Klotho (biology)

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klotho
Identifiers
Symbol KL
Entrez 9365
HUGO 6344
OMIM 604824
RefSeq NM_004795
UniProt Q9UEF7
Other data
Locus Chr. 13 q12

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.

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.

Klotho-deficient mice show increased production of vitamin D, and altered mineral-ion homeostasis is suggested to be a cause of premature aging–like phenotypes, because the lowering of vitamin D activity, either by dietary restriction or FGF-23 ablation, rescues the premature aging–like phenotypes and prolongs survival in these mutants.These results suggest that aging–like phenotypes were due to klotho-associated vitamin D metabolic abnormalities(hypervitaminosis)[5][6].

[edit] 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
  5. ^ Tsujikaw et al., Klotho, a gene related to a syndrome resembling human premature aging, functions in a negative regulatory circuit of vitamin D endocrine system. Molecular Endcrinology 17(12): 2393-2403, 2003.
  6. ^ Akihiro Imura, Yoshihito Tsuji, Miyahiko Murata, Ryota Maeda, Koji Kubota, Akiko Iwano, Chikashi Obuse, Kazuya Togashi, Makoto Tominaga, Naoko Kita, Ken-ichi Tomiyama, Junko Iijima, Yoko Nabeshima, Makio Fujioka, Ryo Asato, Shinzo Tanaka, Ken Kojima, Juichi Ito, Kazuhiko Nozaki, Nobuo Hashimoto, Tetsufumi Ito, Takeshi Nishio, Takashi Uchiyama, Toshihiko Fujimori, Yo-ichi Nabeshima, α-Klotho as a Regulator of Calcium Homeostasis ,Science, Vol. 6, pp 1615 - 1618, 2007. PMID 17569864

[edit] External links