|Organism||Saccharomyces cerevisiae (replicative)|
|Aging Phenotype||Shortened life-span|
|Description||Supplementation of media with 5 mM nicotinamide shortens life-span by approximately 50% (Bitterman et al., 2002). Cells grown in the presence of nicotinamide have a life-span indistinguishable from cells deleted for SIR2, and nicotinamide fails to further shorten the life span of sir2 cells.|
Sir2p is an NAD-dependent histone deacetylase (Imai et al., 2000). Overexpression of Sir2p extends the life-span of mother cells and deletion shortens life-span (Kaeberlein et al., 1999).
Nicotinamide non-competetively inhibits the histone deacetylase activity of Sir2p in vitro (Bitterman et al., 2002). Growth in the presence of nicotinamide increases rDNA recombination and inhibits Sir2p-dependent silencing at the rDNA, telomeres and silent mating loci.
|Primary Reference||Bitterman, K. J., Anderson, R. M., Cohen, H. Y., Latorre-Esteves, M., and Sinclair, D. A. (2002). Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem 277, 45099-107. [Abstract]|
|Other References||Imai, S., Armstrong, C. M., Kaeberlein, M., and Guarente, L. (2000). Transcriptional silencing and longevity protein Sir2 is an NAD- dependent histone deacetylase. Nature 403, 795-800. [Abstract]|
Kaeberlein, M., McVey, M., and Guarente, L. (1999). The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13, 2570-80. [Abstract]
|Keywords||silencing, histone, deacetylase, NAD, calorie, caloric, restriction|