1. [Klotho not only antiageing protein].
- Author
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Sosnowski B, Bachórzewska-Gajewska H, Dobrzycki S, and Malyszko J
- Subjects
- Aging, Animals, Cardiovascular Diseases enzymology, Cardiovascular Diseases metabolism, Fibroblast Growth Factor-23, Glucuronidase physiology, Homeostasis, Humans, Hypertension enzymology, Hypertension metabolism, Klotho Proteins, Mice, Osteoporosis enzymology, Osteoporosis metabolism, Signal Transduction, Calcium metabolism, Glucuronidase metabolism, Phosphates metabolism
- Abstract
Klotho, the gene encoding the antiaging protein, was discovered in 1997 and named after a Greek Goddes who spun the thread of life. Numerous experiments on mice confirmed that destruction of the klotho gene or loss of klotho function leads to an accelerated aging and premature death. In addition to shortened life span, klotho-deficient mice demonstrated changes in functioning of multiple organs, ectopic calcification, enhanced development of arteriosclerosis, osteoporosis and atrophy of skin. In contrast, overexpression of a gene in mice inhibited aging and prolonged survival. The multisystemic phenotype induced by Klotho deficiency indicates that Klotho works on a variety of organs. Klotho is highly expressed in the kidney, brain, and to a lesser extent in other organs. Protein Klotho exists in two forms: membrane and secreted which play different functions. Membrane Klotho function as an obligate co-receptor required for signaling for the phosphaturic factor FGF23, regulates calcium-phosphate homeostasis through renal ion transport in addition to modulation of PTH and 1,25(OH)2D3. Soluble klotho functions as a humoral factor and regulates the activity of several ion channels and transporters. The secreted Klotho can also inhibit oxydative stres and the insulin and insulin-like growth factor 1 (IGF-1) pathways. The discovery of the protein klotho led to the identification of new axes connecting endocrine disturbances in the homeostasis of the calcium-phosphate to the aging of the organism. Klotho deficiency may not only be a trigger for accelerated aging but also in development of age- -associated diseases, including hypertension, osteoporosis, cardiovascular disease, and CKD. Conceivably, better understanding of Klotho protein might provide a novel treatment strategy for aging and age-associated diseases.
- Published
- 2017