Effect of CCL11 on In Vitro Myogenesis and Its Clinical Relevance for Sarcopenia in Older Adults. Endocrinol Metab (Seoul). 2021 [참여저자]

Da Ae Kim,1,* So Jeong Park,1,* Jin Young Lee,1 Jeoung Hee Kim,2 Seungjoo Lee,2 Eunju Lee,3 Il-Young Jang,3 Hee-Won Jung,3 Jin Hoon Park,2 and Beom-Jun Kim4

doi: 10.3803/EnM.2020.942

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.

Keywords: Chemokine CCL11, Muscle development, Sarcopenia, Aging, Biomarkers

Fig. 3

Differences in serum C-C motif chemokine ligand 11 (CCL11) levels based on the status of sarcopenia and related parameters (A) before and (B) after adjusting for sex, age, and body mass index (BMI). Analysis of covariance was used to generate and compare the estimated means with 95% confidence intervals.