Klotho (biology)

The Klotho gene codes for a transmembrane protein that, in addition to other effects, provides some control over the sensitivity of the organism to insulin and appears to be involved in aging. Its discovery was documented in 1997 by Kuro-o et al.^[1] The name of the gene comes from Klotho or Clotho, one of the Moirae, or Fates, in Greek mythology.

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The Klotho protein is a novel β-glucuronidase (EC number 3.2.1.21) capable of hydrolyzing steroid β-glucuronides. Genetic variants in KLOTHO have been associated with human aging^[2], and Klotho protein has been shown to be a circulating factor detectable in serum that declines with age.^[3] Klotho-deficient mice manifest a syndrome resembling accelerated human aging and display extensive and accelerated arteriosclerosis. Additionally, they exhibit impaired endothelium dependent vasodilation and impaired angiogenesis, suggesting that Klotho protein may protect the cardiovascular system through endothelium-derived NO production.

Although the vast majority of research has been based on lack of Klotho, it was demonstrated that an overexpression of Klotho in mice might extend their average life span between 19% and 31% compared to normal mice^[4]. However, the actual use of overexpressing Klotho for extending life-span without side-effects is still a matter of speculation and remains to be justified by further experimentation.

References

1. ^ Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. 1997. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390: 45-51. DOI 10.1038/36285
2. ^ Arking DE, Krebsova A, Macek M Sr, Macek M Jr, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC. Association of human aging with a functional variant of klotho. Proc Natl Acad Sci U S A. 2002; 99: 856–861. PMID 11792841
3. ^ Xiao NM, Zhang YM, Zheng Q, Gu J. Klotho is a serum factor related to human aging. Chin Med J (Engl). 2004; 117: 742–747.
4. ^ Kurosu et al, Suppression of Aging in Mice by the Hormone Klotho, Science, 25 August 2005. PMID 16123266