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      Caloric restriction reduces the systemic progression of mouse AApoAII amyloidosis

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          Abstract

          In mouse senile amyloidosis, apolipoprotein (Apo) A-II is deposited extracellularly in many organs in the form of amyloid fibrils (AApoAII). Reduction of caloric intake, known as caloric restriction (CR), slows the progress of senescence and age-related disorders in mice. In this study, we intravenously injected 1 μg of isolated AApoAII fibrils into R1.P1- Apoa2c mice to induce experimental amyloidosis and investigated the effects of CR for the next 16 weeks. In the CR group, AApoAII amyloid deposits in the liver, tongue, small intestine and skin were significantly reduced compared to those of the ad libitum feeding group. CR treatment led to obvious reduction in body weight, improvement in glucose metabolism and reduction in the plasma concentration of ApoA-II. Our molecular biological analyses of the liver suggested that CR treatment might improve the symptoms of inflammation, the unfolded protein response induced by amyloid deposits and oxidative stress. Furthermore, we suggest that CR treatment might improve mitochondrial functions via the sirtuin 1-peroxisome proliferator-activated receptor γ coactivator 1α (SIRT1-PGC-1α) pathway. We suggest that CR is a promising approach for treating the onset and/or progression of amyloidosis, especially for systemic amyloidosis such as senile AApoAII amyloidosis. Our analysis of CR treatment for amyloidosis should provide useful information for determining the cause of amyloidosis and developing effective preventive treatments.

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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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            Eating oneself and uninvited guests: autophagy-related pathways in cellular defense.

            The eukaryotic cell uses an evolutionarily conserved lysosomal pathway of self-digestion (autophagy) for survival when extracellular nutrients are limited. In this issue of Cell, new evidence indicates that autophagy is used to for survival when intracellular nutrients are limited by growth factor deprivation (Lum et al., 2005). Other recent studies indicate that the autophagy machinery is also used to degrade foreign microbial invaders (xenophagy).
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              Essential role for autophagy in life span extension.

              Life and health span can be prolonged by calorie limitation or by pharmacologic agents that mimic the effects of caloric restriction. Both starvation and the genetic inactivation of nutrient signaling converge on the induction of autophagy, a cytoplasmic recycling process that counteracts the age-associated accumulation of damaged organelles and proteins as it improves the metabolic fitness of cells. Here we review experimental findings indicating that inhibition of the major nutrient and growth-related signaling pathways as well as the upregulation of anti-aging pathways mediate life span extension via the induction of autophagy. Furthermore, we discuss mounting evidence suggesting that autophagy is not only necessary but, at least in some cases, also sufficient for increasing longevity.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 February 2017
                2017
                : 12
                : 2
                : e0172402
                Affiliations
                [1 ]Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Matsumoto, Japan
                [2 ]Department of Biological Sciences for Intractable Neurological Diseases, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Japan
                [3 ]Department of Advanced Medicine for Health Promotion, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Japan
                Universita degli Studi di Padova, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: JS KH.

                • Formal analysis: JS HM.

                • Funding acquisition: JS KH.

                • Investigation: LL JS XD MY ZX HM.

                • Methodology: LL JS KH.

                • Project administration: JS KH.

                • Resources: LL JS MM KH.

                • Software: HM.

                • Supervision: JS KH.

                • Validation: JS.

                • Visualization: LL JS.

                • Writing – original draft: LL JS KH.

                • Writing – review & editing: JS KH.

                Article
                PONE-D-16-26155
                10.1371/journal.pone.0172402
                5321440
                28225824
                91baca49-5294-48f0-8c2d-23b46e404f08
                © 2017 Li et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 June 2016
                : 22 November 2016
                Page count
                Figures: 5, Tables: 0, Pages: 20
                Funding
                Funded by: the Ministry of Education, Culture, Sports, Science, and Technology of Japan
                Award ID: Scientific Research (B) (23390093 and 26293084)
                Funded by: the Ministry of Education, Culture, Sports, Science, and Technology of Japan
                Award ID: Scientific Research (C) (24500849)
                Award Recipient :
                Funded by: the Ministry of Education, Culture, Sports, Science, and Technology of Japan
                Award ID: Challenging Exploratory Research (26670152)
                Funded by: the Intractable Disease Division, the Ministry of Health, Labor, and Welfare to the Research Committees for Amyloidosis
                This research was supported by Grants-in-Aid for Scientific Research (B) (23390093 and 26293084) (KH), Scientific Research (C)(24500849) (JS), and Challenging Exploratory Research (26670152) (KH) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by grants (KH) from the Intractable Disease Division, the Ministry of Health, Labor, and Welfare to the Research Committees for Amyloidosis, Japan.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Amyloidosis
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Amyloidosis
                Biology and Life Sciences
                Biochemistry
                Proteins
                Amyloid Proteins
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                Anatomy
                Body Fluids
                Blood
                Blood Plasma
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                Anatomy
                Body Fluids
                Blood
                Blood Plasma
                Biology and Life Sciences
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                Body Fluids
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                Biology and Life Sciences
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                Mitochondria
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                Cell Biology
                Cellular Structures and Organelles
                Energy-Producing Organelles
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                Biochemistry
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                Plasma Proteins
                Biology and Life Sciences
                Immunology
                Immune Response
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