Satellite-cell pool size does matter: Defining the myogenic potency of aging skeletal muscle

Abstract

The deteriorating in vivo environment is thought to play a major role in reduced stem cell function with age. The capacity of stem cells to support tissue maintenance depends not only on their response to cues from the surrounding niche, but also on their abundance. Here, we investigate satellite cell (myogenic stem cell) pool size and its potential to participate in muscle maintenance through old age. The numbers and performance of mouse satellite cells have been analyzed using molecular markers that exclusively characterize quiescent satellite cells and their progeny as they transit through proliferation, differentiation and generation of reserve cells. The study establishes that abundance of resident satellite cells declines with age in myofibers from both fast- and slow-twitch muscles. Nevertheless, the inherent myogenic potential of satellite cells does not diminish with age. Furthermore, the aging satellite cell niche retains the capacity to support effective myogenesis upon enrichment of the mitogenic milieu with FGF. Altogether, satellite cell abundance, but not myogenic potential, deteriorates with age. This study suggests that the population of satellite cells that participate in myofiber maintenance during routine muscle utilization is not fully replenished throughout life.

Human muscle satellite cells show age-related differential expression of S100B protein and RAGE

“…This conclusion was supported by the finding that adding the mitogenic S100B to aged SCs in GM followed by cultivation in DM without additions resulted in a significant stimulation of MyHC expression and myotube formation (Fig. 8f) similar to what was described using bFGF (Shefer et al 2006). …”

Losing stem cells in the aged skeletal muscle niche

“…First, the authors confirmed previous studies showing that satellite cell numbers decline with age [8,9]. It is notable that the extent of decline was variable in previous studies, as well as in the present report, likely due to the methods and markers employed (on muscle sections or isolated myofibers), muscle group examined, or other factors such as genetic strain of mice.…”

In vivo GDF3 administration abrogates aging related muscle regeneration delay following acute sterile injury

“…The ability of satellite cells to repair injured muscle markedly declines with aging (Cheung & Rando, 2013). Aside from reduced numbers of satellite cells (Garcia‐Prat, Sousa‐Victor, & Munoz‐Canoves, 2013; Shefer, Mark, Richardson, & Yablonka‐Reuveni, 2006), the differentiation capacity of satellite cells is also reduced with aging. Moreover, the number of differentiating satellite cells is decreased in aged mice, as shown by downregulation of differentiation markers such as desmin and myogenin (Charge, Brack, & Hughes, 2002; Collins, Zammit, Ruiz, Morgan, & Partridge, 2007).…”