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 (IGF1), 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 IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / genetics
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Aging / physiology*
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Animals
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Blood Glucose / analysis
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Cell Line
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Cell Line, Tumor
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Eating
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Female
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Glucuronidase
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Insulin / blood
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Insulin / metabolism
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Insulin Resistance
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Insulin-Like Growth Factor I / metabolism
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Insulin-Like Growth Factor I / pharmacology
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Klotho Proteins
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Ligands
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Longevity / genetics
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Longevity / physiology*
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Male
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Membrane Proteins / chemistry
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Membrane Proteins / genetics*
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Membrane Proteins / pharmacology
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Membrane Proteins / physiology*
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Mice
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Mice, Transgenic
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Myoblasts / metabolism
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Oxygen Consumption
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Peptide Fragments / chemistry
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Peptide Fragments / pharmacology
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Phosphorylation
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Receptor, IGF Type 1 / metabolism
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Receptor, Insulin / metabolism
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Receptors, Cell Surface / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Signal Transduction
Substances
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Blood Glucose
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Insulin
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Ligands
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Membrane Proteins
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Peptide Fragments
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Receptors, Cell Surface
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Recombinant Proteins
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Insulin-Like Growth Factor I
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Receptor, IGF Type 1
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Receptor, Insulin
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Glucuronidase
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Klotho Proteins