Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle

Voisin, Sarah ORCID: 0000-0002-4074-7083, Seale, Kristen, Jacques, Macsue ORCID: 0000-0002-4337-7022, Landen, Shanie ORCID: 0000-0002-7658-030X, Harvey, Nicholas ORCID: 0000-0003-2035-8475, Haupt, Larisa M ORCID: 0000-0002-7735-8110, Griffiths, Lyn R ORCID: 0000-0002-6774-5475, Ashton, Kevin J ORCID: 0000-0001-6106-3425, Coffey, Vernon G, Thompson, Jamie-Lee M, Doering, Thomas M, Lindholm, Malene E, Walsh, Colum, Davison, Gareth, Irwin, Rachelle, McBride, Catherine, Hansson, Ola, Asplund, Olof, Heikkinen, Aino E, Piirilä, Päivi, Pietiläinen, Krisi H., Ollikainen, Miina, Blocquiaux, Sara, Thomis, Martine, Coletta, Dawn K, Sharples, Adam P and Eynon, Nir ORCID: 0000-0003-4046-8276 (2024) Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle. Aging Cell, 23 (1). ISSN 1474-9718


Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, (2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns toward a younger profile, and (3) muscle disuse “ages” the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted toward a younger state after exercise training interventions, while the transcriptome shifted toward an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism, and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.

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Item type Article
URI https://vuir.vu.edu.au/id/eprint/48038
DOI 10.1111/acel.13859
Official URL http://dx.doi.org/10.1111/acel.13859
Funders http://purl.org/au-research/grants/nhmrc/1140644, http://purl.org/au-research/grants/nhmrc/11577321
Subjects Current > FOR (2020) Classification > 4207 Sports science and exercise
Current > Division/Research > Institute for Health and Sport
Keywords exercise training, age-related transcripts, DNA methylation loci, methylome and transcriptome profiles, genes, muscle structure, metabolism, mitochondrial function
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