Journal
FEBS LETTERS
Volume 580, Issue 24, Pages 5753-5758Publisher
WILEY
DOI: 10.1016/j.febslet.2006.09.036
Keywords
Klotho; senescence; aging; p53; human lung fibroblasts; insulin/IGF-1 signaling
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Klotho has recently emerged as a regulator of aging. To investigate the role of Klotho in the regulation of cellular senescence, we generated stable MRC-5 human primary fibroblast cells knockdown for Klotho expression by RNAL Downregulation of Klotho dramatically induces premature senescence with a concomitant upregulation of p21. The upregulation of p21 is associated with cell cycle arrest at G1/S boundary. Knockdown of p53 in the Klotho attenuated MRC-5 cells restores normal growth and replicative potential. These results demonstrate that Klotho normally regulates cellular senescence by repressing the p53/p21 pathway. Our findings implicate Klotho as a regulator of aging in primary human fibroblasts. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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