Down-Regulation of Soluble α-Klotho is Associated with Reduction in Serum Irisin Levels in Chronic Obstructive Pulmonary Disease

The klotho gene was originally identified as a putative aging-suppressor gene. Klotho-depleted mice display a shortened life span and exhibit a variety of premature aging-related phenotypes such as pulmonary emphysema and sarcopenia. This study was designed to determine the roles of secreted-type klotho protein on lung and skeletal muscle in chronic obstructive pulmonary disease (COPD). Serum alpha-klotho and irisin levels were assayed in 16 non-smokers, 13 smokers without COPD, and 24 smokers with COPD. Moreover, we examined correlations between soluble alpha-klotho levels and the results of lung function test, cardiopulmonary exercise test (CPET), and skeletal muscle function in smokers with COPD. Soluble alpha-klotho levels were significantly lower in smokers with COPD compared to non-smokers and smokers without COPD. In smokers with COPD, those levels did not significantly correlate with any parameters of lung function test. In CPET, peak VO2 significantly correlated with FEV1 (% predicted) (r = 0.76, p = 0.0003) and DLCO (% predicted) (r = 0.62, p = 0.003). In contrast, soluble alpha-klotho levels did not significantly correlate with peak VO2. Irisin levels were also significantly lower in smokers with COPD. Moreover, there was a significant correlation between soluble alpha-klotho and serum irisin levels (r = 0.61, p = 0.004). Our findings could provide a critical first step to understanding the impacts of soluble alpha-klotho on skeletal muscle in COPD and may lead to the identification of new molecular targets for the treatment of COPD.