Editors' ChoiceAging

Linking Age Control Mechanisms

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Science's STKE  21 Dec 2004:
Vol. 2004, Issue 264, pp. tw457
DOI: 10.1126/stke.2642004tw457

Four different factors have been linked independently to mammalian aging--nutrient availability, the Forkhead transcription factor Foxo3a, the nicotinamide adenine dinucleotide-dependent deacetylase SIRT1, and the tumor suppressor protein p53. Nemoto et al. now report that these elements intersect in a manner that may modulate mammalian life-span. Under conditions of nutritional stress, Foxo3a stimulates SIRT1 expression in mammalian cells, which requires p53 and two p53-binding sites within the SIRT1 promoter. Moreover, Foxo3a and p53 interaction increases under nutrient-starved conditions. The signaling pathway may constitute a homeostatic regulatory network that responds to nutrient availability and, consequently, controls aging.

S. Nemoto, M. M. Fergusson, T. Finkel, Nutrient availability regulates SIRT1 through a Forkhead-dependent pathway. Science 306, 2105-2108 (2004). [Abstract] [Full Text]

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