Delayed molecular aging, preservation of energy metabolism and enhanced exercise response in exercise-trained human muscle.

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

Laboratory Genetic Metabolic Diseases, University of Amsterdam, Amsterdam, the Netherlands. [email protected] Genetic Metabolic Diseases, University of Amsterdam, Amsterdam, the Netherlands. [email protected]. · pubmed

Paper

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

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Research summary

Exercise training preserves youthful molecular profiles in skeletal muscle and enhances acute exercise responses in older adults, suggesting a mechanism for mitigating age-related metabolic decline. This study provides solid observational evidence linking physical fitness to the preservation of mitochondrial and metabolic function, which is a fundamental pillar of healthy aging, though it does not propose a novel therapeutic intervention or solve a root cause of aging directly.

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