Seaborne · Scientific reports 2018 · prospective repeated-measures cohort study · n=?

Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy.

Cited 342 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective within-subject repeated-measures intervention study without a separate control group

PubMed 29382913 · doi:10.1038/s41598-018-20287-3 · record verified 2026-08-26

What was done

Genome-wide DNA methylation (850,000 CpG sites) and gene expression analyses were conducted in human skeletal muscle across three phases: hypertrophy induced by resistance loading, return of muscle mass to baseline during unloading, and subsequent hypertrophy following reloading. Epigenetic responses following a single acute exercise bout were also tracked.

What was found

Reloading produced a higher frequency of genome-wide hypomethylation (18,816 CpG sites) compared with initial loading (9,153 CpG sites). Specific genes (AXIN1, GRIK2, CAMK4, TRAF1) demonstrated hypomethylation and enhanced expression after loading that persisted through unloading when muscle mass returned to baseline. Another subset (UBR5, RPL35a, HEG1, PLA2G16, SETD3) showed hypomethylation and enhanced expression after loading, with the largest increases in hypomethylation, expression, and muscle mass occurring after reloading. Additionally, GRIK2, TRAF1, BICC1, and STAG1 were hypomethylated after a single exercise bout and retained this state 22 weeks later.

Why it matters

This study provides evidence that human skeletal muscle possesses an epigenetic memory of prior growth through enduring DNA hypomethylation, identifying candidate genes involved in muscle memory and adaptation to retraining.

Limits

The abstract does not state the sample size, participant demographics, baseline training status, or the precise magnitude of muscle mass changes. There is no separate untrained control group reported in the abstract.

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