<figure><img src="image_1.png" /></figure>

HAL
open science

# Editorial: Epigenetics of metabolism, immunology and aging

Hailuan Zeng, Xiaofan Lu, Heng Sun, Haitao Wang

<figure><img src="image_2.png" /></figure>

## To cite this version:

Hailuan Zeng, Xiaofan Lu, Heng Sun, Haitao Wang. Editorial: Epigenetics of metabolism, immunology and aging. Frontiers in Genetics, 2023, 14, 10.3389/fgene.2023.1135889. [https://doi.org/10.3389/fgene.2023.1135889](https://doi.org/10.3389/fgene.2023.1135889). [hal-04743256](https://wwwHAL.fr/hal-04743256)

HAL Id: hal-04743256

https://hal.science/hal-04743256v1

Submitted on 18 Oct 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_3.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
<figure><img src="image_4.png" /></figure>

Check for updates

OPEN ACCESS

EDITED AND REVIEWED BY
Michael E Symonds,
University of Nottingham, United Kingdom

*CORRESPONDENCE

Hailuan Zeng,
 happyhellen0524@foxmail.com
Xiaofan Lu,
 xlu.cpu@foxmail.com
Heng Sun,
 hengsun@um.edu.mo
Haitao Wang,
 haitao.wang@nih.gov

SPECIALTY SECTION

This article was submitted to
Epigenomics and Epigenetics,
a section of the journal
Frontiers in Genetics

RECEIVED 02 January 2023

ACCEPTED 12 January 2023

PUBLISHED 18 January 2023

CITATION

Zeng H, Lu X, Sun H and Wang H (2023),
Editorial: Epigenetics of metabolism,
immunology and aging.
*Front. Genet.* **14**:1135889.
doi: 10.3389/fgene.2023.1135889

COPYRIGHT

© 2023 Zeng, Lu, Sun and Wang. This is an
open-access article distributed under the
terms of the Creative Commons
Attribution License (CC BY). The use,
distribution or reproduction in other
forums is permitted, provided the original
author(s) and the copyright owner(s) are
credited and that the original publication in
this journal is cited, in accordance with
accepted academic practice. No use,
distribution or reproduction is permitted
which does not comply with these terms.

Editorial: Epigenetics of
metabolism, immunology and
aging

Hailuan Zeng<sup>1,2*</sup>, Xiaofan Lu<sup>3,4*</sup>, Heng Sun<sup>5,6,7*</sup> and Haitao Wang<sup>8*</sup>

KEYWORDS

methylation, histone modification, metabolism, immune, epigenetic age, cancer

Editorial on the Research Topic

Epigenetics of metabolism, immunology and aging

The incapacitation and dysfunction of metabolism and immunity are always coupled with
aging, contributing to the development of a serial of aging-related diseases, like cancer. Previous
studies indicated that many genetic and environmental factors are involved in aging-related
diseases. Notably, these diseases are also accompanied by epigenetic changes in DNA
methylation, post-translational modifications of histones, RNA-mediated processes,
transcription factor binding, and high-order chromatin organization (Booth and Brunet
2016). Besides, increasing evidence has shown that the dysregulation of epigenetic pathways
is crucial for coordinating metabolic reprogramming and cellular immunological events in
response to extracellular stimuli, leading to and/or fueling the aging-related diseases (Cao and
Yan 2020; Sun et al., 2022). Hence, in this Research Topic, we focus on the most recent advances
that help understand the roles of epigenetics in aging, metabolism, immunology, and cancer.

The correlation of DNA CpG methylation and aging has been well studied, which serves as the basis for establishment of biological age molecular estimators, such as Horvath's pan-tissue clock and Hannum's clock (Horvath and Raj 2018; Noroozi et al., 2021). These epigenetic clocks might be affected by environmental factors, lifestyles, psychological states, and medical treatments (Noroozi et al., 2021). In the current Research Topic, Li et al. performed a genome-wide methylation study to explore the effect of metformin, a widely used drug for diabetes mellitus, on the epigenetic age of peripheral blood in patients with diabetes mellitus, and they found a strong association between metformin intake and slower epigenetic aging by Horvath's clock and Hannum's clock. In an epigenome-wide association study on biomarkers of liver function in 960 HIV-infected men, Titanji et al. identified nine DNA methylation sites annotating to *TMEM49*, *SOCS3*, *FKBP5*, *ZEB2*, and *SAMD14* genes that were positively associated with serum albumin, and reported that a higher PhenoAge score was significantly associated with a lower level of serum albumin. Moreover, by combining DNA methylation and transcriptome analysis, Wu et al. identified seven key genes that affect the occurrence and development of obesity by influencing the immune microenvironment of adipose tissue. Further, a connective map analysis of drugs suggested that four small-molecule drugs might have therapeutic effects on obesity. The study suggests that epigenetic factors could

<footnote n="1"><sup>1</sup>Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China,</footnote>

<footnote n="2"><sup>2</sup>Human Phenome Institute, Fudan University, Shanghai, China, <sup>3</sup>Department of Cancer and Functional Genomics, Institute of Genetics and Molecular and Cellular Biology, CNRS/INSERM/UNISTRA, Illkirch, France,</footnote>

<footnote n="4"><sup>4</sup>State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China, <sup>5</sup>Cancer Center, Faculty of Health Sciences, University of Macau, Macau, Macau SAR, China, <sup>6</sup>MOE Frontiers Science Center for Precision Oncology, University of Macau, Macau, Macau SAR, China, <sup>7</sup>Zhuhai Research Institute, University of Macau, Zhuhai, China, <sup>8</sup>Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute (NCI), Bethesda, MD, United States</footnote>
mediate the interaction between metabolism and immunity, thus
shedding light on identifying novel drugs targeting obesity.

In addition to DNA methylation, other epigenetic mechanisms
and technologies have been reported and used in clinical applications.
For example, long non-coding RNAs have been shown to regulate
gene expressions through recruiting, repelling, or affecting the
expression of DNA methyltransferases and TET enzymes (Huang
et al., 2022). In this Research Topic, Wang et al. performed a blood
circRNA-seq analysis on Chinese participants and identified 5 age-
related biomarkers that can be used to develop forensic age prediction
models with a mean average error less than 10 years. Zhang et al.
developed a risk model based on 11 m6A-related long non-coding
RNAs for predicting gastric cancer prognosis and sensitivity to
immune checkpoint inhibitors. Gong et al. identified eight N7-
Methylguanosine (m7G)-related prognostic genes that can be used
to categorize sepsis patients into two molecular subtypes with different
metabolic activities and immune status. Wang et al. showed that the
expression of CD146, a gene correlated with m5C RNA methylation
modification, is linked to poor prognosis in osteosarcoma and can be
used to predict response to immunotherapy. Zhao et al. evaluated the
activation status of the histone modification pathway in cervical
cancer and develop a prognostic model to predict clinical
outcomes. These studies may provide valuable insights and
potential applications for personalized treatment strategies for
heterogeneous diseases.

This Research Topic also includes reviews on different aspects of epigenetic regulations in signaling pathways and pathological processes. For example, Li et al. reviewed the regulatory mechanisms of N6-methyladenosine RNA methylation, the techniques for detecting N6-methyladenosine methylation, the role of N6-methyladenosine modification in cancer and other diseases, and the potential clinical applications. Yin et al. introduced the role of non-proteolytic ubiquitination in tumorigenesis and related signaling pathways. Sun et al. provided an overview of the role of rapamycin (TOR) signaling pathway regulator (TIPRL) in cancer development, as well as the TIPRL/protein phosphatase 2A (PP2A) axis and its epigenetic regulation. In addition, Cai et al. summarized the interactions of genetics, environmental factors, and epigenetics on knee osteoarthritis, with a focus on DNA methylation, histone modification, and non-coding RNA.

Epigenetic changes associated with the onset and progression of
aging-related diseases could serve as biomarkers for the diagnosis and
prognosis of these diseases. In this Research Topic, several studies have
investigated the role of fatty acid metabolism genes (Nie et al.),
glycometabolism (Yu et al.), and genetic variants (Zhao et al.) on the
prognosis and response to immunotherapy in various types of diseases,
including clear cell renal cell carcinoma (ccRCC), hepatocellular
carcinoma (HCC), and uveal melanoma (Liang et al.). These studies
have shown promising results in using multidisciplinary data analysis to

better understand the relationship between epigenetics and diseases, and
have the potential to lead to the development of more effective treatments
for these conditions. In particular, the findings on the epigenetic
regulation of metabolism, immunology, and cancer may improve our
understanding of the underlying causes of these diseases and potentially
improve health and longevity in individuals.

Author contributions

All authors listed have made a substantial, direct, and intellectual
contribution to the work and approved it for publication.

Funding

This work was supported by National Natural Science Foundation
of China (No. 81602587; No. 81973145; No. 82273735), Macao
Science and Technology Development Fund (FDCT) grants (0006/
2021/AGJ and 0065/2021/A), University of Macau, Multi-Year
Research Grant – General Research Grant (MYRG2022-00175-
FHS), Key R&D Program of Jiangsu Province (Social
Development) (BE2020694), and Shanghai Municipal Science and
Technology Major Project (Grant No. 2017SHZDZX01).

Acknowledgments

The editors thank all authors for their contributions to this
Research Topic, and we appreciate all reviewers for their time and
constructive comments on submitted manuscripts.

Conflict of interest

The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be
construed as a potential conflict of interest.

Publisher's note

All claims expressed in this article are solely those of the authors
and do not necessarily represent those of their affiliated
organizations, or those of the publisher, the editors and the
reviewers. Any product that may be evaluated in this article, or
claim that may be made by its manufacturer, is not guaranteed or
endorsed by the publisher.

References

Booth, L. N., and Brunet, A. (2016). The aging epigenome. *Mol. Cell* 62 (5), 728–744.
doi:10.1016/j.molcel.2016.05.013

Cao, J., and Yan, Q. (2020). Cancer epigenetics, tumor immunity, and immunotherapy.
*Trends Cancer* 6 (7), 580–592. doi:10.1016/j.trecan.2020.02.003

Horvath, S., and Raj, K. (2018). DNA methylation-based biomarkers and the epigenetic clock theory of ageing. *Nat. Rev. Genet.* 19 (6), 371–384. doi:10.1038/s41576-018-0004-3

Huang, W., Li, H., Yu, Q., Xiao, W., and Wang, D. O. (2022). LncRNA-mediated DNA
methylation: An emerging mechanism in cancer and beyond. *J. Exp. Clin. Cancer Res.* 41
(1), 100. doi:10.1186/s13046-022-02319-z

Noroozi, R., Ghafouri-Fard, S., Pisarek, A., Rudnicka, J., Spólnicka, M., Branicki, W.,
et al. (2021). DNA methylation-based age clocks: From age prediction to age reversion.
*Ageing Res. Rev.* 68, 101314. doi:10.1016/j.arr.2021.101314

Sun, L., Zhang, H., and Gao, P. (2022). Metabolic reprogramming and epigenetic modifications on the path to cancer. *Protein Cell* 13 (12), 877–919. doi:10.1007/s13238-021-00846-7