KL and chronic kidney disease: In a state of a Klotho deficiency, such as CKD and older age, enhancing circulating levels of Klotho and endogenous production of Klotho in skeletal muscle may prevent or reverse sarcopenia by preventing skeletal muscle fibrosis in favor of effective regeneration, improving muscle mitochondrial bioenergetics, and protecting muscle against oxidative damage and systemic inflammation (Figure 1).