GeroScience最新文献

{"title":"EnsembleAge: enhancing epigenetic age assessment with a multi-clock framework.","authors":"Amin Haghani,Ake T Lu,Qi Yan,Juan Carlos Izpisua Belmonte,Pradeep Reddy,Victor Cheng,X William Yang,Nan Wang,Khyobeni Mozhui,Kevin Murach,Alejandro Ocampo,Robert W Williams,Mathias Jucker,Carina Bergmann,Jesse R Poganik,Bohan Zhang,Vadim N Gladyshev,Steve Horvath","doi":"10.1007/s11357-025-01808-1","DOIUrl":"https://doi.org/10.1007/s11357-025-01808-1","url":null,"abstract":"Several widely used epigenetic clocks have been developed for mice and other species, but a persistent challenge remains: different mouse clocks often yield inconsistent results. To address this limitation in robustness, we present EnsembleAge, a suite of ensemble-based epigenetic clocks. Leveraging data from over 200 perturbation experiments across multiple tissues, EnsembleAge integrates predictions from multiple penalized models. Empirical evaluations demonstrate that EnsembleAge outperforms existing clocks in detecting both pro-aging and rejuvenating interventions. Furthermore, we introduce EnsembleAge HumanMouse, an extension that enables cross-species analyses, facilitating translational research between mouse models and human studies. Together, these advances underscore the potential of EnsembleAge as a robust tool for identifying and validating interventions that modulate biological aging.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"26 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787023","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":"Mitochondrial dysfunction in peripheral mononuclear blood cells (PBMC) of individuals with mild cognitive impairment.","authors":"Fabian Dieter,Karlotta Jacobs,Alice Quentin,David Prvulovic,Andreas Reif,Johannes Pantel,Ulrich Pilatus,Elke Hattingen,Silke Matura,Gunter Peter Eckert","doi":"10.1007/s11357-025-01813-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01813-4","url":null,"abstract":"Mitochondrial dysfunction is a hallmark of aging and many age-related neurodegenerative diseases. Mild cognitive impairment (MCI) refers to a clinical condition characterized by noticeable cognitive decline that exceeds normal age-related changes but does not significantly interfere with daily functioning. MCI is often considered an early stage of neurodegenerative conditions, including Alzheimer's disease. We therefore investigated the relationship between mitochondrial function in peripheral blood cells and cognitive performance in individuals with amnestic (aMCI) and nonamnestic mild cognitive impairment (naMCI). Control groups consisted of young (YC) and older adults (OC) who were physically and mentally healthy. Cross-sectional observational study involving 90 participants, including young adults, cognitively healthy older adults, and individuals with MCI. Mitochondrial function was determined in cryopreserved PBMCs. Cognitive status was assessed using the German version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery. ATP levels in cryopreserved PBMC isolated from individuals with aMCI were significantly lower than those of OC and YC. Endogenous respiration varied significantly between groups, with the MCI group exhibiting the lowest respiration. Linear regression analyses with ATP as a predictor for cognitive performance showed a significant positive relationship between ATP levels and both immediate recall and fluency. The regression coefficients indicated a moderate positive correlation between ATP levels and performance in both tests. This suggests that higher ATP levels are associated with improved cognitive performance. Our data suggest that mitochondrial dysfunction in PBMC is associated with MCI and correlates with cognitive impairment. Subjects who performed poorly on neuropsychological tests also exhibited lower ATP levels. Given that PBMC are easily accessible, they offer valuable insights into the bioenergetic status of individuals at increased risk for dementia. The study (PEM-MCI) has been retrospectively registered at the German Register of Clinical Trials (DRKS) DRKS00036017 (registered on 30.01.2025).","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"52 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791873","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":"The senescence-inhibitory p53 isoform Δ133p53α: enhancing cancer immunotherapy and exploring novel therapeutic approaches for senescence-associated diseases.","authors":"Shinji Nakamichi,Leo Yamada,Christopher Roselle,Izumi Horikawa,Carl H June,Curtis C Harris","doi":"10.1007/s11357-025-01819-y","DOIUrl":"https://doi.org/10.1007/s11357-025-01819-y","url":null,"abstract":"Δ133p53α is a naturally occurring isoform of the tumor suppressor protein p53. Δ133p53α functions as a physiological dominant-negative inhibitor of the full-length p53 protein (commonly referred to as p53). Δ133p53α preferentially inhibits p53-mediated cellular senescence, while it does not inhibit, or may even promote, p53-mediated DNA repair. Owing to this selective inhibitory activity that preserves genome stability, Δ133p53α represents a promising target for enhancement in the prevention and treatment of diseases associated with increased senescence of normal cells. These diseases include Alzheimer's and other neurodegenerative diseases, premature aging diseases such as Hutchinson-Gilford progeria syndrome (HGPS), and idiopathic pulmonary fibrosis (IPF). Current cell-based therapies, which are limited by increased cellular senescence, may also benefit from Δ133p53α-mediated improvements. As an initial application of Δ133p53α in improving therapeutic cells, we here introduce Δ133p53α-armored chimeric antigen receptor (CAR)-T cells. Based on our previous and ongoing studies using various types of senescent human cells in vitro, we also discuss the importance of further exploring the therapeutic potentials of Δ133p53α, with particular focus on HGPS and IPF. The development of mouse models facilitates in vivo evaluation of the therapeutic effects of Δ133p53α, potentially leading to future clinical applications.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"34 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144791989","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":"Chronic inflammation mediates the relationship between physical activity and telomere length.","authors":"Anamika Nanda,Daniel H Aslan,M Katherine Sayre,Pradyumna K Bharadwaj,Madeline Ally,Hyun Song,Amit Arora,Silvio Maltagliati,Mark H C Lai,Rand R Wilcox,Yann C Klimentidis,Gene E Alexander,David A Raichlen","doi":"10.1007/s11357-025-01818-z","DOIUrl":"https://doi.org/10.1007/s11357-025-01818-z","url":null,"abstract":"A physically active lifestyle benefits cellular aging, however the mechanisms linking physical activity (PA) with longevity remain unclear. PA is associated with longer telomere length (TL), while shorter TL has been associated with increased cellular aging. Some research suggests increased levels of inflammatory markers, such as C-reactive protein (CRP), are associated with telomere dysfunction. We tested the hypothesis that CRP levels mediate the association between PA and TL. Using data from the UK Biobank, we analyzed adjusted leukocyte T/S ratio (relative telomere to single gene copy), serum CRP, and moderate-to-vigorous physical activity (MVPA) data via device-measured actigraphy. We applied general linear regressions and a causal mediation analysis with 10,000 bootstraps while controlling for a range of covariates (age, BMI, smoking status, sex, ethnicity, time between data collection, time wearing the accelerometer, and the Townsend Deprivation Index). Variables of interest were transformed to approximate normality. A total of 79,873 participants were included in the final analytic sample. MVPA and CRP were both significant predictors of TL (βMVPA = 3.03e - 03 [95%CI = 1.58e - 03, 4.47e - 03], pMVPA = 4.10e - 05; βCRP =  - 1.36e - 03 [95%CI =  - 1.87e - 03, - 8.40e - 04], pCRP = 2.52e - 07, respectively). The association between MVPA and TL was mediated by CRP, accounting for 8.65% [95% CI: 4.77%, 16.0%] of the total effect (β [95%CI] = 3.31e - 03 [1.84e - 03, 4.75e - 03], p < 2e - 16). Our analysis supports the hypothesis that CRP mediates the relationship between MVPA and TL. These novel findings suggest a potential pathway where PA is associated with lower CRP concentrations, which in turn is associated with longer average TL.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"32 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777755","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":"Midlife aging and performance study (MAPS): evaluating biological aging through a physical capacity battery.","authors":"Roy Tzemah-Shahar,Ilona Shapiro,Einat Kodesh,Merav Asher,Yechiel Friedlander,Hagit Hochner,Maayan Agmon","doi":"10.1007/s11357-025-01803-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01803-6","url":null,"abstract":"Aging is a risk factor for the development of chronic diseases; however, it is heterogeneous. Measuring aging in midlife, commonly done using laboratory markers and statistical methods for estimation of biological age (BA), cannot directly inform behavioral intervention goals aiming to promote healthier aging. The Midlife Aging and Performance Study (MAPS) examined the association between an extended, inclusive assessment of physical capacity (PC), as a behavioral marker of aging, and BA, estimated using the Klemera-Doubal method from 11 laboratory and physiological biomarkers, in 112 individuals aged 42-46 (47% women). PC was comprehensively measured by a battery covering five domains: muscle strength, endurance, balance, agility and flexibility. Better performance in strength, endurance, balance, and flexibility domains was correlated with younger BA (Pearson's r 0.33-0.49, p < 0.001). A lower composite PC score based on all five domains was significantly associated with an accelerated aging state in which BA was greater than chronological age. In a logistic regression, a composite PC score had an odds ratio of 0.40 (95% CI 0.25-0.64), demonstrating each incremental rise in PC corresponds with a 60% odds reduction of being in an accelerated aging state. The proposed PC battery could be used as a functional behavioral assessment for aging state, relevant for population wide risk-screening assessments, communicating intervention goals, and as a means to evaluate temporal changes in health, independent of laboratory tests.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"27 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787157","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":"Treatment of age-related decreases in GTP levels restores endocytosis and autophagy.","authors":"R A Santana, J M McWhirt, G J Brewer","doi":"10.1007/s11357-025-01786-4","DOIUrl":"10.1007/s11357-025-01786-4","url":null,"abstract":"<p><p>Age-related declines in neuronal bioenergetic levels may limit vesicular trafficking and autophagic clearance of damaged organelles and proteins. Age-related ATP depletion would impact cognition dependent on ionic homeostasis, but limits on proteostasis powered by GTP are less clear. We used neurons isolated from aged 3xTg-AD Alzheimer's model mice and a novel genetically encoded fluorescent GTP sensor (GEVAL) to evaluate live GTP levels in situ. We report an age-dependent reduction in ratiometric measurements of free/bound GTP levels in living hippocampal neurons. Free GTP colocalized in the mitochondria decreased with age accompanied by the accumulation of free GTP-labeled vesicular structures. The energy dependence of autophagy was demonstrated by depletion of GTP with rapamycin stimulation, while bafilomycin inhibition of autophagy raised GTP levels. Twenty-four-hour supplementation of aged neurons with the NAD precursor nicotinamide and the Nrf2 redox modulator EGCG restored GTP levels to youthful levels and mobilized endocytosis and lysosomal consumption for autophagy via the respective GTPases Rab7 and Arl8b. This vesicular mobilization promoted the clearance of intraneuronal Aβ aggregates, improved viability, and lowered protein oxidative nitration in AD model neurons. Our results reveal age- and AD-related neuronal GTP energy deficits that impair autophagy and endocytosis. GTP deficits were remediated by an external NAD precursor together with a Nrf2 redox modulator which suggests a translational path.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768612","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":"Correction to: Impaired brain ability of older adults to transit and persist to latent states with well‑organized structures at wakeful rest.","authors":"Zijin Liu, Haishuo Xia, Antao Chen","doi":"10.1007/s11357-024-01437-0","DOIUrl":"10.1007/s11357-024-01437-0","url":null,"abstract":"","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"6107"},"PeriodicalIF":5.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Biomarkers of cellular senescence and major health outcomes in older adults.","authors":"Steven R Cummings, Li-Yung Lui, Zaira Aversa, Theresa Mau, Roger A Fielding, Elizabeth J Atkinson, Sheena Patel, Nathan LeBrasseur","doi":"10.1007/s11357-025-01619-4","DOIUrl":"10.1007/s11357-025-01619-4","url":null,"abstract":"","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"6117"},"PeriodicalIF":5.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Improvement in Th1/Th2 immune homeostasis, antioxidative status and resistance to pathogenic E. coli on consumption of probiotic Lactobacillus rhamnosus fermented milk in aging mice.","authors":"Rohit Sharma, Rajeev Kapila, Gulshan Dass, Suman Kapila","doi":"10.1007/s11357-024-01385-9","DOIUrl":"10.1007/s11357-024-01385-9","url":null,"abstract":"","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"6127"},"PeriodicalIF":5.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142463214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Association between cognitive reserve proxies and frailty phenotype: data from UK Biobank.","authors":"Laura Lorenzo-Lopez, Nuria Cibeira, Ali Hemadeh, Rocío Lopez-Lopez, Carlota Lema-Arranz, Ana Maseda, Natalia Fernandez-Bertolez, Solange Costa, Eduardo Pásaro, Vanessa Valdiglesias, José C Millan-Calenti, Blanca Laffon","doi":"10.1007/s11357-025-01588-8","DOIUrl":"10.1007/s11357-025-01588-8","url":null,"abstract":"","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":"6109-6110"},"PeriodicalIF":5.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}