Abstract

Introduction: Habitual aerobic exercise leads to reduction of arterial wall thickness and arterial stiffness with aging. Recently, C1q has been identified as a novel myokine, and the expression of muscle C1q mRNA increases with aging. Additionally, in vivo and in vitro studies, C1q induces proliferation of vascular smooth muscle cells. However, it remains unclear whether the secretion of myokines, C1q, TNF-alpha and IL-6 are related to the changes in cardiovascular disease risk by aging and regular exercise. PURPOSE: This study aimed to clarify whether serum C1q, TNF-alpha and IL-6 levels are associated with the changes in cardiovascular disease risks with aging and regular aerobic exercise. Methods: In a cross-sectional study, 127 healthy male and female subjects (18-81 years) were enrolled in this study. Subjects were divided into two groups; young (<40 year) and middle-aged and older (≥40 year) groups. Serum C1q, TNF-alpha, IL-6 levels were determined by ELISA. Risks of cardiovascular disease were estimated by using carotid-femoral pulse wave velocity (cfPWV) and common carotid intima-media thickness (ccIMT). Additionally, in an intervention study, thirteen older male subjects were randomly divided into two groups: aerobic training group (AT: n=6) and a sedentary control group (Con: n=7). subjects in the AT group completed 8 wk of aerobic exercise training (60-70% peak oxygen uptake for 45 min, 3 days/wk). Results: In the cross-sectional study, serum C1q, TNF-alpha and IL-6 levels, cfPWV and ccIMT were significantly higher in middle-aged and older group as compared with young group (respectively p<0.05). Positive correlations between cfPWV and serum C1q (r=0.41, p<0.05), TNF-alpha (r=0.28, p<0.05) or IL-6 (r=0.26, p<0.05) levels were seen. Additionally, ccIMT was positively correlated with only serum C1q (r=0.67, p<0.05). After adjusting for TNF-alpha and IL-6, the association between the serum C1q and cfPWV (ß=0.44, p<0.05) or ccIMT (ß=0.83, p<0.05) remained statistically significant. Additionally, in the intervention study, cfPWV and serum C1q level significantly decreased after AT intervention (each P<0.05). Furthermore, the AT-induced change in serum C1q level was positively correlated with AT-induced change in cfPWV (r=0.65, P<0.05) and ccIMT (r=0.59, P<0.05). Conclusion: These results suggest that circulating C1q level may reflect the changes of arterial stiffness and thickness with aging and regular exercise, and the reduction of serum C1q level in response to regular aerobic exercise may contribute to the reduction in cardiovascular disease risks in the elderly.

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