TY - JOUR
T1 - Late-life exercise mitigates skeletal muscle epigenetic aging
AU - Murach, Kevin A.
AU - Dimet-Wiley, Andrea L.
AU - Wen, Yuan
AU - Brightwell, Camille R.
AU - Latham, Christine M.
AU - Dungan, Cory M.
AU - Fry, Christopher
AU - Watowich, Stanley J.
N1 - Publisher Copyright:
© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
PY - 2022/1
Y1 - 2022/1
N2 - There are functional benefits to exercise in muscle, even when performed late in life, but the contributions of epigenetic factors to late-life exercise adaptation are poorly defined. Using reduced representation bisulfite sequencing (RRBS), ribosomal DNA (rDNA) and mitochondrial-specific examination of methylation, targeted high-resolution methylation analysis, and DNAge™ epigenetic aging clock analysis with a translatable model of voluntary murine endurance/resistance exercise training (progressive weighted wheel running, PoWeR), we provide evidence that exercise may mitigate epigenetic aging in skeletal muscle. Late-life PoWeR from 22–24 months of age modestly but significantly attenuates an age-associated shift toward promoter hypermethylation. The epigenetic age of muscle from old mice that PoWeR-trained for eight weeks was approximately eight weeks younger than 24-month-old sedentary counterparts, which represents ~8% of the expected murine lifespan. These data provide a molecular basis for exercise as a therapy to attenuate skeletal muscle aging.
AB - There are functional benefits to exercise in muscle, even when performed late in life, but the contributions of epigenetic factors to late-life exercise adaptation are poorly defined. Using reduced representation bisulfite sequencing (RRBS), ribosomal DNA (rDNA) and mitochondrial-specific examination of methylation, targeted high-resolution methylation analysis, and DNAge™ epigenetic aging clock analysis with a translatable model of voluntary murine endurance/resistance exercise training (progressive weighted wheel running, PoWeR), we provide evidence that exercise may mitigate epigenetic aging in skeletal muscle. Late-life PoWeR from 22–24 months of age modestly but significantly attenuates an age-associated shift toward promoter hypermethylation. The epigenetic age of muscle from old mice that PoWeR-trained for eight weeks was approximately eight weeks younger than 24-month-old sedentary counterparts, which represents ~8% of the expected murine lifespan. These data provide a molecular basis for exercise as a therapy to attenuate skeletal muscle aging.
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U2 - 10.1111/acel.13527
DO - 10.1111/acel.13527
M3 - Article
C2 - 34932867
AN - SCOPUS:85121483182
SN - 1474-9718
VL - 21
JO - Aging cell
JF - Aging cell
IS - 1
M1 - e13527
ER -