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DOI10.1073/pnas.2101977118
The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways
García-Flores L.A.; Green C.L.; Mitchell S.E.; Promislow D.E.L.; Lusseau D.; Douglas A.; Speakman J.R.
发表日期2021
ISSN0027-8424
卷号118期号:31
英文摘要The evolutionary context of why caloric restriction (CR) activates physiological mechanisms that slow the process of aging remains unclear. The main goal of this analysis was to identify, using metabolomics, the common pathways that are modulated across multiple tissues (brown adipose tissue, liver, plasma, and brain) to evaluate two alternative evolutionary models: the “disposable soma” and “clean cupboards” ideas. Across the four tissues, we identified more than 10,000 different metabolic features. CR altered the metabolome in a graded fashion. More restriction led to more changes. Most changes, however, were tissue specific, and in some cases, metabolites changed in opposite directions in different tissues. Only 38 common metabolic features responded to restriction in the same way across all four tissues. Fifty percent of the common altered metabolites were carboxylic acids and derivatives, as well as lipids and lipid-like molecules. The top five modulated canonical pathways were L-carnitine biosynthesis, NAD (nicotinamide adenine dinucleotide) biosynthesis from 2-amino-3-carboxymuconate semialdehyde, S-methyl-5′-thioadenosine degradation II, NAD biosynthesis II (from tryptophan), and transfer RNA (tRNA) charging. Although some pathways were modulated in common across tissues, none of these reflected somatic protection, and each tissue invoked its own idiosyncratic modulation of pathways to cope with the reduction in incoming energy. Consequently, this study provides greater support for the clean cupboards hypothesis than the disposable soma interpretation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Aging; Calorie restriction; Evolution; Life span; Metabolomics
语种英语
scopus关键词2 amino 3 carboxymuconate semialdehyde; adenosine; aldehyde; carboxylic acid derivative; carnitine; methyl 5' thioadenosine; nicotinamide adenine dinucleotide; transfer RNA; unclassified drug; amino acid synthesis; animal tissue; Article; biosynthesis; blood sampling; brain tissue; brown adipose tissue; caloric restriction; chromatography; controlled study; data processing; energy conservation; liver tissue; male; metabolome; metabolomics; mouse; nonhuman; prediction; signal transduction; spectrophotometry
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/238838
作者单位State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing, 100101, China; Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, AB39 2PN, United Kingdom; Department of Lab Medicine and Pathology, University of Washington, Seattle, WA 98195, United States; Department of Biology, University of Washington, Seattle, WA 98195, United States; Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Shenzhen, 518055, China; Center of Excellence for Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, 650223, China
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García-Flores L.A.,Green C.L.,Mitchell S.E.,et al. The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways[J],2021,118(31).
APA García-Flores L.A..,Green C.L..,Mitchell S.E..,Promislow D.E.L..,Lusseau D..,...&Speakman J.R..(2021).The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways.Proceedings of the National Academy of Sciences of the United States of America,118(31).
MLA García-Flores L.A.,et al."The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways".Proceedings of the National Academy of Sciences of the United States of America 118.31(2021).
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