What is Klotho?
Klotho, named after the Greek mythological figure, is an enzyme that can be either circulating or bound to cell membranes [1,2]. It is expressed most highly in the kidneys . There are three subfamilies of klotho (α-, ß-, and γ-klotho), with a-klotho being the most prominent.
α-klotho interacts with several proteins, such as activating FGF23 , ROMK , TRPV5 [5, 6], and TRPC6  and antagonizing the Wnt signaling pathway . It appears to play a major role in insulin sensitivity , calcium and phosphate homeostasis [5, 6], oxidative stress and inflammation [2, 8, 9], and cognitive function [10-13]. Reduced klotho accelerates the degenerative process of chronic kidney disease , may be an early sign of oral cancer , and contributes to atherosclerosis [8, 15].
Klotho has received particular attention due to its role in aging. Serum levels of klotho decrease with age in humans  and are predictive of mortality [17-19]. Reduced or absent klotho can be used as an accelerated aging model in mice . On the other hand, an overexpression of klotho can increase mouse lifespan  and genetic variations of the human klotho gene are associated with longer lives .
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 Semba, R.D. et al. Plasma klotho and mortality risk in older community-dwelling adults. J Gerontol A Biol Sci Med Sci (2011). https://doi.org/10.1093/gerona/glr058
 Kresovich, J.K. and Bulka, C.M. Low serum klotho associated with all-cause mortality among a nationally representative sample of American adults. J Gerontol A Biol Sci Med Sci (2021). https://doi.org/10.1093/gerona/glab308
 Kurosu, H. et al. Suppression of aging in mice by the hormone Klotho. Science (2005). https://doi.org/10.1126/science.1112766
Dubal, D.B. et al. Life extension factor klotho enhances cognition. Cell Reports (2014). https://doi.org/10.1016/j.celrep.2014.03.076