In Vitro Effect of CCL11 on Myogenic Differentiation and Its Relevance With Sarcopenia Parameters in Older Adults

Background: The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor and thus may be also involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this possibility, we investigated the effects of CCL11 on in vitro muscle biology and clinical relevance with sarcopenia parameters in older adults. Methods: Primary mouse myoblasts and C2C12 cells were used for experimental research. Blood samples were collected from 79 participants who underwent a functional assessment, and CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was diagnosed using the Asian-specific cut-off points. Results: CCL11 treatment stimulated the differentiation of both primary myoblasts and C2C12 cells into mature myotubes, and consistently increased the expression of myogenic differentiation markers, such as myosin heavy chain and myogenin. Among C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells, and CCR5 inhibitor blocked CCL11-stimulated myogenesis. In a clinical study, after adjustment for sex, age, and body mass index, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, low muscle strength, and low physical performance, and was not associated with any of skeletal muscle index, grip strength, gait speed, time to complete 5 chair stands, and short physical performance battery score. Conclusions: Contrary to expectations, CCL11 showed the beneficial effects on muscle metabolism at least in vitro system. However, the role of CCL11 on muscle health in humans was not evident, suggesting that circulating CCL11 level may not be a useful biomarker for sarcopenia risk assessment in older adults.