Does resveratrol activate yeast Sir2 in vivo

摘要: In the February issue of Aging Cell , Yang et al . (2007) describe resveratrol derivatives with improved stability and report that they increase yeast replicative lifespan. The authors refer to these drugs as ‘sirtuin activating compounds’, implying lifespan is increased due activation Sir2 histone deacetylase. We applaud development more stable potent analogs. wish point out, however, whether related compounds activate in vivo remains unknown further experimental validation necessary. study well a prior (Howitz ., 2003) are complicated by use PSY316AT strain background. Among strains commonly used aging research, only known case where overexpression fails (Kaeberlein 2004, 2005b). While it possible sirtuin agonist could activity manner not achieved enzyme, also needs be considered (and its analogs) affect longevity Sir2-independent manner. Resveratrol interact variety proteins have homologs, such adenosine monophosphate (AMP) kinase, protein kinase C mitochondrial triphosphate (ATP) synthase, among others & Rabinovitch, 2006). Any potentially mediate effects on cells or other organisms. Another complicating factor sole measure drug activity. clear interest, does imply activity, several single-gene mutations 2005c). can measured directly, for example, monitoring transcription marker genes at telomeres, silent mating loci rDNA (Smith Boeke, 1997; Roy Runge, 2000; Sandmeier 2002; Kaeberlein 2005a). fact, was engineered purpose contains subtelomerically integrated ADE2 marker. Activation enzyme results decreased transcription, which turn causes accumulation red pigment this Visual inspection colonies assays would reveal pigmentation been interest comment assay. It great assess effect Sir2-dependent silencing acetylation each silence. If locus-specific observed, compared between treatments overexpression, provide additional evidence enzymatic enhanced compounds. utility experiments extends beyond simple verification agonists. 2003), suggested activated selective fashion, decreasing recombination without increasing silencing. Increased expression Sir2, contrast, enhances (Fritze Gallo 2004). Thus, reported unexplained, but when considering potential therapeutic applications humans. vitro have, produced ambiguous results: while activates deacetylate fluorescent peptide substrate, either human ortholog SIRT1 towards native substrates (Borra 2005; greet analogs optimism. Thus far, attempts replicate unsuccessful One explanation may unstable over time course required carry out assays. Fortunately, if do should easily detected independently verified using derivatives, most importantly, specific our hope thorough examination will resolve interesting questions.