bluuebunny/crossref_metadata_2025_split huggingface dataset:
AGE-RELATED DIFFERENCES IN KETONE METABOLISM: A STUDY OF KETONE ESTER RESPONSES ACROSS LIFESPAN
Authors: Hernandez Ester , Jordan Aydan , Senadheera Chatura , Stephens Elizabeth , Newman John , Kackley Madison , Volek Jeff , Stubbs Brianna 
Published: January 2025

Abstract
Ketone supplements, such as ketone esters, induce ketosis without other dietary changes and have demonstrated many potential applications in younger adults. However, metabolism by older adults is unknown. This study investigated the metabolic responses to ketone ester consumption across the lifespan, to understand how aging influences blood ketone responses. This study was an open-label, single-arm, observational study of n=82 adults (37=Male, age=20-70y). After an overnight fast, subjects consumed 360 mg/kg/lean body mass of ketone ester (bis-octanoyl-(R)-1,3-butanediol) in a beverage. Then, capillary blood samples were collected at regular intervals for 4h and beta-hydroxybutyrate (BHB) was assayed using a handheld device. Endpoints were peak BHB concentration (Cmax), area under the curve (AUC). The analysis of BHB Cmax across five decades showed no overall effect (p=0.5), with the highest Cmax in the 41-50y group (1.68 mM) and the lowest in the 51-60y group (1.32 mM). In contrast, although there was no overall difference in BHB AUC between age groups (p=0.24, mean mm.min-1, age 20-30y =184, 31-40y =194, 41-50y =221, 51-60y =203, 61-70y =223) there was a notable difference between the 21-30y and 61-70y groups (p=0.03). Linear regression analysis revealed a positive relationship between BHB AUC and age (R²=0.08, p=0.01), but not between BHB Cmax and age (R²=0.01, p=0.37). We cautiously interpret our data to suggest a relationship between increasing age and changes to ketone metabolism that increases AUC but not Cmax. We plan to expand the sample size to 400 subjects to improve our ability to detect-age related differences in exogenous ketone metabolism.
BLOOD MULTIOMIC PROFILES REFLECT SYSTEM STATES OF ORGANS IN MICE
Authors: Watanabe Kengo , Pflieger Lance , Robinson Max , Lapidus Jodi , Miller Richard , Fiehn Oliver , Moritz Robert , Rappaport Noa 
Published: January 2025

Abstract
The rate of aging can vary among organs, as evidenced by organ-specific biological age models. Such models are typically constructed based on the blood biomarkers or phenotypes that are known to be specific to a particular organ. However, this approach potentially limits the models to reflecting only a narrow scope of organ system states. Herein, we report the potential of blood omics data to reflect alterations in organ systems, using the NIA Longevity Consortium mouse prolongenvity proteomics and metabolomics data which were derived from kidney, liver, gastrocnemius muscle, and plasma samples from each mouse. While correlation analysis mainly identified the correlations of matched analytes between organs and blood, machine learning models to predict the organ analyte abundance or system state from the plasma analytes revealed the differences between sexes or prolongevity interventions. Our findings suggest the power of blood omics for identifying and characterizing diverse system states of organs involved in aging and longevity.
CARDIAC SPECIFIC OVEREXPRESSION OF SERUM RESPONSE FACTOR ALTERS MITOCHONDRIAL STRUCTURE AND FUNCTION
Authors: Patyal Pankaj , Azhar Gohar , Verma Ambika , Zhang Xiaomin , Wei Jeanne Y 
Published: January 2025

Abstract
Serum response factor (SRF) is a transcription factor required for the regulation of genes important for cardiac structure and function. Previously, we have shown that increased levels of SRF in transgenic mouse carrying human SRF under Myh6 promoter resulted in cardiomyopathy and early mortality. Although, there is a rapidly growing body of literature investigating the effects of aging on the heart and how age-related alterations affect cardiac and mitochondrial function, and underlying mechanisms remain unclear. Herein, we tested the hypothesis whether cardiac specific overexpression of SRF alters mitochondrial function. We utilized SRF transgenic mice at different postnatal ages to demonstrate temporal increase in the SRF expression in the heart. Western blot analysis demonstrate the significant increase in the BNP, marker for left ventricular cardiac hypertrophy (p &lt; 0.01). Electron microscopy revealed mitochondrial abnormalities. Further, we used high-resolution respirometry to determine mitochondrial function in SRF overexpressed mouse heart. Our data indicate the significant decrease in the mitochondrial respiratory chain complexes (I-IV) respiratory rates and maximal electron transport system capacity (p &lt; 0.01). The markers for mitochondria biogenesis PGC1α and PGC1β expression levels were reduced analyzed by western blot analysis (p &lt; 0.05). Further, protein expression levels of Opa1 and DRP1, markers for mitochondrial fusion and fission were significantly reduced (p &lt; 0.01). Our findings implicate that the increase in the SRF expression in cardiac aging induce mitochondrial alterations and functional decline. Thus, SRF is likely to be one of the downstream effectors of the signaling pathways involved in mediating mitochondrial function.
CIRCULATING MIRNA PROFILING FOR THE DETECTION OF SARCOPENIA COMPONENTS IN OLDER ADULTS
Authors: Shin Hyung Eun , Jang Jae Young , Lee Daehyun , Jung Heeeun , Cho Hyunjin , Lim Nahyun , Won Chang Won , Kim Miji 
Published: January 2025

Abstract
MicroRNAs (miRNAs), short, non-coding RNAs that regulate gene expression at translation, are recently emerging as potential biomarkers for sarcopenia. The miRNAs have been extensively studied in etiology of sarcopenia; however, the role of miRNAs on sarcopenia components has not yet been explored. We aimed to examine the differentially expressed miRNAs in plasma of older adults in relation to muscle mass, strength, and performance status. A total of 96 older adults (women: 50.0%; mean age: 76.6 ± 3.6 years) were randomly selected and matched by age and sex from the Korean Frailty and Aging Cohort Study (KFACS). Participants were categorized into four groups based on criteria of Asian Working Group for Sarcopenia 2019: “Normal” (n = 25), “Low muscle mass (LMM) only” (n = 23), “Low muscle strength (LMS) only” (n = 25), “Low physical performance (LPP) only” (n = 23). MiRNA profiles, derived from miRNA sequencing, were established via screening for differentially expressed miRNAs in four groups, and candidate differentially expressed miRNAs were validated using RT-qPCR. The miRNA profiling and validation analysis showed that three differentially expressed miRNAs, including miR-144-3p, miR-122-3p, and miR-210-3p, were significantly increased in plasma of “LMS only” group, compared to “LMM only” and “LPP only” groups (p &lt; 0.05). The Kyoto Encyclopedia of Genes and Genomes revealed that three miRNAs were mainly related to neurotrophin signaling pathway (p &lt; 0.05). These results suggest that increased levels of miR-144-3p, miR-142-3p, and miR-122-3p could serve as candidate plasma biomarkers for the decline of muscle strength in older adults.
CONFORMAL PREDICTION OF RESIDUAL COGNITION IN AGING AND ALZHEIMER’S DISEASE
Authors: Essien Ime , McDaniel Laura , Walston Jeremy , Bennett David , Abadir Peter , Chellappa Rama 
Published: January 2025

Abstract
Cognitive reserve (CR) and resilience in aging and Alzheimer’s disease (AD) have gained significant attention in recent research. We explore cognitive resilience by examining how individuals maintain cognitive function despite neuropathological burden, particularly in the context of AD in Religious Orders Study and Rush Memory and Aging Project (ROSMAP) cohort. Our approach involves modeling residual cognition, defined as the difference between observed cognitive function and expected function based on neuropathological burden. Conformal prediction is applied to generate prediction intervals for global cognitive scores based on beta-amyloid and tau protein levels and demographic data. This provides a valid measure of uncertainty to derive our residual cognition. This method allows us to identify cases where beta-amyloid and tau protein levels are misaligned with final cognitive diagnoses, providing valuable feature interpretability. The study stratifies participants using the Clinical consensus diagnosis of cognitive status at time of death into control, asymptomatic AD (AsymAD), and AD groups to investigate cognitive maintenance in the presence of AD-associated neuropathological changes. By comparing residuals across different diagnostic groups, we gain insights into factors contributing to cognitive resilience. We use the clinical diagnosis of cognitive status as a validation measure to examine how well our residual cognition measure predicts clinical outcomes. Our research builds upon previous work on CR measurement, including decomposition approaches, the Alzheimer’s Disease Cognitive Resilience Score, and the residual reserve index. The findings will help inform interventions to promote cognitive health in aging populations.
DAILY CONSUMPTION OF KETONE ESTER, BIS-OCTANOYL (R)-1,3-BUTANEDIOL, IS SAFE AND TOLERABLE IN HEALTHY OLDER ADULTS
Authors: Senadheera Chatura , Blonquist Traci , Stubbs Brianna , Diaz Stephanie Roa , Peralta Sawyer , Stephens Elizabeth , Newman John 
Published: January 2025

Abstract
Ketone bodies are endogenous metabolites produced during fasting or a ketogenic diet that have pleiotropic effects on aging pathways. Ketone esters (KEs) are compounds that induce ketosis without dietary changes, but KEs have not been studied in an older adult population. The primary objective of this pilot study was to assess tolerability and safety of KE ingestion in older adults. We carried out a randomized, placebo-controlled, double-blinded, parallel-arm trial (NCT05585762) with community-dwelling, independent older adults in stable health. N=30 (M=15, F=15; age=76y, range 65 –90y) were randomized and n=23 completed. Participants were randomly allocated to consume either KE (25g bis-octanoyl (R)-1,3-butanediol) or a taste, appearance, and calorie-matched canola oil placebo (PLA) daily for 12 weeks. Tolerability was assessed using a daily log for 2-weeks, and then via a bi-weekly phone interview. Safety was assessed by vital signs and lab tests at screening and weeks 0, 4 and 12, along with tabulation of adverse events. There was no difference in the prespecified primary outcome of proportion of participants reporting moderate or severe nausea, headache, or dizziness on more than one day in a two-week reporting period (KE n=2 (14.3% [90% CI=2.6–38.5]);PLA n=1 (7.1% [90% CI=0.4–29.7]). Dropouts numbered four in the PLA group and two in the KE group. More symptoms were reported in both groups during the first two weeks; symptoms were reported less frequently between 2–12 weeks. There were no clinically relevant changes in safety labs or vital signs in either group.
DETERMINANTS OF AGE AT NATURAL MENOPAUSE AMONG POSTMENOPAUSAL GHANAIAN WOMEN IN OKAIKWEI NORTH DISTRICT, GHANA
Authors: Kontor Okyere , Nyarko Veneranda , Botwe Paul 
Published: January 2025

Abstract
The age at natural menopause, influenced by genetic and modifiable factors is linked to the risk of certain chronic conditions. While menopause has been studied extensively in other countries, there is limited data on its determinants among women in developing countries like Ghana, creating a theory gap for investigations. This study aims to assess post-menopausal women’s knowledge of menopause, determine the average age at natural menopause, and identify factors influencing this age among postmenopausal Ghanaian women in the Okaikwei North Municipality of Ghana. A cross-sectional study design with a quantitative approach was used. Consecutive sampling selected 296 post-menopausal women attending Achimota Hospital’s (municipal referral hospital) outpatient clinic. Data were collected via a structured questionnaire and analyzed using Stata version 16. Descriptive statistics, bivariate analysis (Chi-square and Fisher’s exact test) and multiple logistic regression (crude and adjusted odds ratios) were used, with statistical significance set at p &lt; 0.05. The study found that 48.3% of participants had adequate knowledge about menopause. Most women experienced the “expected” natural menopause, 46-55 years (93.2%), with early menopause (40-45 years) at 3.7% and late menopause (&gt;55 years) at 3.1%. The average age at natural menopause was 49.5 years (±0.17 SD). Significant factors associated with natural menopausal age included age at menarche, age at first pregnancy and contraceptive use. The study highlighting low knowledge about menopause among the participants therefore recommends an enhanced practical education, cost-effective health care, and women’s empowerment to better prepare women for menopause, particularly those approaching this transition.
DIETARY METHIONINE RESTRICTION STARTED LATE IN LIFE IMPROVES NEUROMUSCULAR FUNCTION AND PROMOTES HEALTHY AGING
Authors: Parkhitko Andrey , Arciga Ulalume Hernandez , Stamenkovic Ceda , Yadav Shweta , Ables Gene , Sacco Alessandra , Jurczak Michael , Rizzo Stacey J Sukoff 
Published: January 2025

Abstract
Methionine metabolism is negatively affected by aging and restricting methionine consumption (MetR) extends lifespan across diverse species. Similarly, levels of enzymes in the tyrosine degradation pathway (TDP) increase with age, the targeting of which extends Drosophila lifespan. However, we have limited information on the effects of either metabolic manipulation when started late in life in mice, and we lack information on the effects of dietary MetR on the aging process in humans. To investigate the efficacy of targeting either methionine metabolism or the TDP for healthspan improvement in advanced age, we initiated long-term dietary MetR or treatment with the TDP inhibitor, nitisinone, in 18-mo male and female C57BL/6J mice. Our data demonstrate multiple healthspan benefits of dietary MetR started late in life with the strongest improvements observed in neuromuscular function, metabolic health, lung function, and frailty. By contrast, we observed no such signal of benefit with nitisinone treatment. Using single-nucleus RNA and ATAC sequencing of muscle tissues, we identified subtype-specific processes and transcription factors activated by dietary MetR. Epigenetic clocks can be used to evaluate longevity interventions across different species including humans. Surprisingly, dietary MetR did not significantly affect the mouse epigenetic clock. An analysis of human samples obtained from a randomized clinical trial (NCT04701346) examining an 8-week dietary MetR intervention also did not reveal a significant MetR-dependent effect on the epigenetic clocks. These findings establish beneficial effects of MetR started late in life and provide translational rationale to develop MetR mimetics as an anti-aging intervention in humans.
DIFFERENTIAL EFFECT OF SIRT1 ON MITOCHONDRIAL FUNCTION: INSIGHTS INTO MITOCHONDRIAL RESPIRATORY COMPLEXES
Authors: Zhang Xiaomin , Shrivastava Jyotsna , Patyal Pankaj , Verma Ambika , Sharma Shakshi , Azhar Gohar , Wei Jeanne Y 
Published: January 2025

Abstract
Sirtuin-1 gene (SIRT1) regulates various cellular functions that influence metabolic homeostasis and aging. SIRT1 dysfunction has been implicated in cardiovascular diseases and mitochondrial dysfunction. However, mechanism of SIRT1 in the regulation of cellular respiration, metabolic homeostasis, and mitochondrial respiratory complexes is not well-known. We tested whether SIRT1 gene knockout (KO) in HEK293T affects mitochondrial respiratory complex function and expression profiles of associated genes compared with wildtype (WT) HEK293T cells. Oxygen consumption rate (OCR, assayed by XFe96 Analyzer and Oxygraph-O2K) was reduced (p &lt; 0.001 and p &lt; 0.05, respectively) in HEK293T SIRT1-KO cells compared to WT. Basal extracellular acidification rate (ECAR) was also reduced in SIRT1-KO cells relative to WT (p &lt; 0.001), with higher levels of ATP in SIRT-1 KO (p &lt; 0.01). SIRT1-KO significantly reduced the expression of glycolytic genes, including Phosphofructokinase P (p &lt; 0.01), Hexokinase 2 (p &lt; 0.05), and Phosphofructokinase Mv4 relative to WT (p &lt; 0.05). Mitochondrial respiratory complexes are vital for ATP production through oxidative phosphorylation. Complex IV is crucial for the final step of electron transport chain. Compared to WT, significantly reduced OCR for complex IV in SIRT1-KO cells indicated mitochondrial dysfunction and impaired energy production (p &lt; 0.05). SIRT1-KO also repressed the expression of mitochondrial respiratory complex I genes (NDUFAB1, NDUFV1, and NDUFV2), essential for efficient cellular respiration. This repression suggests compromised mitochondrial bioenergetics and metabolic homeostasis. Interestingly, SIRT1-KO also downregulated mitofusin-1, a key protein in maintaining mitochondrial morphology and size. Our data highlights that SIRT1 is crucial for regulating mitochondrial respiration, metabolism, and bioenergetics.
E3 UBIQUITIN LIGASE2 SIAH2 MAY REGULATE AGE-ASSOCIATED LIPID TURNOVER IN ADIPOSE TISSUE MACROPHAGES
Authors: Ghosh Bhaswati 
Published: January 2025

Abstract
The global adult population with obesity is rapidly increasing. One of the aging hallmarks is accumulation of pro-inflammatory cells, which disrupts the balance between lipid storage and lipolysis leading to adipose tissue (AT) expansion and obesity-related insulin resistance. The primary inflammatory contributors in AT are adipose tissue macrophages (ATMs). As in obesity, ATM accumulation increases with aging. Notably, the ubiquitin-proteasome system, the non-lysosomal degradative machinery that maintains protein homeostasis, tightly regulates inflammation and declines with age. We hypothesized that aging downregulates proteasomal activity in ATMs resulting in dysfunctional lipid metabolism. We previously showed the E3-ubiquitin ligase Seven-in-Absentia mammalian homolog2 (Siah2) is crucial for promoting adipogenesis in pre-adipocytes and regulates obesity-mediated AT inflammation. Recently we found Siah2 is present in immune cells including macrophages. Here, we generated a macrophage-specific Siah2 knockout (SKM) mouse model to investigate the role of Siah2 in ATM lipid metabolism. We co-cultured primary SKM-bone marrow-derived macrophages (SKM-BMDMs) or wild-type-bone marrow-derived macrophages (WT-BMDMs) in presence of gonadal white adipose tissue from lean mice as a model of bone marrow-derived ATMs. Interestingly, SKM-ATMs accumulate more, and larger lipid droplets than WT-ATMs via increased lipid uptake. Furthermore, Siah2KO in ATMs suppresses lysosomal delivery of lipid droplets, and the SKM-ATM lysosomes are enlarged compared to WT-ATMs. Consistently, SKM-BMDMs are pro-inflammatory and show decreased oxygen consumption rate indicative of a switch to glycolytic metabolism. Altogether, our findings indicate Siah2 functions as a critical lipid sensor in ATMs, raising the possibly that aging downregulates Siah2 activity in ATMs leading to declined lipid turnover.
EARLY DIAGNOSIS OF ALZHEIMER’S DISEASE USING A SIMPLE AND SENSITIVE NANOBIOSENSOR
Authors: Xia Xiaohu 
Published: January 2025

Abstract
Existing diagnostic methods for Alzheimer’s disease (AD), such as PET/MRI imaging and cerebrospinal fluid tests, are invasive and/or costly. Recent studies have demonstrated that exosomes (nanoscale extracellular vesicles carrying specific biomarkers that can traverse blood-brain barrier) are ideal sources of AD biomarkers, which can be conveniently collected from peripheral body fluids like blood and saliva. Detection of AD exosomal biomarkers opens a new avenue for non-invasive diagnosis of AD. However, the concentrations of AD exosomal biomarkers in body fluids are extremely low. Therefore, highly sensitive analytical techniques such as mass spectrometry are required to measure the exosomal biomarkers accurately. Unfortunately, these sensitive techniques come with high costs and can be cumbersome, limiting their widespread use in clinical settings. In this research, we report a simple and low-cost nano-biosensor for ultrasensitive detection of AD exosomal biomarkers. The nano-biosensor relies on metal nanoparticles as labels or signal transducers. After conjugation of the metal nanoparticles with bioreceptors specific to AD exosomal biomarkers, the nanoparticle-bioreceptor conjugates can specifically catalyze the formation of colorimetric signal that can be conveniently quantified by an inexpensive spectrophotometer. The nano-biosensor is expected to be able to detect AD exosomal biomarkers from blood and/or saliva samples, representing a minimally invasive and accessible technology for early diagnosis of AD.
EFFECTS OF SPINELESS ON SURVIVAL AND REPRODUCTION IN DROSOPHILA MELANOGASTER
Authors: Swint Shelton , Hoffman Jessica 
Published: January 2025

Abstract
The aryl hydrocarbon receptor (AhR) is a widely conserved, ligand-activated mammalian transcription factor involved in numerous physiological processes, including maintaining stem cell pluripotency during development and regulating xenobiotic detoxification. One group of commonly studied activators of AhR are tryptophan and its downstream metabolites. Recent studies have shown that AhR-deficient mice display similar survival trends to control animals during early life (≤12 months) and then display a premature aging phenotype. As mice live for two to three years, we can advance our knowledge of AhR and aging using the fruit fly (D. melanogaster) as an alternative. Flies possess an ortholog of the mammalian AhR called spineless (ss), but the effects of ss on survival have yet to be shown. Additionally, many tryptophan-derived metabolites, like tryptamine, have been shown to decrease lifespan in control flies, potentially due to activation of AhR. We found that ss-deficient flies are shorter-lived than wildtype flies, and similar to trajectories in mice, ss flies have normal survival until around 40 days of age. The lifespan-shortening effects of tryptophan metabolites were reduced in ss-deficient flies, suggesting that the negative effects of tryptophan metabolites may be dependent on ss. Furthermore, oxidative stress assays showed that ss flies are more stress resistant, significantly outliving the wildtype flies at an early age. The effects of ss are also being investigated using a potential AhR-antagonist, cis-Jasmone. Overall, our work demonstrates that ss-deficient flies have reduced lifespan and altered responses to tryptophan metabolites, suggesting a conserved role of AhR in the aging process.