Functional dysregulation of stem cells during aging: a focus on skeletal muscle stem cells

Abstract

Aging of an organism is associated with the functional decline of tissues and organs, as well as a sharp decline in the regenerative capacity of stem cells. A prevailing view holds that the aging rate of an individual depends on the ratio of tissue attrition to tissue regeneration. Therefore, manipulations that favor the balance towards regeneration may prevent or delay aging. Skeletal muscle is a specialized tissue composed of postmitotic myofibers that contract to generate force. Satellite cells are the adult stem cells responsible for skeletal muscle regeneration. Recent studies on the biology of skeletal muscle and satellite cells in aging have uncovered the critical impact of systemic and niche factors on stem cell functionality and demonstrated the capacity of aged satellite cells to rejuvenate and increase their regenerative potential when exposed to a youthful environment. Here we review the current literature on the coordinated relationship between cell extrinsic and intrinsic factors that regulate the function of satellite cells, and ultimately determine tissue homeostasis and repair during aging, and which encourage the search for new anti‐aging strategies.

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).…”

Autophagy and genomic integrity

“…109 Moreover, autophagy also has a role in stem cells maintenance, 110 suggesting that this pathway may also fight accelerated aging by maintaining the health of the stem cell population, avoiding loss of regenerative potential. 111 Accumulation of oxidatively generated damage has been implicated in several neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. 112,113 Data point to autophagy as an important factor in the context of both the pathogenesis and, consequently, therapy of these pathologies.…”

Role of satellite cells in skeletal muscle plasticity: Beyond muscle regeneration

“…During sarcopenia, loss of skeletal muscle mass is caused by both a loss of myofibers and a decrease in myofiber cross-sectional area 20,21) . Because myonuclei are post-mitotic, and only satellite cells are added to myofibers and contribute myonuclei, it was hypothesized that a decline in satellite cell replenishment of myonuclei contributed to sarcopenia 22,23) . In fact, a recent study clearly showed that the number of satellite cells decreases with age, and muscle regeneration is insufficient in aged mice 24) .…”