Aerobic exercise training increases plasma Klotho levels and reduces arterial stiffness in postmenopausal women

摘要

The Klotho gene was identified originally by insertional mutagenesis in mice that developed multiple aging phenotypes, such as ectopic calcification, osteoporosis, skin atrophy, infertility, and shortened lifespan (19). Klotho transcripts encode membrane-bound and secreted proteins (30), and the extracellular domain of membrane-bound Klotho is processed into the secreted form by ectodomain shedding (4). Klotho is expressed primarily in the kidney, although lower levels of expression have been detected in other organs. Secreted Klotho is detected in the blood, urine, and cerebrospinal fluid (15). Secreted Klotho functions as a humoral factor and is involved in nitric oxide (NO) production in the endothelium (41), regulation of calcium channel activity (16), suppression of oxidative stress (3), transforming growth factor (TGF)-(31 signaling (9), insulin/IGF-I signaling (20). Plasma Klotho concentrations decrease with advancing age in healthy humans (55). Furthermore, it has been reported that the levels of circulating Klotho are lower in certain diseases, such as diabetes, acute kidney injury, and chronic kidney disease (CKD) (8, 13, 44).