Leonard Guarente

TL;DR: The analysis of two SIR2 mutations supports the idea that this deacetylase activity accounts for silencing, recombination suppression and extension of life span in vivo, and provides a molecular framework of NAD-dependent histone de acetylation that connects metabolism, genomic silencing and ageing in yeast and, perhaps, in higher eukaryotes.

TL;DR: It is proposed that hSir2, the human homolog of the S. cerevisiae Sir2 protein known to be involved in cell aging and in the response to DNA damage, binds and deacetylates the p53 protein with a specificity for its C-terminal Lys382 residue.

TL;DR: It is shown that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining, and increasing the gene dosage extends the life span in wild-type cells.

TL;DR: It is shown that mammalian Sir2alpha physically interacts with p53 and attenuates p53-mediated functions, and Nicotinamide inhibits an NAD-dependent p53 deacetylation induced by Sir2 alpha, and also enhances the p53 acetylation levels in vivo.

TL;DR: It is shown that the mammalian SIR2 orthologue, Sirt1 (sirtuin 1), activates a critical component of calorie restriction in mammals; that is, fat mobilization in white adipocytes.