Skeletal muscle collagen: Age, injury and disease

Abstract

Collagen is the most common protein of the extracellular matrix and has several important functions in skeletal muscle, including the provision of both tensile strength and elasticity, the transmission of muscular forces to the bones, the regulation of cell attachment and differentiation, and mechanical and ionic filtration by the basal lamina. Aging is associated with significant changes in the connective tissue compartment of skeletal muscle. This chapter describes the effect of aging on skeletal muscle collagen, how injury affects collagen metabolism, how collagen is remodeled with advancing age and in severe muscle diseases like Duchenne muscular dystrophy. The regulation of collagen metabolism in normal and damaged skeletal muscle is complex and likely involves the interaction of several cell types and growth factors. Muscles with different activation patterns exhibit marked differences in collagen mRNA levels as well as collagen characteristics, indicating that mechanical load mediates collagen biosynthesis. Injured skeletal muscle contains elevated levels of inflammatory cells, which are known to secrete pro- and anti-inflammatory cytokines. Chronic inflammation plays a key role in the development of fibrosis in dystrophic muscle, although the mechanisms that regulate this process are not well understood. Both neutrophils and macrophages play important roles in the regulation of collagen remodeling post-injury by releasing various cytokines that mediate the behavior of inflammatory cells, fibroblasts and satellite cells. The behavior of these cells can be affected by extrinsic factors such as basal levels of growth hormone, which also changes with advancing age.