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      Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates

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          Abstract

          The health benefits of chronic caloric restriction resulting in lifespan extension are well established in many short-lived species, but the effects in humans and other primates remain controversial. Here we report the most advanced survival data and the associated follow-up to our knowledge of age-related alterations in a cohort of grey mouse lemurs ( Microcebus murinus, lemurid primate) exposed to a chronic moderate (30%) caloric restriction. Compared to control animals, caloric restriction extended lifespan by 50% (from 6.4 to 9.6 years, median survival), reduced aging-associated diseases and preserved loss of brain white matter in several brain regions. However, caloric restriction accelerated loss of grey matter throughout much of the cerebrum. Cognitive and behavioural performances were, however, not modulated by caloric restriction. Thus chronic moderate caloric restriction can extend lifespan and enhance health of a primate, but it affects brain grey matter integrity without affecting cognitive performances.

          Abstract

          Fabien Pifferi et al. report survival and age-related brain atrophy data in grey mouse lemurs fed either a normal diet or a diet restricted in calories by 30%. They find that caloric restriction extended life span by 50% and decelerated brain white matter atrophy, but accelerated the loss of grey matter, in most of the cerebrum.

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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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            Caloric restriction improves health and survival of rhesus monkeys

            Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health.
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              The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size

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                Author and article information

                Contributors
                fabienne.aujard@mnhn.fr
                Journal
                Commun Biol
                Commun Biol
                Communications Biology
                Nature Publishing Group UK (London )
                2399-3642
                5 April 2018
                5 April 2018
                2018
                : 1
                : 30
                Affiliations
                [1 ]ISNI 0000 0000 8585 8962, GRID grid.464161.0, UMR CNRS/MNHN 7179, , Mécanismes Adaptatifs et Evolution, ; 1 Avenue du Petit Château, 91800 Brunoy, France
                [2 ]ISNI 0000 0001 2149 7878, GRID grid.410511.0, Unité d’ Ophtalmologie, , Université Paris-Est, Ecole Nationale Vétérinaire d’Alfort, ; 7 Avenue du Général de Gaulle, 94704 Maisons-Alfort, France
                [3 ]Histology and Pathology Department, Veterinary School of Alfort, PRES Paris Est, 94704 Maisons-Alfort, France
                [4 ]ISNI 0000 0001 2169 3027, GRID grid.428547.8, Service de Biostatistique et d’Épidémiologie Clinique, , Ecole Nationale Vétérinaire d’Alfort, ; Maisons-Alfort, 94704 France
                [5 ]ISNI 0000 0000 9909 5847, GRID grid.462076.1, Université de Strasbourg, IPHC, ; 23 rue Becquerel, 67087 Strasbourg, France
                [6 ]ISNI 0000 0001 2112 9282, GRID grid.4444.0, CNRS, UMR7178, ; 23 rue Becquerel, 67087 Strasbourg, France
                [7 ]ISNI 0000 0001 2188 0914, GRID grid.10992.33, Unité Mixte de Recherche en Santé 894 INSERM, Centre de Psychiatrie et Neurosciences, , Université Paris Descartes, Sorbonne Paris Cité, ; 102-108 rue de la Santé, Paris, 75014 France
                [8 ]Laboratoire de Psychopathologie et de Neuropsychologie, EA 2027, Université Paris 8, 2 rue de la Liberté, 93000 St Denis, France
                [9 ]GRID grid.457349.8, Neurodegenerative Diseases Laboratory, , CNRS, CEA, Université Paris-Sud, Université Paris-Saclay UMR 9199, ; 92265 Fontenay-aux-Roses, France
                [10 ]Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA), Direction de la Recherche Fondamentale (DRF), Molecular Imaging Research Center (MIRCen), 92265 Fontenay-aux-Roses, France
                Author information
                http://orcid.org/0000-0001-8838-0762
                http://orcid.org/0000-0001-8804-4101
                Article
                24
                10.1038/s42003-018-0024-8
                6123706
                30271916
                beda5f8c-8423-4655-9b2d-99c57923cbd2
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 November 2017
                : 21 February 2018
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