Title:Intracellular Signaling of the Aging Suppressor Protein Klotho
Volume: 15
Issue: 1
Author(s): M. Sopjani, M. Rinnerthaler, J. Kruja and M. Dermaku-Sopjani
Affiliation:
Keywords:
cAMP, fibroblast growth factor (FGF), insulin/IGF-1, Klotho, PKC, PTH, vitamin D, p53/p21, Wnt
signaling pathway.
Abstract: The Klotho protein deficiency is known to participate in premature aging. As
an aging suppressor, Klotho is an important molecule in aging processes and its overexpression
results in longevity. Due to many reasons, the insulin/insulin-like growth
factor-1 (IGF-1) has been considered as a key pathway in aging research. The Klotho
gene is closely related to this pathway. The Klotho gene encodes a transmembrane
protein that after cleavage is also found as a secreted protein. Importantly, its overexpression
suppresses insulin/IGF-1 signaling and thus extends the lifespan. In
addition, Klotho participates in the regulation of several other intracellular signaling
pathways, including regulation of FGF23 signaling, cAMP, PKC, transforming growth
factor-β (TGF-β), p53/p21, and Wnt signaling. The aim of this review is to summarize
current literature that shows the involvement of Klotho in the regulation of several
intracellular pathways. The results of our review clearly indicate that Klotho participates in several intracellular
signaling pathways, and by regulating them, Klotho is involved in aging and longevity.
