Physiology: Suppression of aging in mice by the hormone Klotho

Hiroshi Kurosu; Masaya Yamamoto; Jeremy D. Clark; Johanne V. Pastor; Animesh Nandi; Prem Gurnani; Owen P. McGuinness; Hirotaka Chikuda; Masayuki Yamaguchi; Hiroshi Kawaguchi; Iichiro Shimomura; Yoshiharu Takayama; Joachim Herz; C. Ronald Kahn; Kevin P. Rosenblatt; Makoto Kuro-O

doi:10.1126/science.1112766

Physiology: Suppression of aging in mice by the hormone Klotho

Hiroshi Kurosu, Masaya Yamamoto, Jeremy D. Clark, Johanne V. Pastor, Animesh Nandi, Prem Gurnani, Owen P. McGuinness, Hirotaka Chikuda, Masayuki Yamaguchi, Hiroshi Kawaguchi, Iichiro Shimomura, Yoshiharu Takayama, Joachim Herz, C. Ronald Kahn, Kevin P. Rosenblatt, Makoto Kuro-O

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Abstract

A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (ICF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and ICF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.

Original language	English (US)
Pages (from-to)	1829-1833
Number of pages	5
Journal	Science
Volume	309
Issue number	5742
DOIs	https://doi.org/10.1126/science.1112766
State	Published - Sep 16 2005

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title = "Physiology: Suppression of aging in mice by the hormone Klotho",

abstract = "A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (ICF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and ICF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.",

author = "Hiroshi Kurosu and Masaya Yamamoto and Clark, {Jeremy D.} and Pastor, {Johanne V.} and Animesh Nandi and Prem Gurnani and McGuinness, {Owen P.} and Hirotaka Chikuda and Masayuki Yamaguchi and Hiroshi Kawaguchi and Iichiro Shimomura and Yoshiharu Takayama and Joachim Herz and Kahn, {C. Ronald} and Rosenblatt, {Kevin P.} and Makoto Kuro-O",

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doi = "10.1126/science.1112766",

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T2 - Suppression of aging in mice by the hormone Klotho

AU - Kurosu, Hiroshi

AU - Yamamoto, Masaya

AU - Clark, Jeremy D.

AU - Pastor, Johanne V.

AU - Nandi, Animesh

AU - Gurnani, Prem

AU - McGuinness, Owen P.

AU - Chikuda, Hirotaka

AU - Yamaguchi, Masayuki

AU - Kawaguchi, Hiroshi

AU - Shimomura, Iichiro

AU - Takayama, Yoshiharu

AU - Herz, Joachim

AU - Kahn, C. Ronald

AU - Rosenblatt, Kevin P.

AU - Kuro-O, Makoto

PY - 2005/9/16

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N2 - A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (ICF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and ICF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.

AB - A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (ICF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and ICF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.

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Physiology: Suppression of aging in mice by the hormone Klotho

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