Abstract
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.
Highlights
All tissues, including skeletal muscle, undergo DNA methylation alterations across the lifespan (Turner et al, 2020; Sailani et al, 2019) that may contribute to structural and functional decline with aging
Using reduced representation bisulfite sequencing (RRBS), ribosomal DNA and mitochondrial-specific examination of methylation, targeted high- resolution methylation analysis, and DNAgeTM epigenetic aging clock analysis with a translatable model of voluntary murine endurance/resistance exercise training, we provide evidence that exercise may mitigate epigenetic aging in skeletal muscle
Using the high-volume resistance/endurance exercise of progressive weighted wheel running (PoWeR) developed by our laboratory (Murach et al, 2020), mice were trained from 22–24 months of age
Summary
All tissues, including skeletal muscle, undergo DNA methylation alterations across the lifespan (Turner et al, 2020; Sailani et al, 2019) that may contribute to structural and functional decline with aging. 68 CpG sites that mapped to at least one of 27 genes were hypomethylated (Table S2a), while 864 distinct CpG sites that mapped to one or more of 146 genes were hypermethylated in aged sedentary muscle relative to young (Table S2b, FDR
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