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Klotho RNAi induces premature senescence of human cells via a p53/p21 dependent pathway

2006; Wiley; Volume: 580; Issue: 24 Linguagem: Inglês

10.1016/j.febslet.2006.09.036

1873-3468

Rita Machado de Oliveira,

Renal and related cancers

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 RNAi. 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.