THE RELATIONSHIP BETWEEN CAPILLARIES AND MUSCLE STEM CELLS: CONSEQUENCES FOR ADAPTATION, REPAIR AND AGING

Abstract

Skeletal muscle possesses a remarkable plasticity, able to repair, remodel and adapt to various stressors. A population of resident muscle stem cells, commonly referred to as satellite cells (SC), are largely responsible for skeletal muscle plasticity. The loss of muscle mass and plasticity typically observed in aging has been attributed to the deterioration of SC function. SC reside in a quiescent state, but following stimuli they become active, proliferate and eventually differentiate, fusing to existing muscle fibres. The progression of SC through this process, termed the myogenic program, is orchestrated by a complex network of transcription factors, termed myogenic regulatory factors. SC function is regulated by various growth factors and/or cytokines. The delivery of these signalling factors to SC is, in part, dependent on their proximity and exposure to local microvascular blood flow. The purpose of this thesis was to examine the relationship between skeletal muscle capillaries and muscle SC. We examined the effect of age on the spatial relationship between SC and muscle fiber capillaries, and observed that type II muscle fiber SC were located at a greater distance from the nearest capillary in older men as compared to their younger counterparts. We then examined the changes in SC activation status following a single bout of resistance exercise, prior to and following a 16wk progressive resistance training (RT) program. We observed that following RT, there was an enhanced SC activation in response to a single bout of resistance exercise. This enhanced response was accompanied by an increase in muscle capillarization following training. Furthermore, we investigated the impact of muscle fiber capillarization on the expansion and activation status of SC in acute response to muscle damaging exercise in healthy young men. We observed that muscle capillarization was positively related to SC pool activation and expansion. Taken together, we demonstrate that muscle capillarization may be related to the SC response following acute resistance exercise or exercise-induced injury, and may be implicated in adaptation to RT. Furthermore, the spatial relationship between muscle capillaries and SC is negatively altered by aging.