Myonuclear permanence in skeletal muscle memory: a systematic review and meta-analysis of human and animal studies.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of human and animal studies (graded by design analogy for biological science)
PubMed 35961635 · doi:10.1002/jcsm.13043
What was done
The authors conducted a systematic review and meta-analysis across 147 peer-reviewed articles to assess the permanence of skeletal muscle myonuclei during physical activity changes and ageing. When available, satellite cell (SC) abundance was also evaluated. Five separate meta-analyses were performed: (1–2) human and rodent muscle response to hypertrophy, (3–4) human and rodent muscle response to atrophy, and (5) human muscle response to ageing.
What was found
Hypertrophy increased myonuclear content across humans and rodents. Following muscle atrophy, myonuclear content was retained in rodents overall (SMD = -0.60, 95% CI -1.71 to 0.51, P = 0.29) but not in humans (MD = 83.46, 95% CI -649.41 to 816.32, P = 0.82 for retention models). In humans, atrophy significantly decreased both myonuclear content (MD = -11, 95% CI -0.19 to -0.03, P = 0.005) and SC content (SMD = -0.49, 95% CI -0.77 to -0.22, P = 0.0005). Rodents showed significant myonuclear loss when atrophy reached or exceeded 30% (SMD = -1.02, 95% CI -1.53 to -0.51, P = 0.0001). Sarcopenia in humans was also accompanied by lower myonuclear content (MD = 0.47, 95% CI 0.09 to 0.85, P = 0.02) and SC content (SMD = 0.78, 95% CI 0.37 to 1.19, P = 0.0002).
Why it matters
This review challenges the prevailing hypothesis that skeletal muscle memory is driven by permanent myonuclear accretion from prior training. The findings suggest that enhanced muscle regrowth during retraining is mediated by other mechanisms, such as epigenetic alterations, rather than static myonuclear retention.
Limits
The included studies pooled heterogeneous human and rodent models with varied modes of atrophy (e.g., disuse versus denervation) and different muscle types. Several human estimates had wide confidence intervals reflecting small sample sizes and variability in muscle biopsy quantification techniques.
Cited by
- contradicts Muscle memory is mediated in part by myonuclei donated from satellite cells that fuse into muscle fibers and remain permanently.