Nucleus Type-Specific DNA Methylomics Reveals Epigenetic "Memory" of Prior Adaptation in Skeletal Muscle.
Level 5 - mechanism / opinion, no new human data
Animal research with no human clinical data
PubMed 34870208 · doi:10.1093/function/zqab038
What was done
Adult (>4 months old) HSA-GFP mice underwent 8 weeks of progressive weighted wheel running (PoWeR), followed by 12 weeks of detraining, and were compared with age-matched untrained controls. Myonuclei and interstitial nuclei were isolated from plantaris muscles using fluorescent sorting. DNA methylation was assessed via reduced representation bisulfite sequencing (RRBS), and tissue gene expression was evaluated with RNA sequencing. A subset of mice underwent 4 weeks of retraining to compare whole-muscle and fiber type-specific growth against training-naive controls.
What was found
Training altered promoter methylation in both nuclear populations: myonuclei showed balanced hypo- and hyper-methylation, whereas interstitial nuclei exhibited substantial promoter hypomethylation. Reciprocal regulation was observed in specific pathways, such as promoter hypomethylation of Wnt signaling genes in myonuclei alongside hypermethylation in interstitial nuclei. Following 12 weeks of detraining, differential promoter methylation persisted in both nucleus types despite RNA-sequencing showing no enduring changes in bulk muscle gene expression. Upon 4 weeks of retraining, previously trained mice showed greater whole-muscle and fiber type-specific hypertrophy than naive mice, without differences in myonuclear number. The abstract reports durations and qualitative directional changes but provides no specific quantitative effect sizes or p-values.
Why it matters
This study provides evidence that skeletal muscle retains an epigenetic memory of prior training stored as DNA methylation marks in distinct nuclear populations, facilitating enhanced adaptation to retraining independent of myonuclear addition.
Limits
The study was conducted exclusively in a specific mouse running model, and translatability to human resistance or endurance exercise is unproven. The abstract does not report the total sample size (n), quantitative effect sizes, variance, or statistical thresholds. Bulk RNA sequencing was performed rather than single-nucleus transcriptomics.
Cited by
- supports Muscle memory involves an epigenetic component.