Muscle memory: virtues of your youth?

Traditionally the term “muscle memory” has often, but misleadingly, been used synonymously with motor learning in the CNS, such as when one can ride a bike even after many years without biking. More recently a cellular memory residing in the muscle cells themselves was demonstrated related to regulation of muscle mass (Bruusgaard et al. 2010; Egner et al. 2013). The data suggested that previous strength might aid new training even long after the muscle mass was lost. The memory effect was demonstrated with the use of steroids and overload hypertrophy obtained by synergist ablation, and evidence that physiologically relevant exercise induces a memory has been scarce.

In this issue of The Journal of Physiology Lee et al. (2018) subjected rats to weight‐loaded ladder training for 8 weeks. This led to a 9% increase in fibre size. The animals then stopped training for 20 weeks, after which the fibre size essentially returned to pre‐training levels. When the pre‐trained animals were subjected to 8 weeks of re‐training the growth was stronger, i.e. 15%. Although not all changes were statistically significant, the observations on muscle mass as a proxy for hypertrophy were statistically clearer.

Importantly Lee et al. (2018) report that the number of myonuclei is increased by the strength exercise, and that these “extra” nuclei are not lost during the subsequent de‐training atrophy. This goes to the foundation of the muscle memory hypothesis.

Older literature based on conventional histology concluded that myonuclei are lost by apoptosis during atrophy, but this has been refuted by direct observation using time‐lapse, in vivo, imaging (Bruusgaard & Gundersen, 2008; Bruusgaard et al. 2010), and observations on isolated fibres: there is no loss of myonuclei during atrophy.

Lee et al. (2018) observed a 23% increase in the number of myonuclei during the first training session and this number was in principle constant during subsequent de‐training and re‐training. Thus, although the re‐training started with muscle fibres of the same size they contained a significantly higher number of myonuclei.

Each myonucleus is surrounded by a synthetic machinery which seems to be localized (Pavlath et al. 1989), and it has been argued since the 19th century that each nucleus can serve only a certain cytoplasmic volume.

A memory based on an elevated number of myonuclei could be very long lasting since muscle is a permanent tissue. In humans, the turnover of cells has been studied by utilizing the peak in ¹⁴C availability after atmospheric post‐war testing of nuclear bombs. For skeletal muscle, the half‐life was estimated to be 15 years (Spalding et al. 2005). This is probably a low estimate since >40% of the nuclei in the tissue are found in other cells less permanent than the myofibres (Winje et al. 2018).

With such longevity, the finding that a muscle memory can be induced by exercise might have important implications for healthy ageing. Generation of new myonuclei from satellite cells seems to be required for a “first time” hypertrophy, but not for regrowth. Importantly, the ability to generate new myonuclei is impaired in the elderly. The impairment is explained by cell‐intrinsic dysfunction of signalling pathways in the aged satellite cells, and dysregulation of cell‐extrinsic signals, both blood borne and locally from the myofibre (Blau et al. 2015). The existence of a muscle memory opens up the possibility that myonuclei should be acquired when young, to be of benefit when getting old.

The memory residing in the muscle cells has all the classical characteristics of “memory” with encoding, storage and retrieval (Fig. 1). It can be encoded by de novo exercise, stored as an increased number of nuclei and retrieved by new training.

Figure 1.

Schematic illustration of a muscle memory demonstrating the encoding, storage and retrieval of “information” related to strength exercise

The muscle memory hypothesis was recently supported by a human exercise study (Seaborne et al. 2018). In this study the number of myonuclei was not recorded, but an effect on DNA methylation was observed, leading the authors to suggest that the memory was related to epigenetic alterations. Although the functional importance of this mechanism is still not clear, future research on muscle memory should take into consideration both the number of nuclei and epigenetic alterations that might influence the capacity of each nucleus to produce protein.

Additional information

Competing interests

None declared.

Author contributions

All authors have approved the final version of the manuscript and agree to be accountable for all aspects of the work. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed.

Funding

I.M.E., E.E. and M.B. are supported by grant 240374 from the Norwegian Research Council.