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Increased transsulfuration mediates longevity and dietary restriction in Drosophila

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-... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America Oct 4, 2011, Vol.108(40), p.16831
Main Author: Kabil, Hadise
Other Authors: Kabil, Omer , Banerjee, Ruma , Harshman, Lawrence , Pletcher, Scott
Format: Electronic Article Electronic Article
Language: English
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ID: ISSN: 00278424
Link: http://search.proquest.com/docview/896699872/?pq-origsite=primo
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title: Increased transsulfuration mediates longevity and dietary restriction in Drosophila
format: Article
creator:
  • Kabil, Hadise
  • Kabil, Omer
  • Banerjee, Ruma
  • Harshman, Lawrence
  • Pletcher, Scott
subjects:
  • Proteins
  • Insects
  • Signal Transduction
  • Diet
  • Physiology
ispartof: Proceedings of the National Academy of Sciences of the United States of America, Oct 4, 2011, Vol.108(40), p.16831
description: 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. [PUBLICATION ]
language: eng
source:
identifier: ISSN: 00278424
fulltext: fulltext
issn:
  • 00278424
  • 0027-8424
url: Link


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titleIncreased transsulfuration mediates longevity and dietary restriction in Drosophila
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subjectProteins ; Insects ; Signal Transduction ; Diet ; Physiology
descriptionThe 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. [PUBLICATION ]
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titleIncreased transsulfuration mediates longevity and dietary restriction in Drosophila
authorKabil, Hadise ; Kabil, Omer ; Banerjee, Ruma ; Harshman, Lawrence ; Pletcher, Scott
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abstractThe 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. [PUBLICATION ABSTRACT]
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urlhttp://search.proquest.com/docview/896699872/
pages16831-16836
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eissn10916490
date2011-10-04