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      The dietary proportion of essential amino acids and Sir2 influence lifespan in the honeybee

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          Abstract

          Dietary essential amino acids have an important influence on the lifespan and fitness of animals. The expression of the NAD +-dependent histone deacetylase, Sir2, can be influenced by diet, but its role in the extension of lifespan has recently been challenged. Here, we used the honeybee to test how the dietary balance of carbohydrates and essential amino acids and/or Sir2 affected lifespan. Using liquid diets varying in their ratio of essential amino acids to carbohydrate (EAA:C), we found that adult worker bees fed diets high in essential amino acids (≥1:10) had shorter lifespans than bees fed diets containing low levels of dietary amino acids. Bees fed a 1:500 EAA:C diet lived longer and, in contrast to bees fed any of the other diets, expressed Sir2 at levels tenfold higher or more than bees fed a 1:5 EAA:C diet. When bees were fed the 1:500 diet, small interfering RNA (siRNA)-mediated knock-down of Sir2 expression shortened lifespan but did not reduce survival to the same extent as the 1:5 diet, indicating that Sir2 contributes to mechanisms that determine lifespan in response to differences in macronutrient intake but is not the sole determinant. These data show that the ratio of dietary amino acids to carbohydrate influences Sir2 expression and clearly demonstrate that Sir2 is one of the factors that can determine honeybee lifespan. We propose that effects of dietary amino acids and Sir2 on lifespan may depend on the simultaneous activation of multiple nutrient sensors that respond to relative levels of essential amino acids and carbohydrates.

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          The online version of this article (doi:10.1007/s11357-014-9649-9) contains supplementary material, which is available to authorized users.

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          Most cited references41

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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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            Sir2 mediates longevity in the fly through a pathway related to calorie restriction.

            Calorie restriction can extend life span in a variety of species including mammals, flies, nematodes, and yeast. Despite the importance of this nearly universal effect, little is understood about the molecular mechanisms that mediate the life-span-extending effect of calorie restriction in metazoans. Sir2 is known to be involved in life span determination and calorie restriction in yeast mother cells. In nematodes increased Sir2 can extend life span, but a direct link to calorie restriction has not been demonstrated. We now report that Sir2 is directly involved in the calorie-restriction life-span-extending pathway in Drosophila. We demonstrate that an increase in Drosophila Sir2 (dSir2) extends life span, whereas a decrease in dSir2 blocks the life-span-extending effect of calorie reduction or rpd3 mutations. These data lead us to propose a genetic pathway by which calorie restriction extends life span and provides a framework for genetic and pharmacological studies of life span extension in metazoans.
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              RNA interference in Lepidoptera: an overview of successful and unsuccessful studies and implications for experimental design.

              Gene silencing through RNA interference (RNAi) has revolutionized the study of gene function, particularly in non-model insects. However, in Lepidoptera (moths and butterflies) RNAi has many times proven to be difficult to achieve. Most of the negative results have been anecdotal and the positive experiments have not been collected in such a way that they are possible to analyze. In this review, we have collected detailed data from more than 150 experiments including all to date published and many unpublished experiments. Despite a large variation in the data, trends that are found are that RNAi is particularly successful in the family Saturniidae and in genes involved in immunity. On the contrary, gene expression in epidermal tissues seems to be most difficult to silence. In addition, gene silencing by feeding dsRNA requires high concentrations for success. Possible causes for the variability of success in RNAi experiments in Lepidoptera are discussed. The review also points to a need to further investigate the mechanism of RNAi in lepidopteran insects and its possible connection to the innate immune response. Our general understanding of RNAi in Lepidoptera will be further aided in the future as our public database at http://insectacentral.org/RNAi will continue to gather information on RNAi experiments. Copyright © 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                +44-191-2225986 , +44-191-2227424 , dianne.ford@ncl.ac.uk
                Journal
                Age (Dordr)
                Age
                Springer Netherlands (Dordrecht )
                0161-9152
                1574-4647
                10 April 2014
                10 April 2014
                June 2014
                : 36
                : 3
                : 9649
                Affiliations
                [ ]Institute of Neuroscience, Newcastle University, Medical School, Newcastle upon Tyne, NE2 4HH UK
                [ ]Institute for Cell and Molecular Biosciences and Institute for Ageing and Health, Newcastle University, Medical School, Newcastle upon Tyne, NE2 4HH UK
                Article
                9649
                10.1007/s11357-014-9649-9
                4082578
                24715247
                adbdd9d2-8905-4a63-985f-1af04be13309
                © The Author(s) 2014

                Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

                History
                : 25 September 2013
                : 24 March 2014
                Categories
                Article
                Custom metadata
                © American Aging Association 2014

                Geriatric medicine
                honeybees,sir2,diet,protein,essential amino acids,lifespan
                Geriatric medicine
                honeybees, sir2, diet, protein, essential amino acids, lifespan

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