Authors
Georges E Janssens, Maria M Trętowicz, Lotte Grevendonk, Marit Kotte, Angelique Scantlebery, Bauke V Schomakers, Michel van Weeghel, Jill Hermans, Martin A T Vervaart, Eric J M Wever, Simone W Denis, Aldo Jongejan, Gajja S Salomons, Frédéric M Vaz, Patrick Schrauwen, Joris Hoeks, Riekelt H Houtkooper
Published in
Nature aging. Jul 03, 2026. Epub Jul 03, 2026.
Abstract
Exercise is fundamental to healthy aging, yet how it mitigates age-related molecular changes and how fitness level shapes exercise responses remain unclear. To address these questions, we performed transcriptomics, lipidomics and metabolomics on skeletal muscle of young and older adults with differing physical function, both before and after an acute bout of submaximal exercise. At baseline, older adults exhibited reduced expression of genes associated with cellular respiration and energy metabolism compared to young adults with comparable activity levels. Here we found that 50% of these age-related differences were absent in trained older adults, resulting in profiles resembling those of young adults. Although all participants displayed transcriptional immune and stress responses upon acute exercise, the magnitude of these responses in older adults was positively correlated with their physical fitness. Integrated multiomic analyses further revealed links among mitochondrial respiration, lipid metabolism, stress responses and NAD+ biology. These findings demonstrate that sustained physical training transforms age-related molecular profiles and provide a molecular atlas for study of fitness-dependent aging mechanisms.
PMID:
42399371
Bibliographic data and abstract were imported from PubMed on 04 Jul 2026.
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