Intrinsic Changes and Extrinsic Influences of Myogenic Stem Cell Function During Aging

Abstract

The myogenic stem cell (satellite cell) is almost solely responsible for the remarkable regeneration of adult skeletal muscle fibers after injury. The availability and the functionality of satellite cells are the determinants of efficient muscle regeneration. During aging, the efficiency of muscle regeneration declines, suggesting that the functionality of satellite cells and their progeny may be altered. Satellite cells do not sit in isolation but rather are surrounded by, and influenced by, many extrinsic factors within the muscle tissue that can alter their functionality. These factors likely change during aging and impart both reversible and irreversible changes to the satellite cells and on their proliferating progeny. In this review, we discuss the possible mechanisms of impaired muscle regeneration with respect to the biology of satellite cells. Future studies that enhance our understanding of the interactions between stem cells and the environment in which they reside will offer promise for therapeutic applications in age-related diseases.

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

“…It is widely accepted that defective proliferation and/ or differentiation potential of SCs represent a major cause of sarcopenia in otherwise healthy aged people (Brack and Rando 2007;Conboy and Rando 2005;Gopinath and Rando 2008). However, the molecular mechanisms underpinning these age-related changes Fig.…”

“…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.…”

BAF60 A, B, and Cs of muscle determination and renewal

“…Together, these findings suggest that telomere shortening depletes the pool of satellite cells. In addition, degradation of the cellular environment, or niche, might contribute to the decline in regenerative potential with age or chronic disease (Conboy and Rando 2005;Brack and Rando 2007;Gopinath and Rando 2008). Environmental changes that alter extrinsic cues controlling satellite cell function might reflect an adaptive mechanism that becomes maladaptive when chronically activated.…”

Cell intrinsic and extrinsic mechanisms of stem cell aging depend on telomere status

“…In aging mammals, the functional reserve of adult stem cells decreases in the hematopoietic system (Waterstrat et al, 2008. ), in pancreatic islets , in areas of neurogenesis in the brain (Molofsky et al, 2006), in hair follicles (Nishimura et al, 2005), in intestinal crypts (Martin et al, 1998), and in muscle (Brack and Rando, 2007).…”