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Sirtuins are a conserved protein family with pleiotropic effects on the regulation of cellular function. Initially identified as the silent information regulator 2 (Sir2) in yeast, which regulates transcriptional silencing of mating-type loci, telomeres, and ribosomal DNA, the sirtuin field received a big boost after the discovery of its life- span- enhancing effect. Indeed, not only in yeast, but also in other simple organisms like flies and worms, sirtuin activation leads to longer life similar to caloric restric- tion, the only physiological way to extend life-span. This opened up a hunt for the mechanisms underlying the sirtuin effect. Sir2 was described as an NAD-dependent histone deacetylase, suggesting that sirtuins integrate metabolic cues into transcrip- tional adaptations. In the years to follow, it became apparent that sirtuins indeed serve as metabolic sensors, but their functional output is not restricted to histones and includes a variety of metabolic regulatory proteins. Considering their role in metabolic regulation, the sirtuins were particularly studied in the context of metabolic disease. The prime focus was on mammalian SIRT1, which is most homologous of Sir2 and epitomizes the seven mammalian sirtuin family members. The development of SIRT1 activators spurred this research area even further, as these compounds prevent the negative effects of diet-induced obesity. Several nutraceutical or pharmaceutical sirtuin activators proved successful in mitigating the effects of such Westernized diets.




Sirtuins. (2016). Sirtuins. Springer Netherlands.

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