UCLA

Klotho is a pleiotrophic gene that regulates homeostasis in various tissues. Although Klotho function has been typically viewed in the context of an "anti-aging" molecule, we have observed that its expression in muscle decreases during postnatal muscle development. Here, we report that Klotho has an important role in modulating early muscle growth. In actively growing skeletal muscle, loss of Klotho reduces postnatal myofiber size and overexpression of Klotho increases the size above wild-type levels. Furthermore, the presence of Klotho is required to maintain satellite cell numbers. Klotho enhances skeletal muscle growth by increasing protein content in differentiated myotubes and promoting proliferation of satellite cells. Despite the well-characterized inhibitory relationship between Klotho and IGF-1 signaling in age-related disease models, we find that Klotho upregulates IGF-1 signaling in postnatal skeletal muscle. We conclude that Klotho is not solely a gene that prevents premature aging, rather, it also has an important role in modulating early muscle growth.