Skeletal Muscle Regeneration, Repair and Remodelling in Aging: The Importance of Muscle Stem Cells and Vascularization

Abstract

Sarcopenia is the age-related loss of skeletal muscle mass and strength. Ultimately, sarcopenia results in the loss of independence, which imposes a large financial burden on healthcare systems worldwide. A critical facet of sarcopenia is the diminished ability for aged muscle to regenerate, repair and remodel. Over the years, research has focused on elucidating underlying mechanisms of sarcopenia and the impaired ability of muscle to respond to stimuli with aging. Muscle-specific stem cells, termed satellite cells (SC), play an important role in maintaining muscle health throughout the lifespan. It is well established that SC are essential in skeletal muscle regeneration, and it has been hypothesized that a reduction and/or dysregulation of the SC pool, may contribute to accelerated loss of skeletal muscle mass that is observed with advancing age. The preservation of skeletal muscle tissue and its ability to respond to stimuli may be impacted by reduced SC content and impaired function observed with aging. Aging is also associated with a reduction in capillarization of skeletal muscle. We have recently demonstrated that the distance between type II fibre-associated SC and capillaries is greater in older compared to younger adults. The greater distance between SC and capillaries in older adults may contribute to the dysregulation in SC activation ultimately impairing muscle's ability to remodel and, in extreme circumstances, regenerate. This viewpoint will highlight the importance of optimal SC activation in addition to skeletal muscle capillarization to maximize the regenerative potential of skeletal muscle in older adults.

Factors secreted from high glucose treated endothelial cells impair expansion and differentiation of human skeletal muscle satellite cells

“…Joanisse et al . () reported an increase in the distance between satellite cells and capillaries in older individuals that correlates with decreased capillarization (Joanisse et al . ).…”

“…() reported an increase in the distance between satellite cells and capillaries in older individuals that correlates with decreased capillarization (Joanisse et al . ). To our knowledge, this relationship has not been investigated in skeletal muscle of patients with T2DM or CVD; however, it is possible that increased diffusion distance and decreased capillarization plays a role in altering intracellular cross‐talk in endothelial dysfunction related pathologies.…”

The influence of capillarization on satellite cell pool expansion and activation following exercise‐induced muscle damage in healthy young men

“…; Joanisse et al . ). However, to what extent the muscle fibre microvascular bed may dictate the acute muscle SC response during muscle repair in humans remains unknown.…”

Distinct skeletal muscle molecular responses to pulmonary rehabilitation in chronic obstructive pulmonary disease: a cluster analysis

“…In the older population, which is prone to the loss of muscle mass and strength (i.e. sarcopenia), the exercise response can be blunted due to impaired skeletal muscle regeneration . This potentially results from an impaired induction of skeletal muscle remodelling‐related processes, as reflected by a blunted induction of protein degradation, anabolic resistance, and a delayed or blunted satellite cell response .…”

“…sarcopenia), the exercise response can be blunted due to impaired skeletal muscle regeneration . This potentially results from an impaired induction of skeletal muscle remodelling‐related processes, as reflected by a blunted induction of protein degradation, anabolic resistance, and a delayed or blunted satellite cell response . Similarly, the exercise response in COPD patients may be limited by impaired satellite cell mediated skeletal muscle regeneration .…”