Suppression of aging in mice by the hormone Klotho.
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.
Kurosu
Hiroshi
H
Department of Pathology, University of Texas (UT) Southwestern Medical Center at Dallas, 5323 Harry Hines Bouleuvard, Dallas, TX 75390-9072, USA.
Yamamoto
Masaya
M
Clark
Jeremy D
JD
Pastor
Johanne V
JV
Nandi
Animesh
A
Gurnani
Prem
P
McGuinness
Owen P
OP
Chikuda
Hirotaka
H
Yamaguchi
Masayuki
M
Kawaguchi
Hiroshi
H
Shimomura
Iichiro
I
Takayama
Yoshiharu
Y
Herz
Joachim
J
Kahn
C Ronald
CR
Rosenblatt
Kevin P
KP
Kuro-o
Makoto
M
D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002460:Cell Line; D045744:Cell Line, Tumor; D004435:Eating; D005260:Female; D005966:Glucuronidase; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D000090265:Klotho Proteins; D008024:Ligands; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D032446:Myoblasts / Q000378:metabolism; D010101:Oxygen Consumption; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D015398:Signal Transduction
D001786:Blood Glucose; D007328:Insulin; D008024:Ligands; D008565:Membrane Proteins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D005966:Glucuronidase; D000090265:Klotho Proteins