Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle
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Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late- life exercise mitigates epi -genetic 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 aero -bic 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 struc-ture, 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.
Original language | English |
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Article number | e13859 |
Journal | Aging Cell |
Volume | 23 |
Issue number | 1 |
Number of pages | 15 |
ISSN | 1474-9718 |
DOIs | |
Publication status | Published - 2024 |
Bibliographical note
Publisher Copyright:
© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
- aging, cardiorespiratory fitness, DNA methylation, exercise training, human skeletal muscle, meta-analysis, mRNA expression
Research areas
ID: 347485717