Sirtuins as regulators of metabolism and healthspan

By R. Houtkooper, E. Pirinen, Johan Auwerx. Nature reviews. Molecular cell biology, 2012

1,942 citations recorded by the source corpus.

Since the beginning of the century, the mammalian sirtuin protein family (comprising SIRT1–SIRT7) has received much attention for its regulatory role, mainly in metabolism and ageing. Sirtuins act in different cellular compartments: they deacetylate histones and several transcriptional regulators in the nucleus, but also specific proteins in other cellular compartments, such as in the cytoplasm and in mitochondria. As a consequence, sirtuins regulate fat and glucose metabolism in response to physiological changes in energy levels, thereby acting as crucial regulators of the network that controls energy homeostasis and as such determines healthspan.

Subfields: Geriatrics and Gerontology, Physiology

View Paper: https://www.semanticscholar.org/paper/24a21c4578cb1ca515403a621d16df8116ae52b4

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Citations in the corpus

Histone Modifications and Cancer. (2016, background): “…et al. 2012) and hepatoceullar cancer; higher levels associated with node-positive breast cancer Adapted from Witt et al. 2009; Bosch-Presegue and Vaquero 2011; Stunkel and Campbell 2011; Barneda-Zahonero and Parra 2012; Houtkooper et al. 2012; Bernt 2013; Gong and Miller 2013; Paredes et al. 2014.”
Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents (2015, background): “Sirtuins have emerged as potential therapeutic targets for the treatment of various diseases, such as cancer, cardiovascular, aging and neurodegenerative related diseases [16–19].”
NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus (2015, background): “For further information, we refer the reader to recent specialized reviews (Boutant and Canto, 2014; Chang and Guarente, 2013; Houtkooper et al., 2012).”
Acetyl coenzyme A: a central metabolite and second messenger. (2015, background): “Along similar lines, L-carnitine and sphingosine-1-phosphate favor histone acetylation by operating as HDAC1 and HDAC2 inhibitors (Hait et al., 2009; Huang et al., 2012).”
The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling (2013, neutral): “1 and involve the induction of mitonuclear protein imbalance as well as activation of stress signaling via the mitochondrial unfolded protein response (UPRmt) and the nuclear translocation and activation of FOXO transcription factor DAF-16.”
Acetyl-CoA and the Regulation of Metabolism: Mechanisms and Consequences (2015, background): “The dependency of sirtuins on NAD+ have led to the hypothesis that their activity could be regulated by fluctuations in NAD+ concentrations [63,64].”
Mechanisms of Hepatic Triglyceride Accumulation in Nonalcoholic Fatty Liver Disease (2013, neutral): “Accumulating evidence also indicates that members of the sirtuin gene family, especially SIRT1 and SIRT3, play important roles in fatty acid oxidation during conditions of caloric deprivation [52].”
The Role of Sirtuins in Antioxidant and Redox Signaling (2017, background): “Due to the essential roles SIRT6 has in cellular homeostasis, disruption of this enzyme appears to produce an effect on disease development (12, 53, 57, 101, 136, 161).”
Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression (2015, background): “The mitochondrial deacetylase SIRT3 also promotes mitochondrial metabolism by deacetylating and activating enzymes involved in the TCA cycle and fatty acid oxidation [26].”
NAD+ Biosynthesis and Signaling in Plants (2018, background): “The most studied belong to the class I (Houtkooper et al., 2012), those of class II contain an additional ADP ribosyltransferase activity, whilst the mammalian SIRT4 activity regulates mitochondrial glutamate dehydrogenase (GDH, EC 1.”
Senescence and aging: Causes, consequences, and therapeutic avenues (2018, background): “Sirtuins are ribosyltransferases with a wide array of functions, such as metabolism regulation and DNA repair (Houtkooper et al., 2012).”