Fight Aging!

While it may or may not turn out to hold true for every stem cell population in the body, there is a fair amount of evidence for muscle stem cells to remain competent and in principle capable of maintaining tissue well into later life. The loss of function that we observe in muscle tissue in old age is much more a matter of inactivity rather than incapacity. This inactivity may be an evolved response to a damaged environment, lowering cancer risk at the expense of a slow decline into frailty, or it may be the consequence of age-related molecular damage rising to pathological levels in the stem cell niche tissue, or both. That stem cells remain capable in old tissue suggests a shorter path to useful regenerative therapies - building treatments that work by rousing existing cells to action, rather than having to deliver new cells.

Age-related loss of muscle mass and strength is widely attributed to limitation in the capacity of muscle resident satellite cells to perform their myogenic function. This idea contains two notions that have not been comprehensively evaluated by experiment. First, it entails the idea that we damage and lose substantial amounts of muscle in the course of our normal daily activities. Second, it suggests that mechanisms of muscle repair are in some way exhausted, thus limiting muscle regeneration. A third potential option is that the aged environment becomes inimical to the conduct of muscle regeneration.

In the present study, we used our established model of human muscle xenografting to test whether muscle samples taken from cadavers, of a range of ages, maintained their myogenic potential after being transplanted into immunodeficient mice. We find no measurable difference in regeneration across the range of ages investigated up to 78 years of age. Moreover, we report that satellite cells maintained their myogenic capacity even when muscles were grafted 11 days postmortem in our model. We conclude that the loss of muscle mass with increasing age is not attributable to any intrinsic loss of myogenicity and is most likely a reflection of progressive and detrimental changes in the muscle microenvironment such as to disfavor the myogenic function of these cells.

Link: https://doi.org/10.1111/acel.13411