Abstract
Aging causes a decline in skeletal muscle function, resulting in a progressive loss of muscle mass, quality, and strength. A weak regenerative capacity is one of the critical causes of dysfunctional skeletal muscle in elderly individuals. The extracellular matrix (ECM) maintains the tissue framework structure in skeletal muscle. As shown by previous reports and our data, the gene expression of ECM components decreases with age, but the accumulation of collagen substantially increases in skeletal muscle. We examined the structural changes in ECM in aged skeletal muscle and found restricted ECM degradation. In aged skeletal muscles, several genes that maintain ECM structure, such as transforming growth factor β (TGF-β), tissue inhibitors of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs), and cathepsins, were downregulated. Muscle injury can induce muscle repair and regeneration in young and adult skeletal muscles. Surprisingly, muscle injury could not only efficiently induce regeneration in aged skeletal muscle, but it could also activate ECM remodeling and the clearance of ECM deposition. These results will help elucidate the mechanisms of muscle fibrosis with age and develop innovative antifibrotic therapies to decrease excessive collagen deposition in aged muscle.
Highlights
The extracellular matrix (ECM) of skeletal muscle maintains tissue integrity and provides structural support [1,2]
A decline in regeneration leads to the accumulation of adipose tissues and collagen
Collagen accumulation was observed in muscle fibers, including the endomysium and perimysium, in the aged skeletal muscles compared with the young skeletal muscles (Figure 1A)
Summary
The ECM of skeletal muscle maintains tissue integrity and provides structural support [1,2]. Collagen I has been reported to be predominant in the perimysium, whereas collagen III is prevalent in the endomysium and the epimysium [2,10] Networking collagens such as collagen IV are expressed mainly in the basement membrane (BM) [11,12], and collagens VI, XV, and XVIII are present in the BM of skeletal muscle [13]. MuSCs activate, proliferate and fuse to form regenerated myofibers that facilitate repair via increased expression of certain myogenic regulation factor genes [17,18]. Alterations in the collagen network, an extrinsic factor, may contribute to the deterioration of muscle mechanical properties with aging These structural and biochemical changes in the ECM of aged skeletal muscle may lead to increased stiffness and impairment of force generation by muscle fibers [4]. This study may provide a therapeutic strategy to decrease collagen accumulation in the skeletal muscle of elderly individuals and recover muscle functions
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