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Food Interactions, Sirtuins, Genes, Homeostasis, and General Discussion
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
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
Published in James N. Cobley, Gareth W. Davison, Oxidative Eustress in Exercise Physiology, 2022
Gareth W. Davison, Colum P. Walsh
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).
Energy Metabolism, Metabolic Sensors, and Nutritional Interventions in Polycystic Kidney Disease
Published in Jinghua Hu, Yong Yu, Polycystic Kidney Disease, 2019
Sonu Kashyap, Eduardo Nunes Chini
The NAD+-dependent deacetylase SIRT1 is the most extensively studied member of the sirtuins family which serves as a metabolic master switch that is part of several physiological pathways.41,42 SIRT1 uses NAD+ as a substrate to promote deacetylation of target proteins affecting several cellular processes.43–45 Sirtuins play an important role in several diseases, specifically those with alterations in metabolism and stress response. Activation of SIRT1 has shown protection against liver steatosis, type II diabetes, and cancer and also has been shown to delay some features of aging.42–44,46 Although debated, the beneficial effects of dietary interventions might be mediated by SIRT1.42–44
The Protective Activity of Penehyclidine Hydrochloride against Renal Ischemia/Reperfusion-Mediated NLRP3 Inflammasome Activation is Induced by SIRT1
Published in Journal of Investigative Surgery, 2022
Zhaohui Liu, Yanli Meng, Qianjie Wei, Yu Miao, Lili Yu, Yuqing Li, Bing Zhang
Recent studies have shown that an inflammatory response-related multiprotein complex (inflammasome) plays a key role in AM-induced innate immunity [12, 13]. Several inflammasomes, including pyrin domain-containing protein 1 (NLRP1), NLRP2, NLRP3, absent in melanoma 2 (AIM2), and ice protease-activating factor (IPAF), have been identified [14]. Of these, NLRP3 has been extensively studied— it plays a crucial role in inflammatory cytokines production and inflammation response [15]. Reportedly, the cleavage of procaspase-1 into caspase-1 activates the NLRP3 inflammasome and induces the production of proinflammatory cytokines such as interleukin (IL)-1β and IL-18 [15]. In AMs, rI/R promotes the IL-1β and NLRP3 inflammasome production [11]. The sirtuin family of proteins comprising seven proteins plays important roles in the cellular response to metabolic, inflammatory, and oxidative stressors [16]. It has been shown that sirtuin 1 (SIRT1), a member of the sirtuin family of proteins, plays an important role in cellular inflammation regulation [17]. Several studies have shown that SIRT1 mediates the inflammatory response by regulating the activation of the NLRP3 inflammasome [18]. For example, Peng et al. demonstrated that the high activity of SIRT1 decreases the NLRP3 inflammasome activation [19]. Wang et al. have shown that in vascular endothelial cells, SIRT1 inhibits inflammatory response partly through the regulation of NLRP3 inflammasome [20].
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.
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.