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Science 17 December 2004:
Vol. 306. no. 5704, p. 1997
DOI: 10.1126/science.306.5704.1997n

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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. (p. 2105) 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.





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Science. ISSN 0036-8075 (print), 1095-9203 (online)