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      Polyphenols as Caloric-Restriction Mimetics and Autophagy Inducers in Aging Research

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          Abstract

          It has been thought that caloric restriction favors longevity and healthy aging where autophagy plays a vital role. However, autophagy decreases during aging and that can lead to the development of aging-associated diseases such as cancer, diabetes, neurodegeneration, etc. It was shown that autophagy can be induced by mechanical or chemical stress. In this regard, various pharmacological compounds were proposed, including natural polyphenols. Apart from the ability to induce autophagy, polyphenols, such as resveratrol, are capable of modulating the expression of pro- and anti-apoptotic factors, neutralizing free radical species, affecting mitochondrial functions, chelating redox-active transition metal ions, and preventing protein aggregation. Moreover, polyphenols have advantages compared to chemical inducers of autophagy due to their intrinsic natural bio-compatibility and safety. In this context, polyphenols can be considered as a potential therapeutic tool for healthy aging either as a part of a diet or as separate compounds (supplements). This review discusses the epigenetic aspect and the underlying molecular mechanism of polyphenols as an anti-aging remedy. In addition, the recent advances of studies on NAD-dependent deacetylase sirtuin-1 (SIRT1) regulation of autophagy, the role of senescence-associated secretory phenotype (SASP) in cells senescence and their regulation by polyphenols have been highlighted as well. Apart from that, the review also revised the latest information on how polyphenols can help to improve mitochondrial function and modulate apoptosis (programmed cell death).

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          Most cited references281

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          Cell death: a review of the major forms of apoptosis, necrosis and autophagy

          Cell death was once believed to be the result of one of two distinct processes, apoptosis (also known as programmed cell death) or necrosis (uncontrolled cell death); in recent years, however, several other forms of cell death have been discovered highlighting that a cell can die via a number of differing pathways. Apoptosis is characterised by a number of characteristic morphological changes in the structure of the cell, together with a number of enzyme-dependent biochemical processes. The result being the clearance of cells from the body, with minimal damage to surrounding tissues. Necrosis, however, is generally characterised to be the uncontrolled death of the cell, usually following a severe insult, resulting in spillage of the contents of the cell into surrounding tissues and subsequent damage thereof. Failure of apoptosis and the resultant accumulation of damaged cells in the body can result in various forms of cancer. An understanding of the pathways is therefore important in developing efficient chemotherapeutics. It has recently become clear that there exists a number of subtypes of apoptosis and that there is an overlap between apoptosis, necrosis and autophagy. The goal of this review is to provide a general overview of the current knowledge relating to the various forms of cell death, including apoptosis, necrosis, oncosis, pyroptosis and autophagy. This will provide researchers with a summary of the major forms of cell death and allow them to compare and contrast between them.
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            Mammalian sirtuins: biological insights and disease relevance.

            Aging is accompanied by a decline in the healthy function of multiple organ systems, leading to increased incidence and mortality from diseases such as type II diabetes mellitus, neurodegenerative diseases, cancer, and cardiovascular disease. Historically, researchers have focused on investigating individual pathways in isolated organs as a strategy to identify the root cause of a disease, with hopes of designing better drugs. Studies of aging in yeast led to the discovery of a family of conserved enzymes known as the sirtuins, which affect multiple pathways that increase the life span and the overall health of organisms. Since the discovery of the first known mammalian sirtuin, SIRT1, 10 years ago, there have been major advances in our understanding of the enzymology of sirtuins, their regulation, and their ability to broadly improve mammalian physiology and health span. This review summarizes and discusses the advances of the past decade and the challenges that will confront the field in the coming years.
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              MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation.

              The TOR (target of rapamycin) kinase limits longevity by poorly understood mechanisms. Rapamycin suppresses the mammalian TORC1 complex, which regulates translation, and extends lifespan in diverse species, including mice. We show that rapamycin selectively blunts the pro-inflammatory phenotype of senescent cells. Cellular senescence suppresses cancer by preventing cell proliferation. However, as senescent cells accumulate with age, the senescence-associated secretory phenotype (SASP) can disrupt tissues and contribute to age-related pathologies, including cancer. MTOR inhibition suppressed the secretion of inflammatory cytokines by senescent cells. Rapamycin reduced IL6 and other cytokine mRNA levels, but selectively suppressed translation of the membrane-bound cytokine IL1A. Reduced IL1A diminished NF-κB transcriptional activity, which controls much of the SASP; exogenous IL1A restored IL6 secretion to rapamycin-treated cells. Importantly, rapamycin suppressed the ability of senescent fibroblasts to stimulate prostate tumour growth in mice. Thus, rapamycin might ameliorate age-related pathologies, including late-life cancer, by suppressing senescence-associated inflammation.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                08 May 2020
                May 2020
                : 12
                : 5
                : 1344
                Affiliations
                [1 ]Research Institute of Fundamental and Applied Medicine named after B. Atchabarov, S.D. Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan; yessenkyzy.a@ 123456gmail.com (A.Y.); talgat-nur@ 123456mail.ru (T.N.)
                [2 ]Department of Human Anatomy, NSC “Medical University of Astana”, Nur-Sultan 010000, Kazakhstan; Marinazhmk@ 123456mail.ru
                [3 ]Department of Biological Sciences, Louisiana Tech University, Ruston, LA 71270, USA; ama083@ 123456latech.edu
                [4 ]National Laboratory Astana, Nazarbayev University, Nur-Sultan 010000, Kazakhstan; bauyrzhan.umbayev@ 123456nu.edu.kz (B.U.); shynggys.sergazy@ 123456gmail.com (S.S.); akin@ 123456mail.ru (A.G.)
                [5 ]Khanty-Mansiysk State Medical Academy, Tyumen Region, Khanty-Mansiysk Autonomous Okrug—Ugra, Khanty-Mansiysk 125438, Russia; KrivyhEA@ 123456hmgma.ru
                Author notes
                [* ]Correspondence: tim.saliev@ 123456gmail.com ; Tel.: +7-(727)-338-7225
                Author information
                https://orcid.org/0000-0001-5696-6363
                https://orcid.org/0000-0002-0286-7252
                https://orcid.org/0000-0002-6030-620X
                Article
                nutrients-12-01344
                10.3390/nu12051344
                7285205
                32397145
                ba209a52-d551-4ac4-8fe7-7460c226f088
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 March 2020
                : 16 April 2020
                Categories
                Review

                Nutrition & Dietetics
                polyphenols,caloric-restriction mimetics,autophagy,aging,apoptosis
                Nutrition & Dietetics
                polyphenols, caloric-restriction mimetics, autophagy, aging, apoptosis

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