Increased transsulfuration mediates longevity and dietary restriction in Drosophila

Hadise Kabil, Omer Kabil, Ruma Banerjee, Lawrence G. Harshman, Scott D. Pletcher

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)16831-16836
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number40
DOIs
Publication statusPublished - Oct 4 2011

    Fingerprint

Keywords

  • Essential amino acids
  • Healthspan
  • Hydrogen sulfide
  • Metabolism

ASJC Scopus subject areas

  • General

Cite this