Myonuclear permanence in skeletal muscle memory: a systematic review and meta‐analysis of human and animal studies

Abstract

One aspect of skeletal muscle memory is the ability of a previously trained muscle to hypertrophy more rapidly following a period of detraining. Although the molecular basis of muscle memory remains to be fully elucidated, one potential mechanism thought to mediate muscle memory is the permanent retention of myonuclei acquired during the initial phase of hypertrophic growth. However, myonuclear permanence is debated and would benefit from a meta-analysis to clarify the current state of the field for this important aspect of skeletal muscle plasticity. The objective of this study was to perform a meta-analysis to assess the permanence of myonuclei associated with changes in physical activity and ageing. When available, the abundance of satellite cells (SCs) was also considered given their potential influence on changes in myonuclear abundance. One hundred forty-seven peer-reviewed articles were identified for inclusion across five separate meta-analyses; (1-2) human and rodent studies assessed muscle response to hypertrophy; (3-4) human and rodent studies assessed muscle response to atrophy; and (5) human studies assessed muscle response with ageing. Skeletal muscle hypertrophy was associated with higher myonuclear content that was retained in rodents, but not humans, with atrophy (SMD = À0.60, 95% CI À1.71 to 0.51, P = 0.29, and MD = 83.46, 95% CI À649.41 to 816.32, P = 0.82; respectively). Myonuclear and SC content were both lower following atrophy in humans (MD = À11, 95% CI À0.19 to À0.03, P = 0.005, and SMD = À0.49, 95% CI À0.77 to À0.22, P = 0.0005; respectively), although the response in rodents was affected by the type of muscle under consideration and the mode of atrophy. Whereas rodent myonuclei were found to be more permanent regardless of the mode of atrophy, atrophy of ≥30% was associated with a reduction in myonuclear content (SMD = À1.02, 95% CI À1.53 to À0.51, P = 0.0001). In humans, sarcopenia was accompanied by a lower myonuclear and SC content (MD = 0.47, 95% CI 0.09 to 0.85, P = 0.02, and SMD = 0.78, 95% CI 0.37-1.19, P = 0.0002; respectively). The major finding from the present meta-analysis is that myonuclei are not permanent but are lost during periods of atrophy and with ageing. These findings do not support the concept of skeletal muscle memory based on the permanence of myonuclei and suggest other mechanisms, such as epigenetics, may have a more important role in mediating this aspect of skeletal muscle plasticity.

New Findings: Hindlimb Unloading Causes Nucleocytoplasmic Ca2+ Overload and DNA Damage in Skeletal Muscle

“…While some studies reported that myonuclei were eliminated [ 50 , 51 ], others suggested they were not lost [ 52 , 53 ]. Some studies have pointed out that the discrepancies may be attributed to multiple factors, such as variations in experimental models, limited number of studies, and differences in research design [ 54 ]. It is important to note that the maintenance of quantity of myonuclei requires a balance between their production and apoptosis.…”

Short- and long-term outcomes of laparoscopic vs open surgery for T2 gallbladder cancer: A systematic review and meta-analysis

“…The quality of the cohort studies (retrospective or prospective) was assessed using the Newcastle-Ottawa Scale, which specifically included study population selection, comparability, and exposure evaluation or outcome evaluation. The RCTs were conducted for the risk assessment according to the “risk assessment tool” recommended by the Cochrane Collaboration Network[ 18 - 20 ].…”

Implications of gender-affirming endocrine care for sports participation

“… 81 In humans, a 1999 study compared the muscle physiology of powerlifters who were users ( n = 9) and non-users of high-dose steroids ( n = 10) and found that the number of myonuclei and the proportion of myonuclei were significantly higher in the steroid users. 80 However, the concept of muscle memory has mainly been based on animal models, with a recent comprehensive review 82 and systematic review and meta-analysis 83 finding no clear evidence for the existence of muscle memory by myonuclei retention in both animal and human studies. In particular, it appears that ‘muscle memory’ is a phenomenon that is not observed in many studies or not retained long term, with many studies, 82 , 83 and it could be debated that any memory marks altered during previous training would be easily modified or overridden by changes in sex hormone concentrations and the subsequent systematic effects of GAHT.…”

“… 80 However, the concept of muscle memory has mainly been based on animal models, with a recent comprehensive review 82 and systematic review and meta-analysis 83 finding no clear evidence for the existence of muscle memory by myonuclei retention in both animal and human studies. In particular, it appears that ‘muscle memory’ is a phenomenon that is not observed in many studies or not retained long term, with many studies, 82 , 83 and it could be debated that any memory marks altered during previous training would be easily modified or overridden by changes in sex hormone concentrations and the subsequent systematic effects of GAHT. Further research exploring physiological and epigenetic changes in trans men and women using GAHT could provide great molecular insights into the performance differences between cis and trans populations and is an area of future need.…”