebasal
basalforebrain
forebrainincreases
increases
extracellular ACh release
The
increased
release andandregional
regionalblood
bloodflow
flowininthe
thepiriform
piriformcortex.
cortex.
The
increased
blood flow may
olfactory
may contributecontribute totothe
theprotection
protectionofofneurons
neuronsand
andmaintenancemaintenanceof ofolfactory
function.
Keywords: Piriform cortex, Acetylcholine release, Regional blood flow2

－ 72 －

P-21
P-22
Analysis of Selective mRNA Splicing in Adipose tissue MMP-2 regulation improves age-related skin pathologies
following Caloric Restriction
caused by oxidative stress○Yuhei Mizunoe1, Mitsuki Kumagai1, Yuka Nozaki1, Masaki Kobayashi2,3, Yoshikazu
Higami1,4.
1. Laboratory of Molecular Pathology and Metabolic Disease, Faculty of
Pharmaceutical Science, Tokyo University of Science
2. Department of Nutrition and Food Science, Graduate School of Humanities andSciences, Ochanomizu University
3. Institute for Human Life Innovation, Ochanomizu University
4. Division of Cell Fate Regulation, Research Institute for Biomedical Science, Tokyo
University of Science○Shuichi Shibuya1, Kenji Watanabe1, Takahiko Shimizu1
1. Aging Stress Response Research Project Team, National Center for Geriatrics andGerontology

Age-related disruption of extracellular matrix (ECM) homeostasis in skin causes
abnormalities of skin function. Previously, we revealed that the skin of mice lacking theantioxidant enzyme SOD1 (Sod1-/-) exhibits age-related skin atrophy and increased
expression of matrix metalloproteinase 2 (MMP-2), a member of the ECM degrading
enzyme family. These results suggest that excessive MMP-2 in Sod1-/- skin causes agerelated skin atrophy via increase of ECM degradation. In this study, we investigated theCaloric restriction (CR) reduces the pathological changes associated with aging and effect of excessive MMP-2 regulation on aging-like skin pathologies caused byextends average and healthy life span. Selective mRNA splicing is a mechanism to oxidative stress in Sod1-/- mice. First, we generated Sod1, Mmp2 double-deficient mice
generate more diverse proteins from limited genetic information, and in C. elegans, and analyzed their skin pathologies. Since the Sod1-/-, Mmp2-/- mice were small in bodytreatment with resveratrol, an activator known to mimic CR, has been reported to affect size and growth retarded, we analyzed Sod1-/-, Mmp2+/- mice. Sod1-/-, Mmp2+/- miceselective splicing. In mammals, however, there are few reports that have analyzed at the exhibited significant increase of skin thickness compared to Sod1-/-, Mmp2+/+ mice,molecular level how selective splicing changes affect the anti-aging and lifespan- indicating attenuation of skin atrophy. Sod1-/- Mmp2+/- mice showed upregulation ofextending effects of CR. In this study, we focused on selective splicing changes in Co11a1 gene expression and downregulation of Tnf-a gene expression in skin.
subcutaneous white adipose tissue (sWAT) and aimed to elucidate some of the Furthermore, Sod1-/- Mmp2+/- mice exhibit marked increase of COL17 in basal layer,
molecular mechanisms of CR through comprehensive gene expression analysis.
suggesting improvement in skin atrophy through restoring of the basal layer
Pathway analysis using count data from RNA-seq data in sWAT of CR mice revealed homeostasis. Next, to examine the effects of pharmacological MMP-2 inhibition, wethat factors involved in lipid metabolism were increased. To test the possibility that these administered the MMP inhibitor batimastat transdermally to the skin of Sod1-/- mice.
factors causing changes in lipid metabolism undergo selective mRNA splicing, we Batimastat significantly improved skin atrophy in Sod1-/- mice. Furthermore, we treatedperformed analysis using rMATS. We found that exon13 of Ncoa2 was decreased by batimastat transdermally to surgically created wound sites on the skin of Sod1-/- miceexon skipping. NCOA2 protein is an important coactivator of PPARγ, which is involved and investigated its effect on wound healing. Wound healing in Sod1-/- mice wasin lipid metabolism and adipocyte differentiation, in WAT. Therefore, we analyzed the significantly delayed compared to Sod1+/+ mice, whereas treatment of batimastat
coactivator function of full-NCOA2 with exon 13 and delta-NCOA2 without exon 13 significantly accelerated its wound healing. Retain of ECM homeostasis in the skinthrough the promoter activity of PPARγ. The results showed that the transcriptional through MMP-2 regulation is expected to be applied as a strategy to improve age-related
activity of PPARγ was increased in full-NCOA2 compared to delta-NCOA2.
skin pathologies.
These results suggest a novel mechanistic pathway of CR in which CR-induced
splicing factor alteration leads to an increase in full-length NCOA2 due to altered Keywords: Skin atrophy, Matrix metalloproteinase, Oxidative stressselective splicing of NCOA2 in WAT, which enhances metabolic activity through its
coactivator function.
Keywords: Caloric restriction, Selective mRNA splicing, NCOA2

P-23
Study of skeletal muscle aging using human iPS cells

P-24
Assessment of physical and cognitive decline in aging
mouse model◯Makoto Shimizu1,2, Hiroki Sato2, Hidetoshi Sakurai3, Masamichi Kamihira4, Kazuaki
Takafuji5, Junichiro Takaya5, Yoshio Yamauchi2, and Ryuichiro Sato2
1. Graduate School of Humanities and Sciences, Ochanomizu University
2. Graduate School of Agricultural Sciences, The University of Tokyo
3. Center for iPS Cell Research and Application, Kyoto University
4. Graduate School of Engineering, Kyushu University
5. Suntory Global Innovation Center Limited○Shuichi Yanai1, Tomoko Arasaki1, Shogo Endo1
1. Tokyo Metropolitan Institute for Geriatrics and Gerontology

骨格筋は人体最大の運動器であり、身体機能の維持に重要な組織である。超高齢社会である我が国において、要支援・要介護人口の増加による医療介護費の膨大化は深刻な問題である。加齢に伴う筋量や筋力の低下など骨格筋の老化
により身体活動レベルが低下する。このことから、骨格筋の老化機構を解明し骨格筋を中心とした抗老化機構を提案することは健康長寿社会実現のため重要な課題である。これまでの骨格筋老化研究は、サテライト細胞や間葉系前駆脂肪細胞など増殖性の細胞に着目したものが多く、骨格筋の大部分を占める非増殖性筋細胞から構成される筋線維の老化機構は未解明である。本研究では、
ヒト iPS 細胞由来骨格筋細胞を使用し、ヒト骨格筋線維の老化機構の解明を試みた。放射線照射を用いた老化模倣刺激をヒト iPS 細胞由来骨格筋細胞に与えた結果、老化マーカーの発現亢進や筋繊維の萎縮が確認された。電気パルス刺激を用いた解析の結果、老化模倣刺激による筋収縮力能の低下が確認された。
老化細胞は炎症性サイトカインなど老化に関わる様々なタンパク質を分泌することが報告されている。iPS 細胞由来骨格筋細胞の RNA を用いた RNA シー
ケンスや、培養上清を用いたプロテオミクス解析の結果、複数の炎症性サイト
カインが増加していることを見出した。炎症性サイトカインの下流シグナルを
p38 MAP
解析した結果、老化模倣刺激により p38 MAP kinase が活性化すること、
kinase の阻害により、老化模倣刺激による炎症性サイトカイン誘導の抑制、及び筋収縮力能の改善が認められた。以上の結果から、p38 MAP kinase シグナルが骨格筋老化の重要な制御因子である可能性が示唆された。

マウスでは 10～12 ヶ月齢頃にヒトの中年に相当する段階が始まり、18～20 ヶ
月齢頃にヒトの老年に相当する段階が始まると考えられている。身体を支える
筋肉や運動の機能、高次脳機能の基盤である記憶など、老化は様々な心身機能の低下を伴うが、ある機能について介入を行う際は、老化に伴う当該機能の変化を検討し、それが変化し始める前に実験を開始するよう計画する。このように、介入の効果を検討するためには実験を開始するタイミングが非常に重要であるにも関わらず、若齢マウスの健常な心身機能が障害を呈するまでのプロセスに関する知見は少ない。心身機能の老化に関する基礎データが十分ではない
現状を鑑み、我々は老化モデルマウスとして広く用いられる C57BL/6J オスマ
ウスに対して 3、6、12、18、22 ヶ月齢で網羅的行動解析を行った。認知機能として空間記憶の解析を、認知機能の測定結果に影響を与えうる身体機能として
自発活動量、走行速度、握力の解析を行い、加齢依存的変化の観点から心身機能の老化関連表現型を評価した。
その結果、加齢に伴う各種表現型の変化は非線形であること、また加齢の様
態は表現型特異的であることが明らかになった。握力は全評価項目中最も早く、3 ヶ月齢と比較して 6 ヶ月齢で機能低下が認められた。次いで走行速度が12 ヶ月齢、自発活動量が 18 ヶ月齢で機能の低下が認められた。認知機能は要求される注意水準の多寡によって低下速度が異なり、多くの注意が必要な指標
では 22 ヶ月齢で顕著な障害が認められた。一方、多くの注意が求められない
指標は年齢依存的に機能が低下するものの、その程度は緩慢であった。身体機
能は認知機能よりも早く衰えること、また年を取っても保たれる記憶があることなど、マウスの老化にはヒトの老化と共通した特徴があることが明らかになった。

Keywords: 骨格筋、老化、ヒト iPS 細胞

Keywords: 網羅的行動解析、認知機能、身体機能3－ 73 －

P-25
P-26
Age-associated changes in the amount of nucleotide Age-related changes in the N-glycan expression of mousesugars in mouse tissues
lung○Rieko Imae1, Hiroshi Manya1, Hiroki Tsumoto2, Yuri Miura2, Tamao Endo1
1. Molecular Glycobiology, Tokyo Metropolitan Institute of Gerontology
2. Proteome Research., Tokyo Metropolitan Institute of Gerontology○Keiko Akasaka-Manya1, Hiroshi Manya1, Hisatoshi Hanamatsu2, Nobuaki Miura2,
Jun-ichi Furukawa2, Tamao Endo1
1. Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo
Metropolitan Institute of Gerontology
2. Division of Glycobiology -Systems Biology, Institute for Glycobiology -core
Research (iGCORE), Nagoya University

Glycosylation is the ubiquitously observed modification of proteins and lipids, andregulates many physiological and pathological processes. Aging affects tissue glycan
profiles, which may alter cellular functions and increase the risk of age-related diseases.
Approximately 10 nucleotide sugars are used as the sugar donors in the glycan
biosynthesis, and the availability of nucleotide sugars affects glycosylation efficiency.
However, the effects of aging on nucleotide sugar profiles and contents are yet to beelucidated. In this study, we developed a new LC-MS/MS method to comprehensively
quantify the major nucleotide sugars in mammals and determined the nucleotide sugar
contents of various tissues (brain, liver, heart, skeletal muscle, kidney, lung, and colon)of male C57BL/6NCr mice (7- or 26-month-old). Characteristic age-associatednucleotide sugar changes were observed in each tissue sample. Particularly, there was asignificant decrease in UDP-glucuronic acid content in the kidney of aged mice and adecrease in the contents of several nucleotide sugars, including UDP-glucose and UDPN-acetylglucosamine, in the brain of aged mice. Additionally, regardless of the age,
there were variations in nucleotide sugar profiles among the tissues. For example, thekidneys had the highest concentration of UDP-glucuronic acid among the seven tissues.
These findings may contribute to the understanding of the roles of glycans in tissue
aging.

The glycans attached to proteins undergo structural and quantitative changes withaging. The relationship between these alterations in glycosylation with tissue
dysfunction and disease has been revealed recently. Investigating the mechanism andeffects of glycosylation is important for understanding the causal relationship between
glycan and aging or aging-related diseases, and the physiological significance ofglycans. In this study, a comprehensive tissue glycome analysis was conducted using
mouse models of chronological aging and aging-related diseases. The expression
profiles of total N-linked glycans were analyzed in the lungs of α-Klotho mice, a modelof aging-related diseases, and in the serum and organs (liver, lung, heart, andgastrocnemius muscle) of chronologically aged mice from 6 to 30 months. N-linked
glycans were purified and labeled from each organ using GlycoBlotting and aminolysisSALSA methods, then subjected to sialic acid binding mode-specific modifications andanalyzed comprehensively and quantitatively by mass spectrometry (MALDI-TOFMS). Some comparable alterations of N-linked glycans were observed among different
organs while some glycans exhibited tissue-specific alterations. Furthermore,
paucimannose-type glycans were found to increase in serum, lung, and gastrocnemius
muscle with aging.
In addition, RNAseq was utilized to analyze the expression of glycan-related
molecules in the lungs, which revealed age-related changes in the glycan biosynthesis
pathway.

Keywords: Nucleotide sugar, Mouse tissue, Aging

Keywords: Glycan, Glycome analysis

P-27
P-28
Change of fucosylated N-glycans in plasma proteins from A transcriptomic atlas of the adult mouse skeletal muscle
and satellite cells: toward understanding age-relatedsemi-supercentenarians
sarcopenia
12
3
4○Hiroki Tsumoto , Takashi Nishikaze , Yasumichi Arai , Kazunori Ikebe , Tatsuro
Ishizaki1, Kei Kamide4, Yasuyuki Gondo4, Yukie Masui1, Nobuyoshi Hirose3,
Yoshihiro Hayakawa2, Yuri Miura1, Tamao Endo1
1. Tokyo Metropolitan Institute for Geriatrics and Gerontology
2. Shimadzu Corporation
3. Keio University
4. Osaka University○Yuuki Gouda1, Ryosuke Okino1, Yusuke Ono1,2
1. Muscle Biology Laboratory, Tokyo Metropolitan Institute for Geriatrics andGerontology
2. Department of Muscle Development and Regeneration, Institute of Molecular
Embryology and Genetics, Kumamoto University
加齢性筋脆弱症(サルコペニア)は全身の骨格筋が一様に萎縮するわけではな
く，あまり影響を受けない部位が存在する。このような身体部位特異的な骨格筋の加齢変容の分子細胞基盤は明らかになっていない。サテライト細胞は、骨格筋の肥大や再生を司る筋幹細胞であり、サルコペニアに対する再生治療応用が期待されている。一方、加齢によりサテライト細胞の数や機能は低下することが知られている。本研究は、サルコペニア発症の分子基盤を理解することを目的とし、マウス遺伝子発現アトラスを作成した。8～12 週齢のマウスの頭部、体幹、前肢、後肢の 4 部位から、咬筋、僧帽筋、上腕二頭筋、長指伸筋など代表的な 23 種類の骨格筋をおよびそれに付随するサテライト細胞を用いて RNA
シークエンス解析を行い、遺伝子発現アトラスを作成した。まず、全遺伝子中の発現量が高い上位 1,000 遺伝子を用いて主成分分析を行った。しかし、骨格筋およびサテライト細細胞ともに、頭部、体幹、前肢、後肢の部位間に明確な分離は見られなかった。続いて、頭部、体幹、前肢、後肢の各部位を特徴付ける遺伝子セットを決定するために、他の３部位と比較し部位毎に有意に発現が高い遺伝子を抽出した。さらに、同様の方法で部位内の個々の筋を特徴付ける
遺伝子セットを抽出した。一連の解析により、重複を除いた 35 遺伝子を、23種類の骨格筋を分類できる遺伝子セットとして同定した。以上の結果から、全身の各骨格筋およびサテライト細胞をクラスタリングできる遺伝子を新たに同定することができた。今後、アトラスを活用し、骨格筋の加齢変容の部位特異性を解明する。

Aging is a complex process which is regulated by various genetic and environmental
factors. The underlying insights into molecular mechanisms of aging might allow us toincrease healthy life expectancy. Semi-supercentenarians (SSCs, � aged 105) areconsidered to be a good model of human longevity. Therefore, physiological andbiochemical analyses of SSCs can contribute to the understanding of healthy humanaging. Glycosylation of plasma proteins is one of the most common post-translational
modifications and a suitable analysis target because glycosylation changes depending
on biological environment such as disease and aging.
In this study, we performed N-glycomics of human plasma proteins using sialic acidlinkage-specific alkyl amidation and mass spectrometry for the identification of Nglycans which is characteristic of SSCs. We used samples of aged 70, 80, and 90 fromthe 3-year SONIC (Septuagenarians, Octogenarians, Nonagenarians Investigation withCentenarians) longitudinal cohort study of older Japanese people, and of SSCs from theJapan Semi-supercentenarian Study. N-Glycan profiles of SSCs obtained by MALDIMS were compared to that of aged 70, 80, and 90. As a result of multivariate analysis,
it was suggested that N-glycans containing fucose (Fuc) were up-regulated in SSCs.
However, position of fucose, antennae or core, remains unknown. Therefore, further
study was performed using LC-ESI-MS(/MS). Among 13 mono-fucosylated N-glycans
which were identified as characteristic of SSCs by MALDI-MS, 8 N-glycans were a
mixture of antennary- and core-Fuc and 5 N-glycans were only antennary- or core-Fuc.
In the case of the mixture, only antennary-Fuc significantly increased in SSCs whencompared to aged 70, 80, and 90.
We found an increase of antennary-fucosylated N-glycans in SSCs which may be thekey for longevity and healthy aging.

Keywords: 部位特異性、骨格筋、サルコペニア

Keywords: Semi-supercentenarians, N-glycomics, Fucosylation

4－ 74 －

P-29
Approaches for Identifying of Active Substances in
Hypochlorous Acid-Based Disinfectants: Application of
Absorption Spectrophotometry and IodometryP-30
The comparison of dissolved components, effective
chlorine concentration and free chlorine concentration
between electrolyzed and non-electrolyzed hypochlorousacid water○Yuta Okada1, Ayuta Kishimoto2, Kenta Sugiyama1, Masahiro Kohno1, Koji Fukui1,2
1. Graduate School of System Engineering and Science, Shibaura Institute ofTechnology
2. Graduate School of Functional Control Systems, Shibaura Institute of Technology○Kenta Sugiyama1, Ayuta Kishimoto2, Yuta Okada1, Kohno Masahiro1, Koji Fukui1,2
1. Graduate School of System Engineering and Science, Shibaura Institute ofTechnology
2. Graduate School of Functional Control Systems, Shibaura Institute of Technology

次亜塩素酸ナトリウム(NaOCl)を主成分とする殺菌剤は従来，優れた酸化力を活かして殺菌に用いられてきた。しかし、その殺菌メカニズムや殺菌活性物
質には未だ不明な点が多く、高精度な殺菌評価法も確立されていない。現在利用されている殺菌評価法の一つとして，水道法に準じたヨウ素還元滴定法(KI法)がある．これは試料溶液中に存在する酸化性物質の総量を測定する基本的な方法だが，測定される物質の実態は不明である．そこで本研究では、次亜塩素
酸ナトリウム由来の物質に対して様々な条件で吸光光度法と KI 法を実施し、KI 法で測定される酸化性物質の同定にアプローチした。
試料溶液として、NaOCl 溶液と、2 種の異なる酸を用いて酸性化した NaOCl
溶液を調製した。これらの溶液に吸光光度法と KI 法を実施した結果、酸化性物質の総量が溶液の有する殺菌力の強さと一致しなかった。また、酸性化
NaOCl 溶液は用いた酸の違いによって同じ pH でも異なるピークを示し、酸化性物質の総量も異なった。さらに，試料溶液がもつ本来の酸化力を測定できる条件に変更して KI 法を実施した結果，NaOCl 溶液は主成分のピークと酸化性物質の総量が一致しなかった。
実験結果より、KI 法では 2 種の酸性化 NaOCl 溶液で異なる酸化性物質が測定されていることが示唆された。また、NaOCl 溶液の主成分として知られている物質は酸化力をもたず、他の物質が殺菌に関与している可能性がある。したがって。KI 法は次亜塩素酸類が本来有する殺菌力を適切に測定できないだけでなく、測定される物質が一般に考えられている酸化性物質とは異なると考えられる。

新型コロナウイルスによるパンデミックの影響により、世間の消毒・殺菌に対する関心が高まっている。その中で、近年では次亜塩素酸水による消毒・殺菌が注目されている。次亜塩素酸水はアルコールが効かない芽胞菌やノンエン
ベロープウイルスに有効であることが確認されているうえ、皮膚や口・鼻の粘膜に付着しても炎症を引き起こさない安全性が確認されている。そのため医療、食品、農業、家庭などの幅広い分野で用いられる。次亜塩素酸は溶液の pHの影響を受けて構造が変化する性質が報告されているため、一般的に次亜塩素
酸水は弱酸性で使用されている。しかし、次亜塩素酸水の製造や販売において規格や基準が定められていないため、製造元によって品質にばらつきが生じ、消費者の混乱を招いている。この背景には次亜塩素酸水の製造方法が電解型と非電解型に大きく分類され原料と製法が統一されていない実情がある。さらに次亜塩素酸水の詳細な殺菌活性種や殺菌機構も解明されていない。
そこで我々は電気分解装置を用いて塩化ナトリウム溶液を電気分解した電解型の次亜塩素酸水と次亜塩素酸ナトリウム溶液に塩酸を添加した非電解型の次亜塩素酸水を作製し、電解型と非電解型の次亜塩素酸水中に含まれる溶存成分を吸光光度計を用いて調査し比較した。さらに塩素系殺菌剤の殺菌効果を示す指標である有効・遊離塩素濃度を電解型と非電解型の次亜塩素酸水で測定し、その相違を手掛かりに殺菌活性種と殺菌機構の解明に向けてアプローチした。
その結果、電解型と非電解型の次亜塩素酸水はアルカリ性、弱酸性、強酸性で特有のピークが出現した。電解型と非電解型は液性ごとに同様のピークを示したが、有効・遊離塩素濃度は大きく異なる値を示した。このことから電解型と非電解型は溶存する物質や殺菌作用が異なると考えられる。今後、次亜塩素酸水に含まれる物質やその構造について更なる検討が必要である。

Keywords: 次亜塩素酸類，吸光光度法，ヨウ素還元滴定法

Keywords: 次亜塩素酸水、有効塩素濃度、遊離塩素濃度

P-31
Analysis of sodium chlorite and acidified sodium chloriteby various measurement methods○Ayuta Kishimoto1, Ryosuke Ohtsubo2, Yuta Okada3, Kenta Sugiyama3, Hisataka
Goda4, Toshikazu Yoshikawa5.6, Masahiro Kohno1.2.3.5, Koji Fukui1.2.3
1. Graduate School of Functional Control Systems, Shibaura Institute of Technology
2. Department of System Engineering and Science, Shibaura Institute of Technology
3. Graduate School of System Engineering and Science, Shibaura Institute ofTechnology
4. Sankei Co. Ltd.
5. Louis Pasteur Center for Medical Research
6. Kyoto Prefectural University of Medicine
The chlorin-based disinfectants are attracting attention as an alternative to alcohol.
The main ingredients are chlorine compounds such as sodium hypochlorite,
hypochlorous acid and chlorous acid. In Japan, sodium hypochlorite is often used forsterilization. The reason is that it could sterilize spore-forming bacteria that cannot besterilized with alcohol treatment. However, due to the strong sterilizing power, there
were problems such as safety to the human body and a decrease in sterilizing power
when it reacts with organic matter. Therefore, it is important to discover new
disinfectants that are as effective as sodium hypochlorite and safer. Acidified Sodium
Chlorite (ASC) is one of the most promising disinfectant candidates to replace sodium
hypochlorite. It is made acidic by adding hydrochloric acid or citric acid to sodium
chlorite. ASC has been approved by the Food and Drug Administration (FDA) for use
as an indirect food additive. Although its oxidizing power is weak, it also has the power
to sterilize spore-forming bacteria. Thus, ASC is considered safe for humans. However,
the mechanism and main components that kill bacteria were not clear. Therefore, it isnecessary to identify the composition of ASC and clarify its the mechanism andsubstances with bactericidal activity.
This study aims to clarify the composition of sodium chlorite and ASC using aspectrophotometer, pH meter, ion chromatography, Electron Spin Resonance and DPD
method. As a result, it was found that sodium chlorite contains trace amount of sodium
hypochlorite. The main compounds of ASC for sterilizing bacteria are radical. In thispresentation, we would like to introduce the detailed results.
Keywords: Ion chromatography, Electron spin resonance, Acidified sodium chlorite

5－ 75 －

〈 企業シンポジウム 〉
６月 15 日（土） 13：30～14：30
The effectiveness of Lactic Acid Bacteria for“Health Aging”
Hisako Nakagawa
MEGMILK SNOW BRAND Co., Ltd
Electron Spin Resonance（ESR），
Instrument for detecting radicals
Yumi Nakai
JEOL Ltd
Rare sugar ～ Potential for healthy aging ～Akane Kanasaki
Matsutani Chemical Industry Co., Ltd
座長：中川
柳井

久子（雪印メグミルク株式会社）
修一（東京都健康長寿医療センター研究所）

The effectiveness of Lactic Acid Bacteria for“Health Aging”
Hisako Nakagawa
Milk science Research Institute, MEGMILK SNOW BRAND Co., Ltd.

The potential benefits of Lactic acid bacteria（LAB）for human and animal health include
stimulation of the immune system, balance of intestinal flora, lowering of serum cholesterol,and nutraceutical effects. Lactobacillus helveticus SBT2171（LH2171），a common starter
bacterial strain in Gouda-type cheese production, attenuated Experimental Autoimmune
Encephalomyelitis in Mice by reducing the expression level and production of Th17-inducing
cytokines such as IL-6［1］．Furthermore, LH2171 significantly improved nasal symptoms via
suppression of eosinophils in individuals experiencing symptoms of ocular and nasal discomfort
by house dust, mite, or pollen［2］．

Lactobacillus paragasseri SBT2055（LG2055）has been shown to have beneficial effects inmice and humans, including improving the intestinal environment, preventing influenza A
virus infection, increasing IgA production, and having anti-obesity effects. We also showedthat feeding with LG2055 effectively extended the life span of C . elegans by increasing stressresistance and stimulating the immune response［3］．Furthermore, it was suggested that
LG2055 activated the Nrf2-ARE signaling pathway, and it strengthened the anti-oxidative
defense system against mitochondrial damage in mammalian cells. For other LAB that have abeneficial effect on age-related functional decline, we conduct behavioral tests on C . elegans andD.melanogaster in order to screen. In this session, our initiatives on the effectiveness of LAB for“Health Aging” will be introduced.
［1］．Front Microbiol, 2017. 8：p.2596.
［2］．Nutrients, 2020. 12（12）．
［3］．Aging Cell, 2016. 15（2）：p.227-36.

－ 78 －Electron Spin Resonance（ESR），Instrument for detecting radicals
Yumi Nakai
NM Application Department（ESR），JEOL Ltd.

ESR is the only instrument that can detect radicals produced in a sample. It is characterized
by its extremely high selectivity, requiring almost no sample pretreatment.
Among the reactive oxygen species（ROS）involved in biological reactions, superoxide（O2・-）and hydroxyl radical（HO・）are considered radicals. Singlet oxygen（1O2）is not a radical, but it
has attracted attention due to its high reactivity. Despite their extremely short lifetimes, these
species can be measured using spin-trapping agents and other detection reagents. ESR allows
for the discrimination and quantification of these ROS. While these radicals play a positive roleas part of the body’s defenses, they are also believed to contribute to the degradation of lipid
membranes and proteins, thereby triggering diseases and aging. ESR has been extensively
utilized in studies, primarily focusing on examining ROS generation and scavenging in vitro.
The most researched area utilizing ESR is the ROS scavenging activity of biological,
pharmaceutical, dietary, and other substances. Although various methods exist for evaluating
antioxidant activity, ESR stands out by independently evaluating the scavenging activity of
three types of ROS generated in the body. Therefore, it is possible to characterize a sample
based on its reactivity with these three types of ROS.
In my lecture, I will present several examples of studies using ESR to investigate ROS
scavenging, as described above, and explore the potential formation of ROS in vivo.
・中井

由実 他、薬物動態（1988）3（5），674・Hashimoto, M., et al.（1997）Chem. Lett . 71
・Kumagai, Y., et al.（1997）Free Rad. Biol . Med . 22, 479
・Abiko, Y., et al.（2019）Chem. Res. Toxicol . 32
（4）551－ 79 －

Rare sugar ～ Potential for healthy aging ～Akane Kanasaki
Matsutani Chemical Industry Co., Ltd

Rare sugar is a general term for monosaccharides that exist in less amount in nature, of which
there are more than 50 types. Because of the small amount of rare sugars, research on theirhealth functions has been slow. However, the discovery of rare sugars production enzymes has
made it possible to mass produce them, and health function research of them has accelerated
in recent decades. One of the rare sugars, D-allulose, is a C-3 epimer of D-fructose, and its use
in foods and beverages is expanding worldwide as a 0-kcal sweetener. D-Allulose has several
health functions, and it is used as a functional ingredient in the Foods with Functional Claim
System in Japan. Another rare sugar, D-allose, is a C-3 epimer of D-glucose, is still in the
research phase, and is being studied for its health functions, including those related to aging. In
this symposium, we introduce the potential of some rare sugars for healthy aging.

－ 80 －

〈スポンサードセミナー〉
６月 15 日（土）11：30～12：15
老化治療の最前線
講師：犬房

春彦（岐阜大学科学研究基盤センター 共同研究講座
抗酸化研究部門

特任教授）

TIMA Tokyo 株式会社座長：福井浩二（芝浦工業大学）

６月 16 日（日）12：30～13：15
産学連携による室戸海洋深層水の利用促進に向けた取組み
講師：福井

浩二

（芝浦工業大学 システム理工学部 生命科学科
分子細胞生物学研究室 教授）
株式会社タケナカ
座長：加藤優吾（鳥取大学）

老化治療の最前線
犬房春彦

岐阜大学 科学研究基盤センター 共同研究講座 抗酸化研究部門 特任教授
近年、老化治療という言葉が使われている。治療と称するからには老化を疾患と捉えているのであろう。
老化治療のコンセプトも方法も多種多様であるが、ほとんどが治療ターゲットを一つに絞り込んだものである。老化や高齢が最大危険因子であるアルツハイマー病（AD）の予防治療薬もその一つである。世界中の製薬会社はこれまでに、脳に蓄積するアミロイドβ（Aβ）をターゲットとした薬の開発に 60 兆円
以上もの大金を投じてきたが、現在に至っても成功していない。なぜなら AD の主要因が Aβであるとの虚偽とされるデータが記載された論文を盲信し、単一のターゲットにのみ焦点を当てて研究がなされたからであろう。脳に蓄積されるゴミは Aβだけでなくタウ蛋白質をはじめ数十種類あり、酸化ストレスや炎症の持続した増加、ミトコンドリア機能やオートファジー機能低下、新生細胞数やテロメアの減少なども一因である Aβを減らすだけでは認知症状は改善しないのは当然である。老化治療の候補として
NMN や老化細胞除去のワクチンが挙げられているが、いずれも臨床試験で有意な効果を示しているとは言い難い。それは単一の成分や化学物質にのみ焦点を当てた結果ではないだろうか。Twendee X（以下TwX）はビタミン C、コエンザイム Q10、リボフラビン、L-グルタミン、シスチン、コハク酸、フマル酸、
ナイアシンの８種類の有効成分で構成され、医薬品に求められる安全性試験を全てクリアした国際特許（PTC）、日本国特許（特許第 577782 号 細胞障害作用からの防御のための組成物）を取得した抗酸化サプ
リメントである。TwX の抗酸化効果は、生体内における酸化ストレスの制御によって生物のエネルギー産生の場であるミトコンドリアの保護、これに伴うエネルギー産生の増加、血糖値のコントロールなど、
これまでの第三者機関を含む多くの研究から明らかになりつつある。その成果の一つとして、多施設共
同無作為二重盲検プラセボ対照前向き介入試験において、ヒトの認知症の前段階、軽度認知障害（MCI）の認知症を予防することが証明された。また、加齢に伴って起こる筋力、体力低下（フレイル）の予防効
果も明らかになっている。このほか、難治性尋常性ざ瘡や花粉症、喘息、アトピー性皮膚炎、糖尿病や潰瘍性大腸炎、慢性疲労性症候群や全身性強皮症など、国民病・生活習慣病から難治性疾患までの予防効果についても明らかになりつつある。老化は長い年月によって蓄積された様々な蓄積産物によって生じ、個々によって大きく異なる。本セミナーでは TwX の酸化ストレス制御がもたらす様々な効果から、老化予防への可能性について紹介する。

－ 82 －

氏名

犬房

春彦

略歴
1982 年 3 月

近畿大学医学部卒業

1988 年 3 月

近畿大学医学部大学院外科学系修了

1988 年 4 月

米国ワシントン州立大学生化学教室 箱守仙一郎教室 研究員

1991 年 4 月

近畿大学医学部第一外科病院講師

2001 年 10 月

近畿大学医学部臨床医学部門教授・奈良キャンパス臨床栄養学教授

2004 年 4 月

ストラスブール大学欧州テレサージェリー研究所客員教授

2004 年 11 月

スペインバルセロナ大学外科学教室客員教授

2005 年 11 月

近畿大学医学部先端医療・医療経済対策室 室長

2013 年 11 月

岐阜大学科学研究基盤センター 共同研究講座 抗酸化研究部門 特任教授

2019 年 3 月

ルイ・パストゥール医学研究センター・抗酸化研究室 主席研究員

所属機関
岐阜大学高等研究院 科学研究基盤センター 共同研究講座 抗酸化研究部門
その他／受賞歴
SIPS2019 Geim International Innovation award
SIPS2022 Murad International Life Improvement Award－ 83 －

産学連携による室戸海洋深層水の利用促進に向けた取組み
福井

浩二

芝浦工業大学 システム理工学部 生命科学科 分子細胞生物学研究室

教授

ミネラルとは微量元素のことであり、主要ミネラル 7 種と微量ミネラル９種の合計 16 種が必須ミネラ
ルとして存在する。近年では、男女問わず各世代でミネラル摂取不足が起きており、重大な問題となっている。
ミネラルを摂取する方法にはサプリメントなど多様な方法が存在するが、その一つにミネラルウォー
ターやスポーツ飲料がある。ミネラルウォーターは消費量が年々増加しているが、日本で販売されている国内大手メーカーの製品はほとんどが軟水でミネラルはほとんど含まれていない。また、スポーツ飲料に含まれるミネラルの９割がナトリウムであり、糖分を多く含むことから過剰摂取が問題となっている。そこで、我々はこれらの問題を解決するために、日常的に手軽に摂取できる手段として海洋深層水に注目している。
実験に先立ち、高知県室戸岬沖から海洋深層水を採取し、ミネラル成分を濃縮、この濃縮したミネラ
ルを高知県室戸市の濾過した天然水に再溶解し、硬度 300 に調整した水を共同研究先企業が作製した。我々はこの水をマウスに投与し、モーリス水迷路装置を用いての認知能試験やトレッドミル装置によるトレー
ニング増強効果の確認試験など、様々な実験を行った。更に、ヒトに対しても１か月間の連続飲用試験を実施した。本スポンサードセミナーではこれらの実験結果について紹介する。なお、この水は、2022
年６月に室戸 301 バランスウォーターとして一般発売されている。継続的なミネラル摂取はマウスやヒトにおいて様々な有益な効果があることが分かった。我々のグループでは現在も継続して検討を重ねている。
関連文献：Nutrients, 14, 1794, 2022. doi：10.3390/nu14091794.
関連資料：

製品紹介

室戸海洋深層水について－ 84 －

福井浩二
芝浦工業大学 システム理工学部 生命科学科 分子細胞生物学研究室
教授【研究領域】ビタミンE、酸化ストレス、老化【経歴】
2003 年 ３月

芝浦工業大学大学院修了

2003 年 ４月

和歌山県立医科大学

医学部

2004 年 11 月

北海道大学大学院

2008 年 ４月

芝浦工業大学

システム理工学部

生命科学科

助教

2011 年 ４月

芝浦工業大学

システム理工学部

生命科学科

准教授

2014 年 ８月

米国国立衛生研究所（NIH）、米国国立老化研究所（NIA）Special Volunteer（2015 年８月まで）（兼任）

2017 年 ４月 ～芝浦工業大学2019 年 ４月 ～地方独立行政法人

博士（工学）取得
内科学第三講座

理学研究院

生命理学部門システム理工学部

博士研究員
助手

生命科学科

教授

東京都健康長寿医療センター研究所

協力研究員（兼務）【所属学会】
日本酸化ストレス学会（理事、学会誌委員会委員）、日本抗加齢医学会（評議員）、日本酸化ストレス学会関東支部会（副支部長）、日本基礎老化学会（評議員）、日本ビタミン学会（代議員、関東地区代表幹事、国際交流委員、トピックス等担当委員）、脂溶性ビタミン総合研究委員会（幹事）、ビタミン E 研究会（幹事）、日本栄養食糧学会、
日本農芸化学会、日本機能水学会、Society for Neuroscience【最近の学会の大会運営・組織委員】
2024 年

第 382 回 脂溶性ビタミン総合研究委員会 世話人

2024 年

第 47 回 日本基礎老化学会 大会長

2024 年

第 35 回 腎とフリーラジカル研究会 大会長

2024 年

第 77 回 日本酸化ストレス学会 プログラム委員長

2023 年

第 46 回 日本基礎老化学会 プログラム委員長

2023 年

IAGG-AOR2023（アジア・オセアニア国際老年学会）Local Organizing Committee

2022 年

第 35 回 日本酸化ストレス学会関東支部会 大会長【最近の業績】◦ Int J Artif Organs, 2024, in press, doi：10.1177/03913988241230942◦ J Clin Biochm Nutr, 74, 119-126, 2024
◦ Geriatr Gerontol Int, 24, 88-95, 2023
◦ PLoS One, 18, e0289534, 2023
◦ iScience, 26,6, 106997, 2023
◦ J Clin Biochm Nutr, 73, 24-33, 2023
◦ J Clin Biochm Nutr, 73, 1-8, 2023
◦ J Clin Biochm Nutr, 72, 93-100, 2023
【学術雑誌】◦ Journal of Clinical Biochemistry and Nutrition, Executive Editor◦ Frontiers in Molecular Neuroscience, Associate Editor◦ Advanced in Redox Research, Editorial Board Member【賞罰】
トピックス貢献賞（日本ビタミン学会、2021）、学術賞（日本酸化ストレス学会、2020）、奨励賞（日本ビタミン学会、
2013）、SFRR-Asia Young Investigator Award（SFRR-Asia，2012）、SFRR-Japan Young Investigator Award（SFRR-Japan、2009）、宮地杭一記念賞（芝浦工業大学、2006）、Student Fellowship Award（SFRR-International，2002）、奨励賞（日本基礎老化学会、2002）－ 85 －

第 47 回日本基礎老化学会大会
賛助団体
本学会大会開催にあたり、以下の企業（法人）様より協賛いただきました。
ご厚情に対し心より深く御礼申し上げます。

共催
学校法人 芝浦工業大学

協賛企業
TIMA Tokyo 株式会社株式会社北浜製作所
コンビ株式会社
株式会社タケナカ
利根化学株式会社
日本電子株式会社
富士フイルム和光純薬株式会社
雪印メグミルク株式会社
公益財団法人ルイ・パストゥール医学研究センター（50 音順）公益財団法人
精密測定技術振興財団－ 86 －

第47回日本基礎老化学会大会
プログラム・発表抄録

編集・発行

第47回日本基礎老化学会大会事務局
芝浦工業大学
システム理工学部 生命科学科 分子細胞生物学研究室〒337-8570 埼玉県さいたま市見沼区大字深作307

印刷・製本

コロニー印刷日本基礎老化学会
Japan Society for Biomedical Gerontology