TY - JOUR
T1 - Regulation of oxidative stress by the anti-aging hormone klotho
AU - Yamamoto, Masaya
AU - Clark, Jeremy D.
AU - Pastor, Johanne V.
AU - Gurnani, Prem
AU - Nandi, Animesh
AU - Kurosu, Hiroshi
AU - Miyoshi, Masayoshi
AU - Ogawa, Yasushi
AU - Castrillon, Diego H.
AU - Rosenblatt, Kevin P.
AU - Kuro-O, Makoto
PY - 2005/11/11
Y1 - 2005/11/11
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M509039200
DO - 10.1074/jbc.M509039200
M3 - Article
C2 - 16186101
AN - SCOPUS:27844561111
SN - 0021-9258
VL - 280
SP - 38029
EP - 38034
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 45
ER -