Effect of CCL11 on In Vitro Myogenesis and Its Clinical Relevance for Sarcopenia in Older Adults

Abstract

Background:The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor. Accordingly, it may be involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this potential, we investigated the effects of CCL11 on in vitro muscle biology and its clinical relevance for sarcopenia parameters in older adults. Methods: Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Human blood samples were collected from 79 participants who underwent a functional assessment. Thereafter, CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was defined using the Asian-specific guideline. Results: Recombinant CCL11 treatment significantly stimulated myogenesis in a dose-dependent manner, and consistently increased the expression of myogenic differentiation markers. Among the C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells. Further, the CCR5 inhibitor blocked recombinant CCL11-stimulated myogenesis. In a clinical study, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, and poor physical performance, and was not associated with skeletal muscle index, grip strength, short physical performance battery score, gait speed, and time to complete 5 chair stands, after adjusting for sex, age, and body mass index. Conclusion: Contrary to expectations, CCL11 exerted beneficial effects on muscle metabolism at least in vitro system. However, its impact on human muscle health was not evident, suggesting that circulating CCL11 may not be a useful biomarker for sarcopenia risk assessment in older adults.

Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization

“…MIP1b may also play a role in sarcopenia by binding to CCR5, as CCR5 is expressed in muscle cells, and inhibiting CCR5 may block the myogenesis stimulated by CCL11. 33 …”

“…One possible mechanism by which MIP1b may contribute to sarcopenia is through the recruitment and activation of immune cells, such as macrophages and T cells, in affected muscle tissues. MIP1b may also play a role in sarcopenia by binding to CCR5, as CCR5 is expressed in muscle cells, and inhibiting CCR5 may block the myogenesis stimulated by CCL11 33 …”

C–C motif chemokine CCL11 is a novel regulator and a potential therapeutic target in non-alcoholic fatty liver disease

“… 68 CCL11 has also been shown to regulate skeletal muscle phenotypes in both physiological and disease settings. 69 , 70 Targeted deletion of CCL11 and/or CCR3 in adipocytes/skeletal muscle cells would shed further light on how CCL11 signalling contributes to insulin resistance. Second, it was observed that CCL11 deletion or long-term (9-wk) CCR3 antagonism simultaneously suppressed body weight gain and attenuated NAFLD in mice whereas CCL11 neutralisation or short-term (3-wk) CCR3 antagonism ameliorated NAFLD without altering body weight.…”

Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor

“…The area of the MyHC-stained myotubes was calculated using the ZEN 2 (blue edition) software (Carl Zeiss). Fusion index (%) was calculated using the following equation: 100×number of nuclei in MyHC + myotubes per total number of nuclei in MyHC + myocytes and myotubes [ 17 ].…”