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Abstract
The sirtuin family of histone deacetylases (HDACs) was named after their homology to the Saccharomyces cerevisiae gene silent information regulator 2 (Sir2). In the yeast, Sir2 has been shown to mediate the effects of calorie restriction on the extension of life span and high levels of Sir2 activity promote longevity. Like their yeast homologs, the mammalian sirtuins (SIRT1‐7) are class III HDACs and require NAD+ as a cofactor to deacetylate substrates ranging from histones to transcriptional regulators. Through this activity, sirtuins are shown to regulate important biological processes ranging from apoptosis, adipocyte and muscle differentiation, and energy expenditure to gluconeogenesis. We review here the current knowledge regarding the role of sirtuins in metabolism, longevity, and discuss the possible therapeutic applications that could result from the understanding of their function in different organs and pathologies.
| Abbreviations | ||
| SIR2 | = | silent information regulator 2 |
| HAT | = | histone acetyltransferase |
| HDAC | = | histone deacetylase |
| CR | = | calorie restriction |
| PKB/AKT | = | protein kinase B |
| GDP | = | guanosine diphosphate |
| GTP | = | guanosine triphosphate |
| NAD+ | = | nicotinamide adenine dinucleotide |
| NADH | = | reduced form of NAD+ |
| Pol II | = | RNA polymerase II |
| TFIIB | = | transcription factor IIB |
| TFIIE | = | transcription factor IIE |
| Daf‐16 | = | ‘dauer’ larvae transcription factor‐16 |
| FOXO | = | forkhead box subgroup ‘O’ transcription factor |
| HML | = | homothallic mating‐type loci left |
| HMR | = | homothallic mating‐type loci right |
| NFκB | = | nuclear factor kappa B transcription factor |
| PGC‐1α | = | peroxisome proliferator‐activated receptor gamma (PPARγ) coactivator‐1α |
| Abbreviations | ||
| SIR2 | = | silent information regulator 2 |
| HAT | = | histone acetyltransferase |
| HDAC | = | histone deacetylase |
| CR | = | calorie restriction |
| PKB/AKT | = | protein kinase B |
| GDP | = | guanosine diphosphate |
| GTP | = | guanosine triphosphate |
| NAD+ | = | nicotinamide adenine dinucleotide |
| NADH | = | reduced form of NAD+ |
| Pol II | = | RNA polymerase II |
| TFIIB | = | transcription factor IIB |
| TFIIE | = | transcription factor IIE |
| Daf‐16 | = | ‘dauer’ larvae transcription factor‐16 |
| FOXO | = | forkhead box subgroup ‘O’ transcription factor |
| HML | = | homothallic mating‐type loci left |
| HMR | = | homothallic mating‐type loci right |
| NFκB | = | nuclear factor kappa B transcription factor |
| PGC‐1α | = | peroxisome proliferator‐activated receptor gamma (PPARγ) coactivator‐1α |
Acknowledgements
We thank greatly members of the Auwerx laboratory for critical reading of the manuscript and helpful discussions. This work was supported by grants of the Centre National de la Recherche Scientifique (CNRS); Institut National pour la Science et la Recherche Médicale (INSERM); National Institutes of Health (NIH); the European Union (EU) and the Hôpitaux Universitaires de Strasbourg.