Food Interactions, Sirtuins, Genes, Homeostasis, and General Discussion
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
The first role of sirtuins discovered in yeast about three decades ago is the regulation of aging and the life span extension. In addition to regulating aging, sirtuin enzymes play key roles in the maintenance of organismal metabolic homeostasis and cell survival (73–74). In mammals, sirtuins are a very complicated biological response system that influences many other regulator molecules and pathways in complex manners. Responses of this system to environmental factors, as well as its role in health and disease, are currently incompletely characterized and at most partially understood (71, 75–76). These enzymes also have primarily protective functions in the development of many age-related diseases, including cardiovascular disease, neurodegeneration, and cancer. Sirtuins regulate many fundamental biological processes such as energy metabolism and mitochondrial function in response to a variety of environmental and nutritional activators or stimuli such as vitamin B3 (niacin, nicotinamide), which is a precursor of NAD, plant polyphenols (resveratrol, quercetin, piceatannol, tannins), curcumin in turmeric, and so on (75–80). These activators are found in foods, especially plant foods, and play a key role in the activity of sirtuins which declines with age and disease. In mammals, Sirt1, its activators and inhibitors, are the best studied among all sirtuins (72).
Exercise, Metabolism and Oxidative Stress in the Epigenetic Landscape
James N. Cobley, Gareth W. Davison in Oxidative Eustress in Exercise Physiology, 2022
Histone deacetylation, on the other hand, leads to a closed chromatin configuration and gene silencing. Deacetylation reactions are metabolically responsive (Wang et al., 2018; Miranda-Goncalves et al., 2018), where the glycolytic substrate nicotinamide adenine dinucleotide (NAD) acts as a redox cofactor in the deacetylation activity of sirtuins (HDAC enzymes). There are seven sirtuins in mammalian cells, with SIRT1, 2, 6 and 7 localised to the nucleus (Miranda-Goncalves et al., 2018; Imai et al., 2000). As NAD is subject to oxidation in normal cellular metabolism, it yields NAD+ and NADH, and any adjustment in the NAD+/NADH ratio can subsequently change sirtuin activity (Figure 17.2). For instance, when cells have net positive charged (e.g. due to an increased glucose flux), the NAD+/NADH ratio drops, and this metabolic sensor inhibits sirtuin activity to regulate gene expression (Wong et al., 2017). In contrast, when cell NAD+ concentration is elevated (increased NAD+/NADH ratio), sirtuin activation occurs. So, when cells are deprived of ATP and other metabolic substrates, NAD+ levels become elevated and SIRT1, in particular, is upregulated leading to histone (H3K9ac and H3K14ac) deacetylation and a potential up-regulation of metabolic enzymes (Canto et al., 2009; Davison et al., 2021; Etchegaray and Mostoslavsky, 2016).
Aging
Shamim I. Ahmad in Aging: Exploring a Complex Phenomenon, 2017
Sirtuins are another promising agent playing a role in slowing down the aging process, thus prolonging life span with improvement in health [7]. Sirtuins were discovered in Saccharomyces cerevisiae and further studies have shown their presence from bacteria to humans [34]. In humans, the sirtuin family comprises seven members—SIRT1-7. Although sirtuins belong to the histone deacetylases class III family, they also play roles other than protein deacetylation [7]. The effect of CR increases the level of all sirtuins except SIRT-4 [35]. While SIRT-1 and SIRT-2 serve as markers of either senescence or some diseases such as cancer, diabetes, cardiovascular, and neurodegenerative disorders, SIRT-3 was found to be the only sirtuin found to influence life longevity in humans [7]. Studies have shown that SIRT-3 decreases the level of ROS in cells and increases the activity of enzymes involved in CR [36,7]. Studies have also reported the importance of SIRT-6 and 7 in life span extension. An increase in the level of SIRT-6 resulted in reduction of the insulin-like growth factor (IGF)-1 pathway, which in turn caused facilitated glucose tolerance and reduced fat accumulation as well as resulted in extended life span in mice [37].
Left ventricular hypertrophy is associated with increased sirtuin level in newly diagnosed hypertensive patients
Published in Clinical and Experimental Hypertension, 2019
Hakan Duman, Ilkay Bahçeci, Göksel Çinier, Handan Duman, Eftal Murat Bakırcı, Mustafa Çetin
The mammalian silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD) +-dependent class III histone deacetylase molecule (5). SIRT1 is the largest and best characterized Sirtuin and similar to other molecules in Sirtuin family; its activity is associated with splitting of NAD during each deacytlation cycle (6). Sirtuins can extend the lifespan by mediating beneficiary antiageing effects of low-calorie diet. Moderate SIRT1 overexpression protected mice from cardiac oxidative stress and postponed the onset of age-dependent cardiac fibrosis and cell death (7). In vitro and in vivo findings corroborated these cardio-protective effects of SIRT1 such as improvement in endothelial function, suggesting that SIRT1 activation might be of benefit for the treatment of cardiac diseases (8,9). Thus, the aim of this study was to determine the predictive role of SIRT1 as a powerful biomarker of hypertensive LVH and to explore the effects of SIRT1 on cardiac hypertrophy further.
Comparison of Calorie-Restricted Diet and Resveratrol Supplementation on Anthropometric Indices, Metabolic Parameters, and Serum Sirtuin-1 Levels in Patients With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial
Published in Journal of the American College of Nutrition, 2018
Somayyeh Asghari, Mohammad Asghari-Jafarabadi, Mohammad-Hossein Somi, Seyed-Mostafa Ghavami, Maryam Rafraf
It has been shown that adherence to low-calorie diets, weight loss, and subsequent weight maintenance had less long term success in obese participants. Therefore, recent research has focused on investigating sirtuin-activating compounds that mimic calorie-restriction effects without actually restricting caloric intake (13,18–20). In that respect, resveratrol (3,5,4-trihydroxystillbene), a natural polyphenol found in various dietary components such as grapes, berries, and peanuts, was discovered as the most potent activator of SIRT1 (21). Rodent studies have shown that resveratrol increases insulin sensitivity, improves glucose tolerance and plasma lipid levels, and prevents the development of fatty liver (22–28). In most of these studies, resveratrol induces its beneficial metabolic changes mainly through a SIRT1-dependent mechanism (8,22,28–31) and has therefore been suggested to act as a calorie-restriction mimetic (8,32).
Functional and therapeutic potential of mitochondrial SIRT3 deacetylase in disease conditions
Published in Expert Review of Clinical Pharmacology, 2018
Three members of mammalian sirtuins, i.e. SIRT3, SIRT4, and SIRT5 are localized in mitochondria. Among them, SIRT3 and SIRT5 act by deacetylating the target proteins, whereas SIRT4 shows ADP ribosyltransferase activity [9]. These mitochondrial sirtuins are actively involved in regulation of ATP synthesis, metabolism, apoptosis, and intracellular signaling [10]. SIRT3 is the most studied mitochondrial sirtuin after SIRT1. It has deacetylase activity in various metabolic processes, such as the electron transport chain (ETC), fatty acid oxidation, amino acid metabolism, redox balance, and the tricarboxylic acid cycle. SIRT3 mitochondrial substrate includes: complex I, complex III, manganese superoxide dismutase (MnSOD), and isocitrate dehydrogenase 2[11]. By deacetylating complex I and complex III, SIRT3 improves overall efficacy of the ETC by preventing production of reactive oxygen species (ROS) as oxidative phosphorylation byproducts [10,12]. On the other side, SIRT4 and SIRT5 are not yet studied thoroughly. SIRT4 has its role in citric acid cycle where it acts on glutamate dehydrogenase and malonyl-CoA decarboxylase to regulate amino acid and fatty acid utilization. SIRT5 deacetylase shows its role in regulation of pyruvate metabolism [13]. Thus, maintaining the sirtuins level is crucial for metabolic as well as physiological functions.
Related Knowledge Centers
- Ageing
- Cell Signaling
- Conserved Sequence
- In Vitro
- Protein
- Yeast
- Metabolism
- Apoptosis
- Adp-Ribosylation
- Transcription