Muscle memory and a new cellular model for muscle atrophy and hypertrophy

Abstract

Memory is a process in which information is encoded, stored, and retrieved. For vertebrates, the modern view has been that it occurs only in the brain. This review describes a cellular memory in skeletal muscle in which hypertrophy is 'remembered' such that a fibre that has previously been large, but subsequently lost its mass, can regain mass faster than naive fibres. A new cell biological model based on the literature, with the most reliable methods for identifying myonuclei, can explain this phenomenon. According to this model, previously untrained fibres recruit myonuclei from activated satellite cells before hypertrophic growth. Even if subsequently subjected to grave atrophy, the higher number of myonuclei is retained, and the myonuclei seem to be protected against the elevated apoptotic activity observed in atrophying muscle tissue. Fibres that have acquired a higher number of myonuclei grow faster when subjected to overload exercise, thus the nuclei represent a functionally important 'memory' of previous strength. This memory might be very long lasting in humans, as myonuclei are stable for at least 15 years and might even be permanent. However, myonuclei are harder to recruit in the elderly, and if the long-lasting muscle memory also exists in humans, one should consider early strength training as a public health advice. In addition, myonuclei are recruited during steroid use and encode a muscle memory, at least in rodents. Thus, extending the exclusion time for doping offenders should be considered.

Satellite cell depletion prevents fiber hypertrophy in skeletal muscle

“…The relevant bottleneck relating the number of nuclei to cytoplasmic volume is not known, although it has been speculated that capacity for shuttling of macromolecules over the nuclear membrane could act as a limiting factor if the number of nuclei is not sufficiently high (Gundersen, 2016;Hall et al, 2011).…”

“…The demonstration of the muscle memory phenomenon Bruusgaard et al, 2010;Egner et al, 2013; for a review, see Gundersen, 2016), for which efficient re-growth relies on myonuclei recruited during a previous hypertrophic episode, is an important example of functional radial growth without the need for new myonuclei from satellite cells. This has been directly demonstrated using the hind limb suspension model, in which atrophy is induced by lifting up the hind part of rodents by the tail and thereby unloading the hind leg.…”

Prevention of muscle wasting and osteoporosis: the value of examining novel animal models

“…However, apoptosis as a mechanism for causing myonuclear loss during muscle atrophy is highly controversial, as recent studies using in vivo time-lapse imaging found that the number of myonuclei remained relatively constant during both tenotomy (see Glossary) and detraining (Gundersen, 2016). Whereas in vivo imaging allows direct examination of myonuclei, many studies have reported markers for apoptosis in homogenates derived from atrophying muscle and have interpreted this as apoptosis of myonuclei, but these findings could reflect apoptosis of nuclei from other cell types, such as stromal cells or satellite cells (Gundersen, 2016).…”

“…Whereas in vivo imaging allows direct examination of myonuclei, many studies have reported markers for apoptosis in homogenates derived from atrophying muscle and have interpreted this as apoptosis of myonuclei, but these findings could reflect apoptosis of nuclei from other cell types, such as stromal cells or satellite cells (Gundersen, 2016). Indeed, a recent study found that although the amount of Bax mRNA and the number of TUNEL-positive nuclei were significantly increased in immobilised human muscle, this was mainly localised in the interstitial space between myocytes, thus potentially being attributable to other cell types (Suetta et al, 2012).…”

Skeletal Muscles Do not Undergo Apoptosis During Either Atrophy or Programmed Cell Death

“…The plastic nature of muscle, and its syncytial status, has given rise to a controversy in the field that only recently appears to have been resolved-the "myonuclear domain hypothesis" [7][8][9]. This theory has its origins in the concept of "Wirkungssphäre, " or "sphere of influence," proposed by Strassburger in 1893 [10], in which he argued that a nucleus can only support a descrete volume of cytoplasm, which in turn defines the upper limits to cell size.…”