{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T13:06:19Z","timestamp":1776258379119,"version":"3.50.1"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Exercise is known to exert systemic effects associated with improved cardiovascular fitness and epigenetic modifications. However, the relationships between systemic epigenetic markers and physical fitness indicators remain insufficiently characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In the present study, the Illumina MethylationEPIC array (~730,000 CpG sites) was used to investigate associations between blood DNA methylation and key continuous fitness indicators-estimated VO\u2082max, grip strength, and vertical jump height-in a cohort of healthy adults. Epigenome-wide association analyses were adjusted for age, sex, estimated blood cell composition, and multiple testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No significant single-CpG associations were identified after rigorous adjustment. However, when participants were stratified into groups based on age- and sex-specific VO\u2082max norms, three CpG sites demonstrated differential methylation at a false discovery rate threshold (FDR &amp;lt; 0.05). These included cg21308111 in TNFRSF10A and cg17890932 in USP24, both showing higher methylation in lower-fitness groups, and an intergenic CpG site (cg02967877) exhibiting the opposite pattern. Region-based analyses further identified several differentially methylated regions (DMRs) between fitness groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings suggest that variation in cardiorespiratory fitness may be associated with subtle alterations in blood DNA methylation, particularly at loci related to metabolic regulation, inflammatory pathways, and intercellular communication. These findings shouldbe considered hypothesis-generating and require confirmation in larger, independent cohorts and, ideally, in longitudinal or intervention studies to elucidate more directly how changes in physical fitness relate to changes in DNA methylation patterns.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1713760","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:02:10Z","timestamp":1776254530000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenome-wide exploratory study of blood DNA methylation and markers of physical performance indicates subtle differences across levels of cardiovascular fitness"],"prefix":"10.3389","volume":"17","author":[{"given":"Ferenc","family":"Torma","sequence":"first","affiliation":[{"name":"Research Center for Molecular Exercise Science, Hungarian University of Sports Science","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emerson","family":"Santos","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics and Neurogenetics, Experimental Multiuser Laboratory (LaBiN\/LEM), Graduate Program in Health Sciences, School of Medicine and Life Sciences, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR)","place":["Curitiba, Paran\u00e1, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1ty\u00e1s","family":"J\u00f3kai","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Exercise Science, Hungarian University of Sports Science","place":["Budapest, Hungary"]},{"name":"Hungarian Wrestling Academy \u201cKozma Istv\u00e1n\u201d","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zs\u00f3fia","family":"B\u00e1bszky","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Exercise Science, Hungarian University of Sports Science","place":["Budapest, Hungary"]},{"name":"Hungarian Wrestling Academy \u201cKozma Istv\u00e1n\u201d","place":["Budapest, Hungary"]},{"name":"School of Doctoral Studies, Hungarian University of Sports Science","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gergely","family":"B\u00e1bszky","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Exercise Science, Hungarian University of Sports Science","place":["Budapest, Hungary"]},{"name":"Hungarian Wrestling Academy \u201cKozma Istv\u00e1n\u201d","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soroosh","family":"Mozaffaritabar","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Exercise Science, Hungarian University of Sports Science","place":["Budapest, Hungary"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto H.","family":"Herai","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics and Neurogenetics, Experimental Multiuser Laboratory (LaBiN\/LEM), Graduate Program in Health Sciences, School of Medicine and Life Sciences, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1 (PUCPR)","place":["Curitiba, Paran\u00e1, Brazil"]},{"name":"Research Division, Buko Kaesemodel Institute (IBK)","place":["Curitiba, Paran\u00e1, Brazil"]},{"name":"Research Division, 9p Brazil Association (A9pB)","place":["Santa Maria, Rio Grande do Sul, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo A.","family":"Pinho","sequence":"additional","affiliation":[{"name":"Laboratory of Exercise Biochemistry in Health, Graduate Program in Health Sciences, School of Medicine, Pontif\u00edcia Universidade Cat\u00f3lica do Paran\u00e1","place":["Curitiba, Paran\u00e1, Brazil"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitsuru","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Faculty of Sport Sciences, Waseda University","place":["Saitama, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaodong","family":"Gu","sequence":"additional","affiliation":[{"name":"Faculty of Sport Science, Ningbo University","place":["Ningbo, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zsolt","family":"Rad\u00e1k","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Exercise Science, Hungarian University of Sports Science","place":["Budapest, Hungary"]},{"name":"Faculty of Sport Sciences, Waseda University","place":["Saitama, Japan"]},{"name":"Institute of Sport Sciences and Physical Education, Faculty of Sciences, University of P\u00e9cs","place":["P\u00e9cs, Hungary"]},{"name":"Department of Bioengineering, Sapientia Hungarian University of Transylvania","place":["Miercurea Ciuc, Romania"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/s12902-024-01745-8","article-title":"The effects of supervised aerobic training on dyslipidaemia among diabetic older patients","volume":"24","author":"Alghadir","year":"2024","journal-title":"BMC Endocr. Disord."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5076858","DOI":"10.1155\/2020\/5076858","article-title":"Elevated serum TNF-alpha is related to obesity in type 2 diabetes mellitus and is associated with glycemic control and insulin resistance","volume":"2020","author":"Alzamil","year":"2020","journal-title":"J. Obes."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1093\/bioinformatics\/btu049","article-title":"Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays","volume":"30","author":"Aryee","year":"2014","journal-title":"Bioinformatics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s11154-022-09758-1","article-title":"Endocrine responses of the stress system to different types of exercise","volume":"24","author":"Athanasiou","year":"2023","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1280","DOI":"10.1093\/bioinformatics\/bts124","article-title":"CpGassoc: an R function for analysis of DNA methylation microarray data","volume":"28","author":"Barfield","year":"2012","journal-title":"Bioinformatics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1017\/S1355617721000394","article-title":"Exercise, arterial stiffness, and cerebral vascular function: potential impact on brain health","volume":"27","author":"Barnes","year":"2021","journal-title":"J. Int. Neuropsychol. Soc"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2024.112579","article-title":"The effect of physical exercise on circulating neurotrophic factors in healthy aged subjects: a meta-analysis and meta-regression","volume":"196","author":"Behrad","year":"2024","journal-title":"Exp. Gerontol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0270132","article-title":"Validity and reliability of handgrip dynamometry in older adults: a comparison of two widely used dynamometers","volume":"17","author":"Benton","year":"2022","journal-title":"PloS One"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.2147\/CIA.S194543","article-title":"Grip strength: an indispensable biomarker for older adults","volume":"14","author":"Bohannon","year":"2019","journal-title":"Clin. Interv Aging"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1152\/jappl.1999.87.3.1003","article-title":"Familial aggregation of VO(2max) response to exercise training: results from the HERITAGE Family Study","volume":"87","author":"Bouchard","year":"1999","journal-title":"J. Appl. Physiol. (1985)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1136\/bjsm.2003.005389","article-title":"Reliability and validity of measures taken during the Chester step test to predict aerobic power and to prescribe aerobic exercise","volume":"38","author":"Buckley","year":"2004","journal-title":"Br. J. Sports Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"3092","DOI":"10.1001\/jama.290.23.3092","article-title":"Cardiorespiratory fitness in young adulthood and the development of cardiovascular disease risk factors","volume":"290","author":"Carnethon","year":"2003","journal-title":"JAMA"},{"key":"B13","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1093\/eurheartj\/ehw249","article-title":"The association between physical activity and risk of mortality is modulated by grip strength and cardiorespiratory fitness: evidence from 498\u2013135 UK-Biobank participants","volume":"38","author":"Celis-Morales","year":"2017","journal-title":"Eur. Heart J."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glae071","article-title":"Young plasma rejuvenates blood DNA methylation profile, extends mean lifespan, and improves physical appearance in old rats","volume":"79","author":"Chiavellini","year":"2024","journal-title":"J. Gerontol A. Biol. Sci. Med. Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1152\/japplphysiol.00237.2022","article-title":"Exercise training modifies the whole blood DNA methylation profile in middle-aged and older women","volume":"134","author":"da Silva Rodrigues","year":"2023","journal-title":"J. Appl. Physiol. (1985)"},{"key":"B16","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.ahj.2017.08.022","article-title":"Cardiorespiratory fitness versus physical activity as predictors of all-cause mortality in men","volume":"196","author":"Davidson","year":"2018","journal-title":"Am. Heart J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"20166","DOI":"10.1038\/s41598-022-24642-3","article-title":"Epigenome-wide association study of physical activity and physiological parameters in discordant monozygotic twins","volume":"12","author":"Duncan","year":"2022","journal-title":"Sci. Rep."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4570","article-title":"Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis","volume":"366","author":"Ekelund","year":"2019","journal-title":"BMJ"},{"key":"B19","doi-asserted-by":"publisher","first-page":"5457","DOI":"10.1158\/1078-0432.CCR-09-1125","article-title":"Epigenetic silencing of death receptor 4 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance in gliomas","volume":"15","author":"Elias","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/j.ahj.2015.02.023","article-title":"The association between cardiorespiratory fitness and cardiovascular risk may be modulated by known cardiovascular risk factors","volume":"169","author":"Erez","year":"2015","journal-title":"Am. Heart J."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13828","article-title":"Physical activity is associated with slower epigenetic ageing-findings from the Rhineland study","volume":"22","author":"Fox","year":"2023","journal-title":"Aging Cell"},{"key":"B22","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s12915-024-01938-6","article-title":"DNA methylation of exercise-responsive genes differs between trained and untrained men","volume":"22","author":"Geiger","year":"2024","journal-title":"BMC Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1007\/s10522-024-10177-9","article-title":"The protein cargo of extracellular vesicles correlates with the epigenetic aging clock of exercise sensitive DNAmFitAge","volume":"26","author":"Gyorgy","year":"2025","journal-title":"Biogerontology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.2337\/db09-1200","article-title":"Cardiorespiratory fitness and insulin sensitivity in overweight or obese subjects may be linked through intrahepatic lipid content","volume":"59","author":"Haufe","year":"2010","journal-title":"Diabetes"},{"key":"B25","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1126\/science.aaw2622","article-title":"Blood factors transfer beneficial effects of exercise on neurogenesis and cognition to the aged brain","volume":"369","author":"Horowitz","year":"2020","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-13-86","article-title":"DNA methylation arrays as surrogate measures of cell mixture distribution","volume":"13","author":"Houseman","year":"2012","journal-title":"BMC Bioinf."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adt4258","article-title":"Deubiquitinase USP24 activated by IL-6\/STAT3 enhances PD-1 protein stability and suppresses T cell antitumor response","volume":"11","author":"Hsieh","year":"2025","journal-title":"Sci. Adv."},{"key":"B28","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1093\/ije\/dyr238","article-title":"Bump hunting to identify differentially methylated regions in epigenetic epidemiology studies","volume":"41","author":"Jaffe","year":"2012","journal-title":"Int. J. Epidemiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"2805","DOI":"10.1007\/s11357-023-00826-1","article-title":"DNA methylation clock DNAmFitAge shows regular exercise is associated with slower aging and systemic adaptation","volume":"45","author":"Jokai","year":"2023","journal-title":"Geroscience"},{"key":"B30","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/s41420-023-01544-5","article-title":"Dysregulation of a lncRNA within the TNFRSF10A locus activates cell death pathways","volume":"9","author":"Kaczynski","year":"2023","journal-title":"Cell. Death Discov."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/j.mayocp.2015.07.026","article-title":"Reference standards for cardiorespiratory fitness measured with cardiopulmonary exercise testing: data from the Fitness Registry and the Importance of Exercise National Database","volume":"90","author":"Kaminsky","year":"2015","journal-title":"Mayo Clin. Proc."},{"key":"B32","doi-asserted-by":"publisher","first-page":"E912","DOI":"10.1152\/ajpendo.00289.2014","article-title":"Exercise training alters DNA methylation patterns in genes related to muscle growth and differentiation in mice","volume":"308","author":"Kanzleiter","year":"2015","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a016824","article-title":"Synaptic signaling in learning and memory","volume":"8","author":"Kennedy","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1136\/bjsports-2013-093347","article-title":"All-cause and disease-specific mortality among male, former elite athletes: an average 50-year follow-up","volume":"49","author":"Kettunen","year":"2015","journal-title":"Br. J. Sports Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"5039","DOI":"10.1016\/j.cell.2025.05.021","article-title":"Senescence-resistant human mesenchymal progenitor cells counter aging in primates","volume":"188","author":"Lei","year":"2025","journal-title":"Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s13062-023-00395-5","article-title":"USP24-dependent stabilization of Runx2 recruits a p300\/NCOA3 complex to transactivate ADAMTS genes and promote degeneration of intervertebral disc in chronic inflammation mice","volume":"18","author":"Li","year":"2023","journal-title":"Biol. Direct"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2022.111951","article-title":"Longitudinal association of handgrip strength with all-cause and cardiovascular mortality in older adults using a causal framework","volume":"168","author":"Lopez-Bueno","year":"2022","journal-title":"Exp. Gerontol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"303","DOI":"10.18632\/aging.101684","article-title":"DNA methylation GrimAge strongly predicts lifespan and healthspan","volume":"11","author":"Lu","year":"2019","journal-title":"Aging (Albany NY)"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1378680","article-title":"Epigenome-wide association study identifies DNA methylation loci associated with handgrip strength in Chinese monozygotic twins","volume":"12","author":"Luo","year":"2024","journal-title":"Front. Cell Dev. Biol."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2018.3605","article-title":"Association of cardiorespiratory fitness with long-term mortality among adults undergoing exercise treadmill testing","volume":"1","author":"Mandsager","year":"2018","journal-title":"JAMA Netw. Open"},{"key":"B41","doi-asserted-by":"publisher","first-page":"3904","DOI":"10.18632\/aging.204538","article-title":"DNAmFitAge: biological age indicator incorporating physical fitness","volume":"15","author":"McGreevy","year":"2023","journal-title":"Aging (Albany NY)"},{"key":"B42","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.amjcard.2009.04.057","article-title":"Effect of habitual aerobic exercise on body weight and arterial function in overweight and obese men","volume":"104","author":"Miyaki","year":"2009","journal-title":"Am. J. Cardiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1093\/bioinformatics\/btt684","article-title":"ChAMP: 450k chip analysis methylation pipeline","volume":"30","author":"Morris","year":"2014","journal-title":"Bioinformatics"},{"key":"B44","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1056\/NEJMoa011858","article-title":"Exercise capacity and mortality among men referred for exercise testing","volume":"346","author":"Myers","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/sms.14241","article-title":"IL-6 signaling in acute exercise and chronic training: potential consequences for health and athletic performance","volume":"33","author":"Nash","year":"2023","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1249\/MSS.0000000000002970","article-title":"Epigenome-wide association study identified VTI1A DNA methylation associated with accelerometer-assessed physical activity","volume":"54","author":"Nishida","year":"2022","journal-title":"Med. Sci. Sports Exerc"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-9-r105","article-title":"Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia","volume":"14","author":"Nordlund","year":"2013","journal-title":"Genome Biol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1838162","DOI":"10.1155\/2018\/1838162","article-title":"Association of wrist circumference and waist-to-height ratio with cardiometabolic risk factors among type II diabetics in a Ghanaian population","volume":"2018","author":"Obirikorang","year":"2018","journal-title":"J. Diabetes Res."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1210\/jc.2011-2155","article-title":"Circulating levels of TNF-alpha are associated with impaired glucose tolerance, increased insulin resistance, and ethnicity: the Insulin Resistance Atherosclerosis Study","volume":"97","author":"Olson","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B50","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jneuroim.2007.01.003","article-title":"Role of glutamate on T-cell mediated immunity","volume":"185","author":"Pacheco","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/s41574-019-0174-x","article-title":"Physical activity and muscle-brain crosstalk","volume":"15","author":"Pedersen","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.1007\/s11357-024-01440-5","article-title":"Slowed epigenetic aging in Olympic champions compared to non-champions","volume":"47","author":"Radak","year":"2025","journal-title":"Geroscience"},{"key":"B53","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.freeradbiomed.2018.10.444","article-title":"Exercise effects on physiological function during aging","volume":"132","author":"Radak","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"B54","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1097\/JES.0b013e31823b5f13","article-title":"Skeletal muscle power: a critical determinant of physical functioning in older adults","volume":"40","author":"Reid","year":"2012","journal-title":"Exerc Sport Sci. Rev."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1210\/jc.2010-2432","article-title":"Contributions of cardiorespiratory fitness and visceral adiposity to six-year changes in cardiometabolic risk markers in apparently healthy men and women","volume":"96","author":"Rheaume","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B56","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s40279-020-01379-5","article-title":"Health consequences of an elite sporting career: long-term detriment or long-term gain? A meta-analysis of 165,000 former athletes","volume":"51","author":"Runacres","year":"2021","journal-title":"Sports Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1556\/2006.7.2018.35","article-title":"Expression of NMDA receptor subunits in human blood lymphocytes: a peripheral biomarker in online computer game addiction","volume":"7","author":"Sadat-Shirazi","year":"2018","journal-title":"J. Behav. Addict."},{"key":"B58","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13059-018-1448-7","article-title":"An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray","volume":"19","author":"Salas","year":"2018","journal-title":"Genome Biol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1152\/physiolgenomics.00117.2015","article-title":"Twin-sibling study and meta-analysis on the heritability of maximal oxygen consumption","volume":"48","author":"Schutte","year":"2016","journal-title":"Physiol. Genomics"},{"key":"B60","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1007\/s10522-019-09818-1","article-title":"Epigenome-wide exploratory study of monozygotic twins suggests differentially methylated regions to associate with hand grip strength","volume":"20","author":"Soerensen","year":"2019","journal-title":"Biogerontology"},{"key":"B61","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1123\/jpah.6.5.667","article-title":"The effect of habitual smoking on measured and predicted VO2(max)","volume":"6","author":"Suminski","year":"2009","journal-title":"J. Phys. Act. Health"},{"key":"B62","doi-asserted-by":"publisher","first-page":"10487","DOI":"10.1073\/pnas.1805668115","article-title":"Rapid stimulation of human dentate gyrus function with acute mild exercise","volume":"115","author":"Suwabe","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B63","doi-asserted-by":"publisher","first-page":"5140","DOI":"10.1038\/s41598-017-04850-y","article-title":"Aerobic fitness associates with mnemonic discrimination as a mediator of physical activity effects: evidence for memory flexibility in young adults","volume":"7","author":"Suwabe","year":"2017","journal-title":"Sci. Rep."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1016\/s0002-9149(02)02302-0","article-title":"Comparison of cardiorespiratory fitness versus leisure time physical activity as predictors of coronary events in men aged < or = 65 years and > 65 years","volume":"89","author":"Talbot","year":"2002","journal-title":"Am. J. Cardiol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/s0735-1097(00)01054-8","article-title":"Age-predicted maximal heart rate revisited","volume":"37","author":"Tanaka","year":"2001","journal-title":"J. Am. Coll. Cardiol."},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14101","article-title":"Alterations of the gut microbiome are associated with epigenetic age acceleration and physical fitness","volume":"23","author":"Torma","year":"2024","journal-title":"Aging Cell"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0210653","article-title":"A body-fixed-sensor-based analysis of stair ascent and sit-to-stand to detect age-related differences in leg-extensor power","volume":"14","author":"Van Roie","year":"2019","journal-title":"PloS One"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13859","article-title":"Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle","volume":"23","author":"Voisin","year":"2024","journal-title":"Aging Cell"},{"key":"B69","doi-asserted-by":"publisher","first-page":"8628","DOI":"10.1038\/sj.onc.1207232","article-title":"TRAIL and apoptosis induction by TNF-family death receptors","volume":"22","author":"Wang","year":"2003","journal-title":"Oncogene"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2020.111172","article-title":"Jump power, leg press power, leg strength and grip strength differentially associated with physical performance: The Developmental Epidemiologic Cohort Study (DECOS)","volume":"145","author":"Winger","year":"2021","journal-title":"Exp. Gerontol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"7982","DOI":"10.1038\/s41598-018-26210-0","article-title":"Exercise activates the PI3K-AKT signal pathway by decreasing the expression of 5alpha-reductase type 1 in PCOS rats","volume":"8","author":"Wu","year":"2018","journal-title":"Sci. Rep."},{"key":"B72","doi-asserted-by":"publisher","first-page":"551 e517","DOI":"10.1016\/j.jamda.2017.03.011","article-title":"Association of grip strength with risk of all-cause mortality, cardiovascular diseases, and cancer in community-dwelling populations: a meta-analysis of prospective cohort studies","volume":"18","author":"Wu","year":"2017","journal-title":"J. Am. Med. Dir. Assoc."},{"key":"B73","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41514-025-00217-0","article-title":"Relationship between physical activity and DNA methylation-predicted epigenetic clocks","volume":"11","author":"You","year":"2025","journal-title":"NPJ Aging"},{"key":"B74","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2015.1011888","article-title":"Involvement of USP24 in the DNA damage response","volume":"3","author":"Zhang","year":"2016","journal-title":"Mol. Cell. Oncol."},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw967","article-title":"Comprehensive characterization, annotation and innovative use of Infinium DNA methylation BeadChip probes","volume":"45","author":"Zhou","year":"2017","journal-title":"Nucleic Acids Res."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2026.1713760\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T12:02:11Z","timestamp":1776254531000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2026.1713760\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":76,"alternative-id":["10.3389\/fphys.2026.1713760"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2026.1713760","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]},"article-number":"1713760"}}