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      Protein Restriction, Epigenetic Diet, Intermittent Fasting as New Approaches for Preventing Age-associated Diseases

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          Abstract

          Data from epidemiological and experimental studies have shown that diet and eating patterns have a major role in the pathogenesis of many age-associated diseases. Since 1935, calorie restriction (CR) has been identified as one of the most effective nongenetic dietary interventions that can increase lifespan. It involves reducing calorie intake by about 20%–40% below ad libitum, without malnutrition. Restricting food intake has been observed to increase lifespan and prevent many age-associated diseases in rats, mice, and many other species. Understanding the metabolic, molecular, and cellular mechanisms involved in the anti-aging effects of CR can help us to find dietary interventions that can mimic its effects. Recently, different studies have shown that intermittent fasting, protein restriction, and an epigenetic diet can have similar effects to those of CR. These approaches were selected because it has been indicated that they act through a similar molecular pathway and also, are safe and effective in delaying or preventing diseases. In this review, we focus on the mechanistic pathway involved in CR. Then, we review the mimicking interventions through the mechanistic approach. For this purpose, we reviewed both animal and human articles, mainly available through the PubMed online database. We then selected the most relevant full texts which are summarized in this article.

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          Most cited references 64

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          Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction.

          Sir2 is an NAD-dependent deacetylase that connects metabolism with longevity in yeast, worms and flies. Mammals contain seven homologs of yeast Sir2, SIRT1-7. Here, we review recent findings demonstrating the role of these mammalian sirtuins as regulators of physiology, calorie restriction, and aging. The current findings sharpen our understanding of sirtuins as potential pharmacological targets to treat the major diseases of aging.
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            Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study.

            Calorie restriction (CR), a reduction of 10–40% in intake of a nutritious diet, is often reported as the most robust non-genetic mechanism to extend lifespan and healthspan. CR is frequently used as a tool to understand mechanisms behind ageing and age-associated diseases. In addition to and independently of increasing lifespan, CR has been reported to delay or prevent the occurrence of many chronic diseases in a variety of animals. Beneficial effects of CR on outcomes such as immune function, motor coordination and resistance to sarcopenia in rhesus monkeys have recently been reported. We report here that a CR regimen implemented in young and older age rhesus monkeys at the National Institute on Aging (NIA) has not improved survival outcomes. Our findings contrast with an ongoing study at the Wisconsin National Primate Research Center (WNPRC), which reported improved survival associated with 30% CR initiated in adult rhesus monkeys (7–14 years) and a preliminary report with a small number of CR monkeys. Over the years, both NIA and WNPRC have extensively documented beneficial health effects of CR in these two apparently parallel studies. The implications of the WNPRC findings were important as they extended CR findings beyond the laboratory rodent and to a long-lived primate. Our study suggests a separation between health effects, morbidity and mortality, and similar to what has been shown in rodents, study design, husbandry and diet composition may strongly affect the life-prolonging effect of CR in a long-lived nonhuman primate.
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              Overview of caloric restriction and ageing.

               E Masoro (2005)
              It has been known for some 70 years that restricting the food intake of laboratory rats extends their mean and maximum life span. In addition, such life extension has been observed over the years in many other species, including mice, hamsters, dogs, fish, invertebrate animals, and yeast. Since this life-extending action appears to be due to a restricted intake of energy, this dietary manipulation is referred to as caloric restriction (CR). CR extends life by slowing and/or delaying the ageing processes. The underlying biological mechanism responsible for the life extension is still not known, although many hypotheses have been proposed. The Growth Retardation Hypothesis, the first proposed, has been tested and found wanting. Although there is strong evidence against the Reduction of Body Fat Hypothesis, efforts have recently been made to resurrect it. While the Reduction of Metabolic Rate Hypothesis is not supported by experimental findings, it nevertheless still has advocates. Currently, the most popular concept is the Oxidative Damage Attenuation Hypothesis; the results of several studies provide support for this hypothesis, while those of other studies do not. The Altered Glucose-Insulin System Hypothesis and the Alteration of the Growth Hormone-IGF-1 Axis Hypothesis have been gaining favor, and data have emerged that link these two hypotheses as one. Thus, it may now be more appropriate to refer to them as the Attenuation of Insulin-Like Signaling Hypothesis. Finally, the Hormesis Hypothesis may provide an overarching concept that embraces several of the other hypotheses as merely specific examples of hormetic processes. For example, the Oxidative Damage Attenuation Hypothesis probably addresses only one of likely many damaging processes that underlie aging. It is proposed that low-intensity stressors, such as CR, activate ancient hormetic defense mechanisms in organisms ranging from yeast to mammals, defending them against a variety of adversities and, when long-term, retarding senescent processes.
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                Author and article information

                Journal
                Int J Prev Med
                Int J Prev Med
                IJPVM
                International Journal of Preventive Medicine
                Medknow Publications & Media Pvt Ltd (India )
                2008-7802
                2008-8213
                2018
                29 June 2018
                : 9
                Affiliations
                Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
                Author notes
                Address for correspondence: Prof. Mohammadreza Vafa, School of Public Health, Iran University of Medical Sciences, Tehran, Iran. E-mail: vafa.m@ 123456iums.ac.ir
                Article
                IJPVM-9-58
                10.4103/ijpvm.IJPVM_397_16
                6036773
                Copyright: © 2018 International Journal of Preventive Medicine

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

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