The brain as a master regulator of body energy control. The figure represents a simplified scheme of how the brain receives signals from peripheral tissues in the hypothalamus. Orexigenic (AgRP/NPY) and anorexigenic (POMC/CART) neurons in the arcuate nucleus (ARC) of the hypothalamus sense these and other cues, such as circulating blood glucose levels. These signals are further integrated by interaction with other hypothalamic nuclei (LH—lateral hypothalamus; PVN—paraventricular nucleus) and finally project into the areas of the brain involved in the reward system, including the ventral tegmental area (VTA) and the nucleus accumbens in the striatum.

The brain as a master regulator of body energy control. The figure represents a simplified scheme of how the brain receives signals from peripheral tissues in the hypothalamus. Orexigenic (AgRP/NPY) and anorexigenic (POMC/CART) neurons in the arcuate nucleus (ARC) of the hypothalamus sense these and other cues, such as circulating blood glucose levels. These signals are further integrated by interaction with other hypothalamic nuclei (LH—lateral hypothalamus; PVN—paraventricular nucleus) and finally project into the areas of the brain involved in the reward system, including the ventral tegmental area (VTA) and the nucleus accumbens in the striatum.

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The brain has a central role in the regulation of energy stability of the organism. It is the organ with the highest energetic demands, the most susceptible to energy deficits, and is responsible for coordinating behavioral and physiological responses related to food foraging and intake. Dietary interventions have been shown to be a very effective...

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... Because energy is needed to power virtually all body functions and dietary restriction influences these functions, attention was first paid to the question: "How animals change their metabolism to meet energy demands"? The question is generally answered with a description of cooperation between organs to redirect resources to maintaining the operation of the most crucial organs needed for survival the brain (Rothman and Mattson, 2013;Amigo and Kowaltowski, 2014) and the heart (Seals et al., 2018). Operation of a variety of other functions, such as growth and reproduction, may be temporally suppressed. ...
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Intermittent fasting as a dietary intervention can prevent overweight and obesity in adult organisms. Nevertheless, information regarding consequences of intermittent fasting for redox status and reactive metabolite-mediated processes that are crucial for the normal functioning of organisms is limited. Since the information on effects of intermittent fasting on parameters of oxidative/carbonyl stress in the brains of young mice was absent, the present study addressed these questions using an every-other-day fasting (EODF) protocol. The levels of carbonyl proteins were ~28 %, 22 % and 18 % lower in the cerebral cortex of EODF males and females and middle parts of the brain of EODF males, respectively, as compared to their ad libitum fed counterparts. Lipid peroxides and α-dicarbonyl compounds were lower only in the cortex and medulla part of EODF male brain. The EODF regimen resulted in higher total non-specific antioxidant capacity in different parts of male brain and a tendency to be higher this parameter in females. At the same time, EODF regimen had no effect on the activities of the defensive antioxidant enzymes, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, glyoxylase 1 and glucose-6-phosphate dehydrogenase in the cortex of both sexes, but even decreased activities of these enzymes in medulla and middle part of the brain. In general, the results suggest that in the brain of young mice ad libitum feeding induces mild oxidative/carbonyl stress which may be partially alleviated by the EODF regimen. The effect of EODF regimen is more pronounced in the medulla part than in the cortex.
... Dietary intervention usually consists of a 20-70% reduction in diet intake without micronutrient limitation relative to an ad libitum (AL) diet. DR has been demonstrated to effectively prevent a large number of age-related neurological disorders, including learning and memory disorders (20,21). In addition to preventing age-related disease, another important property of DR is increased resistance to multiple forms of acute stress, including ischemia reperfusion injury. ...
... Reports have found that a restricted diet for 3 months to 1 year had reduced ischemic injury to the heart and brain in models of heart attack and stroke, respectively (22,23). Several neuroprotective mechanisms have been found in the beneficial effects of DR, including antioxidant effects, enhancement of autophagy, reduction of inflammation, and modulation of metabolism (19,20,24). Although the mechanisms by which DR takes its effects are still scarce, mitochondria, as master regulators of cellular metabolism, are believed to play an important role in the cellular adaptations that occurred with the diet (20,24,25). ...
... Several neuroprotective mechanisms have been found in the beneficial effects of DR, including antioxidant effects, enhancement of autophagy, reduction of inflammation, and modulation of metabolism (19,20,24). Although the mechanisms by which DR takes its effects are still scarce, mitochondria, as master regulators of cellular metabolism, are believed to play an important role in the cellular adaptations that occurred with the diet (20,24,25). However, the effects of DR on neurological injury after CA and involved mechanisms remain unknown. ...
Article
Background: Dietary restriction (DR) is a well-known intervention that increases lifespan and resistance to multiple forms of acute stress, including ischemia reperfusion injury. However, the effect of DR on neurological injury after cardiac arrest (CA) remains unknown. Methods: The effect of short-term DR (one week of 70% reduced daily diet) on neurological injury was investigated in rats using an asphyxial CA model. The survival curve was obtained using Kaplan-Meier survival analysis. Serum S-100β levels were detected by enzyme linked immunosorbent assay. Cellular apoptosis and neuronal damage were assessed by terminal deoxyribonucleotide transferase dUTP nick end labeling assay and Nissl staining. The oxidative stress was evaluated by immunohistochemical staining of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Mitochondrial biogenesis was examined by electron microscopy and mitochondrial DNA copy number determination. The protein expression was detected by western blot. The reactive oxygen species (ROS) and metabolite levels were measured by corresponding test kits. Results: Short-term DR significantly improved 3-day survival, neurologic deficit scores (NDS) and decreased serum S-100β levels after CA. Short-term DR also significantly attenuated cellular apoptosis, neuronal damage and oxidative stress in the brain after CA. In addition, short-term DR increased mitochondrial biogenesis as well as brain PGC-1α and SIRT1 protein expression after CA. Moreover, short-term DR increased adenosine triphosphate, β-hydroxybutyrate, acetyl-CoA levels and nicotinamide adenine dinucleotide (NAD+)/reduced form of NAD+ (NADH) ratios as well as decreased serum lactate levels. Conclusions: Reduction of oxidative stress, upregulation of mitochondrial biogenesis and increase of ketone body metabolism may play a crucial role in preserving neuronal function after CA under short-term DR.
... These cells also release reactive nitrogen species (RNS), radicals (nitric oxide and nitrogen dioxide), and non-radicals (peroxynitrite, dinitrogen trioxide, nitrous acid, nitroxyl anion, and nitrosyl cations), which are all neurotoxic (Sundararajan et al., 2005;Bowen et al., 2006;Kapadia et al., 2006;Satriotomo et al., 2006;Tureyen et al., 2007;Weston et al., 2007;Tang et al., 2008;Jin et al., 2010;Chu et al., 2014). Numerous studies have shown that IF before induction of stroke in rodent curtail release of ROS and RNS, as well as increase anti-oxidant defense by promoting the expression of enzymes like superoxide dismutase and catalase downstream to the transcription factor Nrf2 (Arumugam et al., 2010;Amigo and Kowaltowski, 2014;Ahn et al., 2018;Madkour et al., 2019). Fasting is known to cause metabolic switching resulting in lowered glucose and increased fatty acid use for energy production. ...
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Diet is a significant factor in determining human well-being. Excessive eating and/or diets with higher than needed amounts of carbohydrates, salt, and fat are known to cause metabolic disorders and functional changes in the body. To compensate the ill effects, many designer diets including the Mediterranean diet, the Okinawa diet, vegetarian/vegan diets, keto diet, anti-inflammatory diet, and the anti-oxidant diet have been introduced in the past 2 decades. While these diets are either enriched or devoid of one or more specific components, a better way to control diet is to limit the amount of food consumed. Caloric restriction (CR), which involves limiting the amount of food consumed rather than eliminating any specific type of food, as well as intermittent fasting (IF), which entails limiting the time during which food can be consumed on a given day, have gained popularity because of their positive effects on human health. While the molecular mechanisms of these 2 dietary regimens have not been fully deciphered, they are known to prolong the life span, control blood pressure, and blood glucose levels. Furthermore, CR and IF were both shown to decrease the incidence of heart attack and stroke, as well as their ill effects. In particular, IF is thought to promote metabolic switching by altering gene expression profiles leading to reduced inflammation and oxidative stress, while increasing plasticity and regeneration.
... In addition, SIRT2 deacetylates p65 at Lys310, regulating the expression of NF-κB-related genes (Deeb et al., 2010). Therefore, SIRT2 could promote inflammation and neuronal cell death by activating transcription of NF-κB (Amigo and Kowaltowski, 2014). The effect of SIRT2 on the survival of microglia under resting and activated conditions is unclear. ...
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Parkinson’s disease (PD), the main risk factor of which is age, is one of the most common neurodegenerative diseases, thus presenting a substantial burden on the health of affected individuals as well as an economic burden. Sirtuin 2 (SIRT2), a subtype in the family of sirtuins, belongs to class III histone deacetylases (HDACs). It is known that SIRT2 levels increase with aging, and a growing body of evidence has been accumulating, showing that the activity of SIRT2 mediates various processes involved in PD pathogenesis, including aggregation of α-synuclein (α-syn), microtubule function, oxidative stress, inflammation, and autophagy. There have been conflicting reports about the role of SIRT2 in PD, in that some studies indicate its potential to induce the death of dopaminergic (DA) neurons, and that inhibition of SIRT2 may, therefore, have protective effects in PD. Other studies suggest a protective role of SIRT2 in the context of neuronal damage. As current treatments for PD are directed at alleviating symptoms and are very limited, a comprehensive understanding of the enzymology of SIRT2 in PD may be essential for developing novel therapeutic agents for the treatment of this disease. This review article will provide an update on our knowledge of the structure, distribution, and biological characteristics of SIRT2, and highlight its role in the pathogenesis of PD.
... Another study in this regard indicated that IF may be involved in the improvement of neural survival from oxidative stress in the rodent model of cerebral ischemia either by increasing the antioxidant effects or reducing the reactive oxygen species and providing mitochondrial protection in the brain [26]. Similarly, a study demonstrated that IF could also improve neural survival from inflammation in the rodent model of cerebral ischemia through multiple pathways either by the reduction of pro-inflammatory genes or eliminating inflammatory stimuli from the brain [27]. ...
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Ramadan is the Holy month of fasting that is obligatory for all normal Muslims who reached at their puberty. Two meals are taken during Ramadan, one is taken before down to prepare themselves for fast is called “Sahur”, and second meal is taken at sunset is called “Iftar”. Fasting is not only a ritual and religious obligation while it has several medicinal significances specially against diet dependent diseases. Fasting significantly helped in the reduction of peptic and duodenal ulcers with the combination of H2-blocker drug, help in the improvement of lipid profile specially in TC and HDL and LDL levels that cause heart failure. During fasting the systolic and diastolic blood pressure improve at greater rate as compare to drugs like Indapamide and Perindopril, a strong evidence revealed that ischemic stroke and cancer can also be improved by intermitted fasting through multiple pathways and factors like BDNF, bFGF, GRP78, Hsp70, tyrosine kinase receptor B (TrkB), fibroblast growth factor receptor 1 (FGFR1), and ketosis respectively The aim of this paper is to systematically review the published literature regarding the effect of Ramadan on the above mentioned diseases.
... Several studies have shown that DR exerts antiinflammatory role by altering the level of circulating leptin and ghrelin resulting in enhanced production of NPY [44À46]. DR is reported to induce metabolic reprogramming by activation of SIRT1 which regulates oxidation of fatty acids in liver and mobilization of lipids in adipose tissue [47]. DR has been reported to induce SIRT1 expression and mitochondrial biogenesis through SIRT1-mediated deacetylation of PGC-1α, a major regulator of biogenesis. ...
... Benefits of CR have been linked to rodent models of age-related neurological disorders [108]. This has been shown by CR assays in SAMP8 mice, a model of pathological accelerated aging. ...
Chapter
Bioenergetic homeostasis is a vital process maintaining cellular health and has primary importance in neuronal cells due to their high energy demand markedly at synapses. Mitochondria, the metabolic hubs of the cells, are the organelles responsible for producing energy in the form of ATP by using nutrients and oxygen. Defects in mitochondrial homeostasis result in energy deprivation and can lead to disrupted neuronal functions. Mitochondrial defects adversely contribute to the pathogenesis of neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s disease (PD). Mitochondrial defects not only include reduced ATP levels but also increased reactive oxygen species (ROS) leading to cellular damage. Here, we detail the mechanisms that lead to neuronal pathologies involving mitochondrial defects. Furthermore, we discuss how to target these mitochondrial defects in order to have beneficial effects as novel and complementary therapeutic avenues in neurodegenerative diseases. The critical evaluation of these strategies and their potential outcome can pave the way for finding novel therapies for neurodegenerative pathologies.
... Sirtuin-1 is largely localized in the nucleus and, to a lesser extent, in the cytoplasm. It is most closely associated with mechanisms involved in aging and longevity, by deacetylating the main regulator of biogenesis PGC-1α and transcriptional FoxO factor (53). FoxO proteins are capable of increasing longevity by ensuring resistance to oxidative stress, protecting protein structures and promoting lipid metabolism and autophagy (15). ...
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One of the key mechanisms of the aging process of an organism and of the dysfunctionality and chronic diseases related with aging is the so-called cell senescence. It implies irreversible cell cycle arrest that occurs in response to different forms of cellular stress. Senescent cells that accumulate over time are viable, subject to phenotypic changes and excrete different soluble factors, and may affect adjacent cells, resulting in tissue and organ function disorders.Since old age is an important risk factor for many diseases, the interest of the scientific community is to reduce or avoid the effects of the aging processes. Among numerous developed therapeutic strat-egies, the development of senotherapeutics (i.e. the targeting strategy) has a significant place and is based on the removal of senescent cells and the abolishment of their adverse effects. Although many questions are still open, based on numerous experimental studies, it is expected that the development of senotherapeutics will contribute to the healthy life of the elderly and the treatment of specific age-related diseases.
... Sirtuins are nicotinamide adenine dinucleotide (NAD+) dependent enzymes (Herskovits and Guarente, 2013). In terms of their evolution, they are highly conserved proteins in both prokaryotes and eukaryotes (Amigo and Kowaltowski, 2014). This family of proteins shares a similar enzymatic domain of approximately 250 amino acids. ...
Article
Sirtuins are NAD+-dependent enzymes that regulate a large number of cellular pathways and are related to aging and age-associated diseases. In recent years, the role of sirtuins in Alzheimer's disease (AD) has become increasingly apparent. Growing evidence demonstrates that sirtuin 1 (SIRT1) regulates many processes that go amiss in AD, such as: APP processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. Here we review how SIRT1 affects AD and cognition, the main mechanisms in which SIRT1 is related to AD pathology, and its importance for the prevention and possible diagnosis of AD.
... The cellular and molecular mechanisms by which dietary restriction enhances brain plasticity and improves cognitive functions during aging include increase in synaptic activity that causes production of neurotrophic factors (Amigo and Kowaltowski 2014), which in turn, stimulate the formation of new synapses and promote neurogenesis and potentiation (Anton and Leeuwenburgh 2013). Other factors include activation of cellular stress-responsive machinery against oxidative and metabolic stress (Bruce-Keller et al. 1999), and activation of immune and inflammatory mediators (reviewed in Mattson 2015). ...
... Sirtuins are family of NAD + -dependent mitochondrial deacetylases, which monitor oxidative and energy metabolism along with mitochondrial dynamics within mitochondrial matrix and maintain cellular homeostasis (Tang et al. 2017;Su et al. 2017). Dietary restriction has been reported to enhance SIRT1 expression and mitochondrial biogenesis through SIRT-1-mediated deacetylation of PGC-1α, a major regulator of biogenesis (Amigo and Kowaltowski 2014;Cohen et al. 2004;Nemoto et al. 2005). SIRT1 orchestrates oxidation of fatty acids in the muscle and liver and mobilization of lipid in adipose tissue, thus suggesting that its activation in dietary restriction may induce metabolic reprogramming (Rodgers et al. 2005;Fiskum et al. 2008;Amigo and Kowaltowski 2014). ...
... Dietary restriction has been reported to enhance SIRT1 expression and mitochondrial biogenesis through SIRT-1-mediated deacetylation of PGC-1α, a major regulator of biogenesis (Amigo and Kowaltowski 2014;Cohen et al. 2004;Nemoto et al. 2005). SIRT1 orchestrates oxidation of fatty acids in the muscle and liver and mobilization of lipid in adipose tissue, thus suggesting that its activation in dietary restriction may induce metabolic reprogramming (Rodgers et al. 2005;Fiskum et al. 2008;Amigo and Kowaltowski 2014). In yeast, protein Sir2, a gene product of SIR2, catalyzes histone deacetylation and NAD + cleavage. ...
Chapter
Old age is one of the major determinants of neurodegenerative diseases. There have been major advancements in understanding the biology of aging along with various interventions that may promote healthy aging. Many nutritional interventions such as caloric restriction, periodic fasting, and alternate day fasting have been proposed that may hamper age-associated cognitive decline. Among the various regimens, intermittent fasting-dietary restriction (IF-DR) seems to be most promising as it has been well documented to provide neuroprotection by enhancing synaptic plasticity and neurogenesis. It is also known to prolong life span and delay the onset of age-associated disorders by reducing inflammation and oxidative stress. IF-DR regimen is known to possibly work by establishing a conditioning response which maintains survival mode in organisms by focusing on energy conservation, thereby causing a metabolic shift from growth to maintenance activities and hence promoting anti-aging effects. IF-DR regimen is also known to improve many physiological indicators such as reduced levels of leptin, insulin, amount of body fat, reduced blood pressure, and increase in resistance to stress. Thus, IF-DR regimen initiated in middle or old age has the ability to impede age-associated neurodegeneration and cognitive decline and may be a potential intervention to abrogate age-related impairment of brain functions.