Abstract
Advanced age causes skeletal muscle to undergo deleterious changes including muscle atrophy, fast-to-slow muscle fiber transition, and an increase in collagenous material that culminates in the age-dependent muscle wasting disease known as sarcopenia. Advanced glycation end-products (AGEs) non-enzymatically accumulate on the muscular collagens in old age via the Maillard reaction, potentiating the accumulation of intramuscular collagen and stiffening the microenvironment through collagen cross-linking. This review contextualizes known aspects of skeletal muscle extracellular matrix (ECM) aging, especially the role of collagens and AGE cross-linking, and underpins the motor nerve’s role in this aging process. Specific directions for future research are also discussed, with the understudied role of AGEs in skeletal muscle aging highlighted. Despite more than a half century of research, the role that intramuscular collagen aggregation and cross-linking plays in sarcopenia is well accepted yet not well integrated with current knowledge of AGE’s effects on muscle physiology. Furthermore, the possible impact that motor nerve aging has on intramuscular cross-linking and muscular AGE levels is posited.
Highlights
Musculoskeletal injury increases due to falls and other accidental injuries in old age, and age-dependent alterations to skeletal muscle structure and function are the primary causal factors of such incidents [1]
The entire muscle is encased by the epimysium, which consists of type I and III collagen fibers that run perpendicular to the muscle and are responsible for maintaining the muscle girth [13,25,26]
P-38 mitogen activated protein kinase (MAPK) phosphorylation is upregulated by Advanced glycation end-products (AGEs)-receptor for advanced-glycation end-products (RAGE) signaling and elevated p-38 MAPK signaling been implicated as a factor that disrupts satellite cell signaling in old age [52,58,61]
Summary
Musculoskeletal injury increases due to falls and other accidental injuries in old age, and age-dependent alterations to skeletal muscle structure and function are the primary causal factors of such incidents [1]. Non-enzymatic cross-linking by AGEs decrease collagen’s susceptibility to degradation by matrix metalloproteinases, causing the build-up of collagen and subsequent stiffening of the usually pliant skeletal muscle ECM [13]. Bioengineering 2021, 8, 168 fewer that address the role of AGEs in sarcopenic decline [14,15,16,17,18,19]. It has been 10 years since the last time this topic was reviewed in-depth, a purview of the literature in this space is warranted [20]. Muscle-nerve interactions play an integral role in muscle health, and a discussion of motor neurons is included in this review in support of the critical role that AGEs have in the aging motor endplate
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