{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:00:42Z","timestamp":1780981242223,"version":"3.54.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"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":"\n Background<\/jats:title>\n Intrinsic exercise capacity is a strong predictor of health and longevity and is independently associated with aging- and disease-related outcomes. Although previous studies using low- and high-capacity runner (LCR and HCR) rats have demonstrated organ-specific patterns of epigenetic aging, the molecular mechanisms linking intrinsic aerobic capacity to skeletal muscle signaling remain incompletely understood.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n This study investigated whether intrinsic exercise capacity is associated with alterations in skeletal muscle clock gene expression and insulin-like growth factor-1 (IGF-1)\u2013related signaling pathways.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Female LCR and HCR rats (23\u201324 months old, 44th generation) underwent maximal oxygen uptake (VO\n 2<\/jats:sub>\n max) testing, followed by molecular analyses of plantaris and soleus muscles using quantitative PCR and Western blotting.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n VO\n 2<\/jats:sub>\n max was significantly higher in HCR rats. In skeletal muscle, LCR rats exhibited higher mRNA expression levels of Cry1, Bmal1, Igf1, and Igf1Ec measured at ZT2\u2013ZT3, whereas expression of Cry2, Pdk4, and MuRF-1 did not differ between phenotypes. Despite increased\n Igf1<\/jats:italic>\n expression in LCR rats, the phosphorylated-to-total JAK2 ratio was reduced, while STAT5 phosphorylation was unchanged. Correlation analyses demonstrated significant negative associations between VO\n 2<\/jats:sub>\n max and\n Igf1<\/jats:italic>\n ,\n Igf1Ec<\/jats:italic>\n ,\n Cry1<\/jats:italic>\n , and\n Bmal1<\/jats:italic>\n expression.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n These findings indicate that low intrinsic exercise capacity is associated with coordinated alterations in skeletal muscle clock gene expression and IGF-1\u2013 related signaling, suggesting altered IGF-1\u2013related signaling balance in aging skeletal muscle. These results provide mechanistic insight into how intrinsic aerobic capacity may influence muscle biology and health trajectories during aging.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fphys.2026.1818866","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T04:28:45Z","timestamp":1780979325000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intrinsic exercise capacity is associated with skeletal muscle clock gene and IGF-1 signaling in aged low- and high-running capacity rats"],"prefix":"10.3389","volume":"17","author":[{"given":"Hyeon-Ki","family":"Kim","sequence":"first","affiliation":[{"name":"Research Center for Molecular Exercise Science, Hungarian University of Sport Science","place":["Budapest, Hungary"]},{"name":"Medicine and Science in Sports and Exercise, Graduate School of Medicine, Tohoku University","place":["Sendai, Japan"]},{"name":"Center for Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition","place":["Osaka, Japan"]},{"name":"Department of Public Health and Health Policy, Graduate School of Biomedical and Health Sciences, Hiroshima University","place":["Hiroshima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuji","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Exercise Science, Hungarian University of Sport Science","place":["Budapest, Hungary"]},{"name":"Smart-Aging Research Center, Tohoku University","place":["Sendai, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Bori","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Exercise Science, Hungarian University of Sport Science","place":["Budapest, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren Gerard","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences","place":["Toledo, OH, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven Loyal","family":"Britton","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, University of Michigan","place":["Ann Arbor, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Radak","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Exercise Science, Hungarian University of Sport Science","place":["Budapest, Hungary"]},{"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":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081773","article-title":"Implications of insulin-like growth factor-1 in skeletal muscle and various diseases","volume":"9","author":"Ahmad","year":"2020","journal-title":"Cells"},{"key":"B2","doi-asserted-by":"publisher","first-page":"19090","DOI":"10.1073\/pnas.1014523107","article-title":"CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function","volume":"107","author":"Andrews","year":"2010","journal-title":"Proc. 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