Regulation of oxidative stress by the anti-aging hormone Klotho

被引：573

作者：

Yamamoto, M ^{[1
]}

Clark, JD ^{[1
]}

Pastor, JV ^{[1
]}

Gurnani, P ^{[1
]}

Nandi, A ^{[1
]}

Kurosu, H ^{[1
]}

Miyoshi, M ^{[1
]}

Ogawa, Y ^{[1
]}

Castrillon, DH ^{[1
]}

Rosenblatt, KP ^{[1
]}

Kuro-o, M ^{[1
]}

机构：

[1] Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2005年 / 280卷 / 45期

基金：

美国国家科学基金会;

关键词：

D O I：

10.1074/jbc.M509039200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

klotho is an aging suppressor gene and extends life span when overexpressed in mice. Klotho protein was recently demonstrated to function as a hormone that inhibits insulin/insulin-like growth factor-1 (IGF-1) signaling. Here we show that Klotho protein increases resistance to oxidative stress at the cellular and organismal level in mammals. Klotho protein activates the FoxO forkhead transcription factors that are negatively regulated by insulin/IGF-1 signaling, thereby inducing expression of manganese superoxide dismutase. This in turn facilitates removal of reactive oxygen species and confers oxidative stress resistance. Thus, Klotho-induced inhibition of insulin/IGF-1 signaling is associated with increased resistance to oxidative stress, which potentially contributes to the anti-aging properties of klotho.

引用

页码：38029 / 38034

页数：6

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