Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle
(2023) In Aging Cell p.1-15- Abstract
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... (More)
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.
(Less)
- author
- Voisin, Sarah
; Seale, Kirsten
; Jacques, Macsue
; Landen, Shanie
; Harvey, Nicholas R
; Haupt, Larisa M
; Griffiths, Lyn R
; Ashton, Kevin J
; Coffey, Vernon G
; Thompson, Jamie-Lee M
; Doering, Thomas M
; Lindholm, Malene E
; Walsh, Colum
; Davison, Gareth
; Irwin, Rachelle
; McBride, Catherine
; Hansson, Ola
LU
; Asplund, Olof
LU
; Heikkinen, Aino E
; Piirilä, Päivi
; Pietiläinen, Kirsi H
; Ollikainen, Miina
; Blocquiaux, Sara
; Thomis, Martine
; Dawn, Coletta K
; Sharples, Adam P
and Eynon, Nir
(Less) - organization
- publishing date
- 2023-05-02
- type
- Contribution to journal
- publication status
- epub
- subject
- in
- Aging Cell
- article number
- e13859
- pages
- 1 - 15
- publisher
- Wiley-Blackwell
- external identifiers
-
- pmid:37128843
- scopus:85157977495
- ISSN
- 1474-9726
- DOI
- 10.1111/acel.13859
- language
- English
- LU publication?
- yes
- additional info
- © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
- id
- 33b591ae-32a3-4b86-8cbc-1d098a38c896
- date added to LUP
- 2023-05-05 08:30:26
- date last changed
- 2023-12-07 03:00:35
@article{33b591ae-32a3-4b86-8cbc-1d098a38c896,
abstract = {{<p>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.</p>}},
author = {{Voisin, Sarah and Seale, Kirsten and Jacques, Macsue and Landen, Shanie and Harvey, Nicholas R and Haupt, Larisa M and Griffiths, Lyn R and Ashton, Kevin J and Coffey, Vernon G and Thompson, Jamie-Lee M and Doering, Thomas M and Lindholm, Malene E and Walsh, Colum and Davison, Gareth and Irwin, Rachelle and McBride, Catherine and Hansson, Ola and Asplund, Olof and Heikkinen, Aino E and Piirilä, Päivi and Pietiläinen, Kirsi H and Ollikainen, Miina and Blocquiaux, Sara and Thomis, Martine and Dawn, Coletta K and Sharples, Adam P and Eynon, Nir}},
issn = {{1474-9726}},
language = {{eng}},
month = {{05}},
pages = {{1--15}},
publisher = {{Wiley-Blackwell}},
series = {{Aging Cell}},
title = {{Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle}},
url = {{http://dx.doi.org/10.1111/acel.13859}},
doi = {{10.1111/acel.13859}},
year = {{2023}},
}