In past years researchers have demonstrated in animal studies that reduced levels of klotho can shorten life span while increased levels modestly extend life span. The underlying mechanisms are complex and not fully understood. As is also the case for other longevity-related proteins, altering levels in circulation through gene therapy or other methods changes many aspects of cellular metabolism. Unraveling this complexity is a slow and expensive process. One small part of the bigger picture in this case is the relationship between klotho and fibroblast growth factor 23 (FGF23). The review paper below examines what is known on this topic:
Fibroblast growth factor-23 (FGF23) is a bone-derived hormone known to suppress phosphate reabsorption and vitamin D hormone production in the kidney. Klotho was originally discovered as an anti-aging factor, but the functional role of Klotho is still a controversial issue. Three major functions have been proposed, a hormonal function of soluble Klotho, an enzymatic function as glycosidase, and the function as an obligatory co-receptor for FGF23 signaling. The purpose of this review is to highlight the recent advances in the area of FGF23 and Klotho signaling in the kidney, in the parathyroid gland, in the cardiovascular system, in bone, and in the central nervous system.
Recent advances in the field of FGF23 and Klotho biology have revealed major new functions of FGF23 and Klotho signaling in the kidney, in the heart, in bone, in blood vessels, and in the parathyroid gland. It is now clear that FGF23 is far more than only a phosphaturic bone-derived hormone. Rather, FGF23 has emerged as a pleiotropic endocrine and auto-/paracrine factor not only involved in phosphate homeostasis, but also in calcium and sodium metabolism, in bone mineralization as well as in the development of cardiac hypertrophy. These novel findings have linked phosphate with volume homeostasis, and may have major pathophysiological implications for chronic kidney disease, cardiovascular diseases, and disorders of bone mineralization.