Stem Cell Review Series: Aging of the skeletal muscle stem cell niche

Abstract

SummaryDeclining stem cell function during aging contributes to impaired tissue function. Muscle-specific stem cells ('satellite cells') are responsible for generating new muscle in response to injury in the adult. However, aged muscle displays a significant reduction in regenerative abilities and an increased susceptibility to age-related pathologies. This review describes components of the satellite cell niche and addresses how age-related changes in these components impinge on satellite cell function. In particular, we review changes in the key niche elements, the myofiber and the basal lamina that are in intimate contact with satellite cells. We address how these elements are influenced by factors secreted by interstitial cells, cells of the immune system, and cells associated with the vasculature, all of which change with age. In addition, we consider more distant sources of influence on the satellite cell niche that change with age, such as neural-mediated trophic factors and electrical activity and systemic factors present in the circulation. A better understanding of the niche elements and their influence on the satellite cell will facilitate the development of therapeutic interventions aimed at improving satellite cell activity and ultimately tissue response to injury in aged individuals.

Elevated SOCS3 and altered IL-6 signaling is associated with age-related human muscle stem cell dysfunction

“…This may be partially explained by the elevated basal SOCS3 in the muscle, which may have desensitized the SCs to IL-6 (20,62). The muscle stem cell niche is sensitive to age-related alterations in signaling molecules (15,23) and thus chronically elevated muscle IL-6 (as demonstrated at the mRNA level) may have negatively impacted the microenvironment of the SCs, impairing normal IL-6 signaling. This hypothesis is supported by the blunted induction of pSTAT3 in the type II-associated SCs in older muscle at 3 h postexercise.…”

Muscle stem cells and reversible quiescence: The role of sprouty

“…29,48 Other muscle resident cell types which are considered part of the satellite cell niche have been discussed elsewhere. 49,50 However, satellite cells are capable of self-renewal and differentiation during repair. 20,21 This confirms that adult Pax7 + satellite cells have stem cell properties in their endogenous environment.…”

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

“…By contrast, there is consensus regarding an age-related decline in the performance of SCs as a primary cause of sarcopenia. In this regard, both extrinsic factors of the extracellular environment (the so-called SC "niche") and intrinsic properties of the SCs have been proposed to contribute to sarcopenia (Brack and Rando 2007;Conboy and Rando 2005;Gopinath and Rando 2008). While several works have documented relevant changes in the SC niche during aging (Brack and Rando 2007 and Refs.…”