Inflammatory pathway communication with skeletal muscle-Does aging play a role? A topical review of the current evidence

Abstract

Skeletal muscle plays an integral role in locomotion, but also as part of the integrative physiological system. Recent progress has identified crosstalk between skeletal muscle and various physiological systems, including the immune system. Both the musculoskeletal and immune systems are impacted by aging. Increased age is associated with decreased muscle mass and function, while the immune system undergoes "inflammaging" and immunosenescence. Exercise is identified as a preventative medicine that can mitigate loss of function for both systems. This review summarizes: (1) the inflammatory pathways active in skeletal muscle; and (2) the inflammatory and skeletal muscle response to unaccustomed exercise in younger and older adults. Compared to younger adults, it appears older individuals have a muted pro-inflammatory response and elevated anti-inflammatory response to exercise. This important difference could contribute to decreased regeneration and recovery following unaccustomed exercise in older adults, as well as in chronic disease. The current research provides specific information on the role inflammation plays in altering skeletal muscle form and function, and adaptation to exercise; however, the pursuit of more knowledge in this area will delineate specific interventions that may enhance skeletal muscle recovery and promote resiliency in this tissue particularly with aging.

Keywords: aging; exercise; inflammation; skeletal muscle.

FIGURE 1

A comparison of younger healthy skeletal muscle and older chronically inflamed skeletal muscle inflammatory response to unaccustomed exercise or exercise with an eccentric contraction component to it (i.e., inflammatory stimuli). Neutrophils are recruited to the site of skeletal muscle damage first via interleukin‐6 (IL‐6) and IL‐8. This stimulates the recruitment of M1 macrophages to the skeletal muscle and activation of the various inflammatory pathways including Janus kinase (JAK)‐signal transducer and activator of transcription (STAT), mitogen‐activated protein kinase (MAPK), and the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB). M1 macrophages (pro‐inflammatory) stimulate the proliferation of satellite cells in skeletal muscle and the inflammatory response via secretion of pro‐inflammatory cytokines. M2 macrophages (anti‐inflammatory and pro‐regenerative) then converge in the area to allow for regeneration of skeletal muscle tissue via the secretion of anti‐inflammatory cytokines. Finally, T cells (specifically T regulatory cells) are recruited to the area of regeneration and signal satellite cells to proliferate and differentiate. Older skeletal muscle that is chronically inflamed typically has less M1 macrophages recruited to the area and an increased proportion of M2 macrophages which may decrease satellite cell proliferation and differentiation and delay regeneration and repair of skeletal muscle.