Klotho was serendipitously discovered and labeled an anti-aging gene, because homozygous Klotho hypomorphic mice demonstrated a premature aging-like syndrome whose manifestations include short lifespan, disturbed mineral metabolism including hyperphosphatemia and multiple organ degeneration such as infertility, arteriosclerosis, cardiomyopathy, ectopic calcification, skin atrophy, osteoporosis, and emphysema (Kuro-O et al., 1997). Here, KL is linked to skin atrophy.