GeroScience最新文献

{"title":"Substrate stiffness dictates unique paths towards proliferative arrest in WI-38 cells.","authors":"Alyssa M Kaiser, Amirali Selahi, Wenjun Kong, J Graham Ruby","doi":"10.1007/s11357-025-01858-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01858-5","url":null,"abstract":"<p><p>Finite replicative potential is a defining feature of non-transformed somatic cells, first established by Leonard Hayflick in vitro using WI-38 human lung fibroblasts. Once proliferative capacity is exhausted due to telomere shortening, cells enter into a state called replicative senescence, which can be avoided through ectopic expression of telomerase reverse transcriptase (hTERT). As WI-38 cells approach replicative arrest, molecular pathways linked to mechanotransduction are induced, including YAP signaling, but the potential interplay between replicative lifespan and the mechanical environment of the cell remains unexplored. Here, we investigate the influence of mechanosensation on the trajectory towards replicative arrest taken by WI-38 cells by growing cells on substrates of varying stiffnesses. Matrix softening slowed proliferation, altered cellular phenotypes, and shortened proliferative lifespan while hTERT expression abrogated or reduced these responses. Our analyses of bulk and single-cell RNA-sequencing and ATAC-sequencing revealed the emergence of a unique G1 transcriptional state on soft substrates, characterized by an AP-1 transcription factor program, which failed to manifest with hTERT expression. Together, these findings reveal how the mechanical environment alters WI-38 cell proliferative lifespan and dictates unique paths towards growth arrest.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between periodontal disease and intrinsic capacity in older adults: insights from NHANES 2009-2014.","authors":"Vittorio Dibello,Silvano Quarto,Raffaele Cavalcanti,Carlo Custodero,Claudia Chiapparino,Madia Lozupone,Domenico Lafornara,Fabio Castellana,Roberta Zupo,Giuseppe Pistoia,Antonio Dibello,Antonio Daniele,Francesco Panza,Vincenzo Solfrizzi","doi":"10.1007/s11357-025-01884-3","DOIUrl":"https://doi.org/10.1007/s11357-025-01884-3","url":null,"abstract":"Periodontal disease (PD) is a chronic inflammatory condition linked to systemic health issues, yet its relationship with intrinsic capacity (IC)-a key determinant of healthy aging-remained underexplored. The present study investigated the associations between moderate/severe PD and IC domains in older adults in a cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. From the 30,468 NHANES subjects, we included participants aged ≥ 60 years with available PD and IC data. IC was assessed across five domains: locomotion, cognition, psychological well-being (depressive symptoms/anhedonia), sensory function (vision/hearing), and vitality (nutrition/weight loss). PD was classified as moderate or severe using CDC/AAP criteria. After applying exclusion criteria, 551 participants were included in the analyses. The prevalence of PD was 68.97% (moderate PD:51.91%/severe PD:15.06%). Severe PD was associated with reduced locomotion [odds ratio(OR):2.30, 95% confidence interval(CI):1.27-4.16), impaired psychological well-being (depressive symptoms) (OR:1.79, 95%CI:1.01-3.16), and sensory function (vision) (OR:2.37, 95%CI:1.24-4.56), while moderate PD was linked to reduced locomotion (OR:1.66, 95%CI:1.06-2.66) and impaired sensory function (hearing) (OR:1.93, 95%CI:1.04-3.75). Higher mean clinical attachment loss and probing pocket depth (PPD) were associated with reduced locomotion (OR:1.15, 95%CI:1.00-1.31 and OR:1.35, 95%CI:1.05-1.73, respectively). Mediation analysis indicated that multimorbidity had minimal influence on these associations, except for stroke, accounting for 13.3% of the relationship between mean PPD and locomotion. The present findings highlighted the potential role of periodontal health in maintaining overall functional capacity in older adults, underscoring the need for integrated oral and systemic health strategies in aging populations.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"56 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice.","authors":"Randy Strong,James F Nelson,Molly A Bogue,Jerry R Colca,Martin Denzel,Vivian Diaz,Brian N Finck,Vadim N Gladyshev,Steve Horvath,Nisi Jiang,Tracy Keller,Rolf F Kletzien,Ron Korstanje,Navasuja Kumar,Christiaan Leeuwenburgh,Elizabeth Fernandez,Andrzej Galecki,Brett Ginsburg,Melissa Han,Catherine Kaczorowski,Scott Leiser,Marisa Lopez-Cruzan,Ken Raj,Peter C Reifsnyder,Nadia A Rosenthal,Susanna Rosi,Anastasia Shindyapina,Peter Stacpoole,Adam B Salmon,Alexander Tyshkovskiy,Peter Walter,Malcolm Whitman,Richard A Miller,David E Harrison","doi":"10.1007/s11357-025-01881-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01881-6","url":null,"abstract":"Mice bred in 2021 were tested by the Interventions Testing Program (ITP) for possible lifespan benefits of 2BAct (2BA), dichloroacetate (DCA), Epicatechin (EPI), Forskolin (FSK), Halofuginone (HAL) and Mitoglitazone (MIT). All agents were administered in the diet ad libitum beginning at 7 months of age. In male mice, EPI increased median lifespan by ~ 5%, and HAL and MIT each increased median lifespan by ~ 9%. EPI and HAL, but not MIT, increased 90% survival. In addition to adding 3 new agents to the list of interventions identified by the ITP that extend lifespan, this report continues the strong male bias in the efficacy of life-extending drugs identified so far.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"54 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term mTOR inhibition by rapamycin improves cardiac and endothelial function in older men: a proof-of concept pilot study.","authors":"Alexander J Moody,Yubo Wu,Terry Q Romo,Wouter Koek,Jinqi Li,Leslie A Linehan,Geoffrey D Clarke,Eric Y Yang,Sara E Espinoza,Nicolas Musi,Robert J Chilton,Ellen Kraig,Dean L Kellogg","doi":"10.1007/s11357-025-01855-8","DOIUrl":"https://doi.org/10.1007/s11357-025-01855-8","url":null,"abstract":"Rapamycin (RAPA) and related mTOR-inhibitors have been shown to enhance healthy aging in animal models (2-10) and to be generally safe and tolerable in older people (11-13). However, studies to assess their effects on specific age-related pathologies in humans are limited. Since improvements in cardiovascular function with RAPA treatment have been reported in preclinical studies (5, 9, 10, 14-17), we posited that RAPA could be similarly efficacious in humans. Towards this end, we performed a pilot \"proof of concept\" trial to examine RAPA's effects on cardiovascular and endothelial functions that are known to decline with age (18, 19). We hypothesized that RAPA would elicit beneficial cardiovascular effects in men. A cohort of older male subjects with no known cardiac disease (ages 70-76 years) were enrolled in the open-label study and received 1 mg RAPA/day for 8 weeks. To assess cardiovascular function, cardiac MRI (CMR) was performed twice: prior to initiation of the intervention and again after 8 weeks of treatment. Endothelial function was examined using laser-Doppler flowmetry (LDF) by measuring cutaneous, endothelium-dependent, local thermal hyperemic responses pre-intervention and after 4 and 8 weeks of RAPA (1). In all 6 subjects, transmitral blood flow, peak flow rate, and maximal blood acceleration showed statistically significant improvements while endothelial function also improved over the 8-week course of RAPA treatment. Thus, cardiac and endothelial function improvements with RAPA were found and support future placebo-controlled studies in larger cohorts of healthy older persons as well as in patients with compromised diastolic and endothelial function (20, 21).","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"155 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging therapy versus direct endovascular thrombectomy in basilar artery occlusion stroke: a systematic review and meta-analysis.","authors":"Esra Zhubi,Azamat Bissenov,Marie Anne Engh,Réka Tóth,András Attila Horváth,Peter Hegyi,Bence Gunda","doi":"10.1007/s11357-025-01887-0","DOIUrl":"https://doi.org/10.1007/s11357-025-01887-0","url":null,"abstract":"The benefits and safety of bridging therapy in basilar artery occlusion remain unclear, although current guidelines recommend it based on weak evidence and analogy to anterior circulation strokes. This study compares bridging intravenous thrombolysis and endovascular thrombectomy versus direct endovascular thrombectomy in a larger-than-ever basilar artery occlusion Population. Embase, PubMed, Scopus, Web of Science, and Cochrane Library were systematically searched. Studies that reported 90-day functional independence (mRS: 0-2), 90-day independent ambulation (mRS: 0-3), successful recanalization, symptomatic intracranial hemorrhage, any type of intracranial hemorrhage, and 90-day mortality were included. Two reviewers independently extracted data and assessed bias using ROBINS-I. A random-effects model was used. The protocol was registered in PROSPERO (CRD42024519161). Fifty-eight studies with 9372 subjects were included in the final analysis. Bridging therapy was associated with higher 90-day functional independence (OR 1.46; 95% CI 1.22-1.76; p < 0.001) and lower 90-day mortality (OR 0.63; 95% CI 0.49-0.82; p = 0.002). No significant differences were found in recanalization rate (OR 0.97; 95% CI 0.79-1.18; p = 0.707) or symptomatic intracranial hemorrhage (OR 0.88; 95% CI 0.65-1.18; p = 0.330). Benefits were consistent across subgroups defined by stroke severity, treatment window, occlusion site, and study site. Bridging therapy for basilar artery occlusion patients leads to a higher rate of functional independence and lower mortality without increasing the rate of intracranial hemorrhage compared to direct endovascular thrombectomy consistently across all subgroups.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"80 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute bilateral central deafness following cardioembolic ischemic stroke: insights from EEG spectral and connectivity analysis.","authors":"Alessia Cacciotti,Francesca Miraglia,Giovanni Siconolfi,Francesco Iodice,Antonio Marrone,Cristiano Pecchioli,Petra Vukoja,Paolo Maria Rossini,Fabrizio Vecchio","doi":"10.1007/s11357-025-01902-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01902-4","url":null,"abstract":"Stroke is a leading cause of adult disability, with outcomes depending on the lesion's location and severity. While motor and language deficits are common, rare manifestations like central auditory dysfunction can be equally debilitating. This case report presents a 57-year-old woman who developed acute bilateral central deafness following a cardioembolic ischemic stroke. To investigate underlying mechanisms, advanced EEG analyses were conducted, including spectral power analysis and eLORETA-based functional connectivity, across key frequency bands. The Small World index was applied to evaluate changes in brain network organization over 6 weeks. Results revealed disrupted connectivity in bilateral auditory and associative cortices, with significant spectral power alterations. Alpha and gamma bands showed distinct recovery dynamics, while connectivity metrics indicated a shift toward global integration, possibly compensating for local disconnections. These findings demonstrate the utility of EEG biomarkers in monitoring post-stroke neural reorganization and support their potential role in guiding rehabilitation for sensory deficits.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"58 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying novel modifiable risk factors for ischemic stroke through phenome-wide association study and Mendelian randomization analyses in a large-scale prospective cohort.","authors":"Siyu Wu,Jialin Li,Xinyue Zhao,Jincheng Li,Shuaizhou Chen,Chengtong Zhang,Chen Suo,Yingzhe Wang,Xingdong Chen,Mei Cui,Qiuhong Man,Yanfeng Jiang","doi":"10.1007/s11357-025-01891-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01891-4","url":null,"abstract":"Despite extensive research, significant uncertainty remains regarding the associations between various risk factors and ischemic stroke (IS). This study aimed to systematically identify and validate a broad range of potential modifiable risk factors for IS. Utilizing genetic and phenotypic data from the UK Biobank (UKB; N = 418,236), we conducted a phenome-wide association study (PheWAS) and Cox regression analysis to identify modifiable factors across sociodemographics, physical measures, lifestyles, medical history, mental health, and biological assays associated with both polygenic risk scores for IS (IS-PRS) and incident IS. To assess potential causal relationships, two-sample Mendelian randomization (MR) analysis was further performed. Among the 1,023 modifiable factors examined, 145 were significantly associated with both IS-PRS and incident IS. Notably, better lung function and more computer use were associated with decreased IS risk, whereas more summer outdoor exposure, sleep-related factors, mental health factor, and facial ageing were linked to increased IS risk. The strongest association was observed for pneumonitis due to solids and liquids, with a hazard ratio (HR) and 95% confidence interval (CI) of 7.65 (7.06- 8.28). MR analysis provided further causal evidence supporting 31 of the identified risk factors and confirmed the casual associations of worse lung function, greater summer outdoor exposure and longer daytime napping with increased IS risk. The study comprehensively identified a wide range of novel modifiable risk factors for IS, including physical, lifestyle, and mental health indicators. These findings may contribute to the development of more targeted and effective prevention strategies for IS.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"2 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145077795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longevity through immunity: the unusual naked mole-rat immune system.","authors":"Tanvi T Patel,Rileigh Rubar,Vince G Amoroso,Martha A Delaney,Thomas J Park,Rochelle Buffenstein","doi":"10.1007/s11357-025-01874-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01874-5","url":null,"abstract":"Naked mole-rats (NMR, Heterocephalus glaber) defy Gompertzian rules of mortality and age-dependent senescence to lead healthy lives well into their fourth decade. The NMR immune system likely contributes to this phenotype by protecting against infections, regulating tissue repair, and eradicating neoplastic cells. In keeping with their many other paedomorphic traits, adult NMRs retain functional thymic tissue in the submandibular triangle. Despite this additional thymic tissue, perinatal NMR thymi are half the size of mouse thymi, yet both species show similar thymic involution trajectories. Smaller thymi may indicate less diverse thymocyte clonotypes that need to complete selection before being released as functional, self-tolerant T cells. Transcriptomic studies revealed that when compared with mice, NMRs have a larger myeloid to lymphoid ratio, lack natural killer (NK) cells, and that the αβ clonotypic diversity of NMR CD8 T cells is limited and smaller than that of their CD4 T cells. NMRs, strikingly, have a large circulating population of γδ T cells with two distinct subsets; one with a large diversity of γ and δ TCR loci and the other, a cytotoxic T cell subset with a dominant clonotype. Collectively, these data suggest that NMRs, living in a sealed milieu, rely more upon the innate immune response and have evolved under relaxed viral selective pressure. Rather, they have selected for an atypical myeloid-biased mode of innate immune surveillance and circulating populations of cytotoxic γδ T cells. In summary, the NMR appears to have been optimized to provide better immunosurveillance, tissue homeostasis, and protection against cancer rather than protection against unlikely environmental exposure to viral pathogens. These features likely contribute to their prolonged healthspan and exceptional longevity.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"72 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-traumatic stress disorder, depressive symptoms, and cognitive function among middle-aged urban adults: Healthy Aging in Neighborhoods of Diversity across the Life Span study.","authors":"Michael F Georgescu,May A Beydoun,Robert H Pietrzak,Hind A Beydoun,Nicole Noren Hooten,Sri Banerjee,Michele K Evans,Alan B Zonderman","doi":"10.1007/s11357-025-01825-0","DOIUrl":"https://doi.org/10.1007/s11357-025-01825-0","url":null,"abstract":"Post-traumatic stress disorder (PTSD) and depressive symptoms Have been linked to cognitive functioning. However, the impact of PTSD and depression on cognitive functioning, especially among middle-aged urban adults, is not well understood. Cross-sectional data were analyzed from 1434 participants from the Healthy Aging in Neighborhoods of Diversity across the Life Span study. We used multivariable adjusted linear regression and structural equation models (SM) to test the association between PTSD, CES-D, and cognitive test scores. We found PTSD to be strongly associated with depressive symptoms despite adjustment for potential confounders. SM with cognitive test scores as final outcomes found Delayed Free Recall and List A immediate recall inversely associated with PTSD score, with TEs of β ± SE - 0.08398 ± 0.02654, P = 0.002, and β ± SE - 0.10734 ± 0.02571, P < 0.001, respectively, and IEs of β ± SE - 0.06786 ± 0.02202, P = 0.002, and β ± SE - 0.07625 ± 0.02140, P < 0.001, indicating that depressive symptoms significantly mediated the potential association of PTSD with poorer verbal memory. Other cognitive test scores showed significant total or direct effects (p < 0.05), suggesting different pathways not including depressive symptoms as a mediator. At higher intima-media thickness (IMT) tertiles, PTSD score was strongly associated with total CES-D score. This study provides evidence of an association between PTSD and cognitive functioning among middle-aged urban adults, partially mediated through depressive symptoms in verbal memory, with IMT enhancing the association between PTSD and depressive symptoms.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"46 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A genome-wide association study identifies Asian-specific genetic susceptibility for epigenetic age acceleration.","authors":"Kwangyeon Oh,Dabin Yun,Soyoun Yang,Minju Yuk,Changgyu Lee,Boyoung Kim,Suyeon Heo,Qian Dong,Zhaoming Wang,Hanseul Park,Nan Song","doi":"10.1007/s11357-025-01885-2","DOIUrl":"https://doi.org/10.1007/s11357-025-01885-2","url":null,"abstract":"Genome-wide association studies (GWASs) have been performed on multiple epigenetic clocks to understand the genetic underpinnings of epigenetic age acceleration (EAA). To explore ethnic differences and individual variability in Asian populations, we conducted a GWAS of EAA using multiple epigenetic clocks in the Korean population. Genome-wide single-nucleotide polymorphism (SNP) and methylation data were obtained from 1962 Korean individuals. Five epigenetic clocks (Hannum, DNAm PhenoAge, GrimAge, Zhang2019, and Horvath-Skin&Blood) were considered. GWASs, as well as gene-based, pathway enrichment, quantitative real-time polymerase chain reaction, and quantitative trait loci analyses, were performed to investigate the biological mechanisms. Pleiotropy analyses and drug repurposing were used to explore clinical implications. Six SNPs were independently associated with EAAs (P < 5 × 10-8). The DNAm PhenoAge-EAA was associated with ASPA and SPATA22 (P < 2.66 × 10-6), involved in Canavan disease and apoptosis, and the Zhang2019 was associated with ENO2, GNB3, USP5, TPI1, and CDCA3 (P < 2.66 × 10-6), which are implicated in monosaccharide catabolism. Particularly, the expression levels of SPATA22, ENO2, USP5, and TPI1 increased in senescent cells. EAA-associated genes showed strong affinities with GW0742, a peroxisome proliferator-activated receptor-β/δ (PPAR-β/δ) agonist. In addition, the Zhang2019-EAA-associated SNP showed pleiotropy in liver function biomarkers, including iron and bilirubin. We identified six Asian-specific EAA-associated genetic variants, including five novel SNPs. The novel SNPs, which are rare in European populations, could implicate ancestry-related genetic differences in epigenetic aging. Furthermore, the genetic implications of the DNAm PhenoAge-EAA and Zhang2019-EAA on apoptosis and liver function may contribute to a better understanding of EAA in East Asian populations.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"46 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}