| Increased transsulfuration mediates longevity and dietary restriction in Drosophila. | |
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MedLine Citation:
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PMID: 21930912 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mechanisms through which dietary restriction enhances health and longevity in diverse species are unclear. The transsulfuration pathway (TSP) is a highly conserved mechanism for metabolizing the sulfur-containing amino acids, methionine and cysteine. Here we show that Drosophila cystathionine β-synthase (dCBS), which catalyzes the rate-determining step in the TSP, is a positive regulator of lifespan in Drosophila and that the pathway is required for the effects of diet restriction on animal physiology and lifespan. dCBS activity was up-regulated in flies exposed to reduced nutrient conditions, and ubiquitous or neuron-specific transgenic overexpression of dCBS enhanced longevity in fully fed animals. Inhibition of the TSP abrogated the changes in lifespan, adiposity, and protein content that normally accompany diet restriction. RNAi-mediated knockdown of dCBS also limited lifespan extension by diet. Diet restriction reduced levels of protein translation in Drosophila, and we show that this is largely caused by increased metabolic commitment of methionine cycle intermediates to transsulfuration. However, dietary supplementation of methionine restored normal levels of protein synthesis to restricted animals without affecting lifespan, indicating that global reductions in translation alone are not required for diet-restriction longevity. Our results indicate a mechanism by which dietary restriction influences physiology and aging. |
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Authors:
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Hadise Kabil; Omer Kabil; Ruma Banerjee; Lawrence G Harshman; Scott D Pletcher |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-09-19 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 108 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-05 Completed Date: 2011-12-13 Revised Date: 2013-05-23 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 16831-6 Citation Subset: IM |
Affiliation:
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Department of Molecular and Integrative Physiology and Geriatrics Center, University of Michigan, Ann Arbor, MI 48109, USA. hadisekabil@gmail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animal Nutritional Physiological Phenomena
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physiology* Animals Blotting, Western Caloric Restriction Chromatography, High Pressure Liquid Cloning, Molecular Computational Biology Cystathionine beta-Synthase / genetics, metabolism* Cysteine / metabolism* DNA Primers / genetics Drosophila / physiology* Energy Intake / physiology* Gene Expression Regulation, Enzymologic / physiology Glutathione / metabolism Longevity / genetics, physiology* Methionine / metabolism* Polymerase Chain Reaction Protein Biosynthesis / physiology RNA Interference Triglycerides / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL58984/HL/NHLBI NIH HHS; P30-AG-013283/AG/NIA NIH HHS; R01AG023166/AG/NIA NIH HHS; R01AG030593/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/Triglycerides; 52-90-4/Cysteine; 63-68-3/Methionine; 70-18-8/Glutathione; EC 4.2.1.22/Cystathionine beta-Synthase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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