Akt negatively regulates the in vitro lifespan of human endothelial cells via a p53/p21-dependent pathway.

ABSTRACT: The signaling pathway of insulin/insulin-like growth factor-1/phosphatidylinositol-3 kinase/Akt is known to regulate longevity as well as resistance to oxidative stress in the nematode Caenorhabditis elegans. This regulatory process involves the activity of DAF-16, a forkhead transcription factor. Although reduction-of-function mutations in components of this pathway have been shown to extend the lifespan in organisms ranging from yeast to mice, activation of Akt has been reported to promote proliferation and survival of mammalian cells. Here we show that Akt activity increases along with cellular senescence and that inhibition of Akt extends the lifespan of primary cultured human endothelial cells. Constitutive activation of Akt promotes senescence-like arrest of cell growth via a p53/p21

SUBMITTER: Miyauchi H 

PROVIDER: S-EPMC1271675 | biostudies-literature | 2004 Jan

REPOSITORIES: biostudies-literature