Klotho (biology) 2540680 220674152 2008-06-21T00:39:38Z Crackles 5741080 Fgf-23 ablation leads to increased synthesis of vitamin D (not decreased) -Razzaque, M., et. al FGF-23, Vitamin D, and calcification: the unholy triad, Nephrol Dial Transplant, (2005) 20: 2032-2035 {{protein |Name=klotho |caption= |image= |width= |HGNCid=6344 |Symbol=KL |AltSymbols= |EntrezGene=9365 |OMIM=604824 |RefSeq=NM_004795 |UniProt=Q9UEF7 |PDB= |ECnumber= |Chromosome=13 |Arm=q |Band=12 |LocusSupplementaryData= }} 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''.<ref>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</ref> 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]] [[glucuronide|β-glucuronides]]. Genetic variants in ''KLOTHO'' have been associated with human aging<ref>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</ref>, and Klotho protein has been shown to be a circulating factor detectable in [[blood plasma|serum]] that declines with age.<ref>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.</ref> 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 [[Nitric oxide|NO]] production. Although the vast majority of research has been based on lack of Klotho, it was demonstrated that an overexpression of Klotho in [[House Mouse|mice]] might extend their [[average life span]] between 19% and 31% compared to normal mice<ref>Kurosu et al, Suppression of Aging in Mice by the Hormone Klotho, ''Science'', 25 August 2005. PMID 16123266</ref>. 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 by dietary restriction reverses 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)<ref>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.</ref><ref>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</ref>. ==References== <references/> ==External links== * [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9365 Entrez Gene entry for Klotho] * [http://genomics.senescence.info/genes/entry.php?hugo=KL GenAge entry for Klotho] [[Category:Gerontology]][[Category:EC 3.2.1]][[Category:Genes]] [[fr:Gène klotho]] [[ru:Клото (белок)]]