I have couple posts (1,2,3) in this blog on the topic of "eat less live longer". All of them were using worm as the model system. The following paper using fruit fly and convincingly suggested a causal mechanism among dietary restriction, enhanced mitochondrial function and extension of lifespan.
Cell. 2009 Oct 2;139(1):149-60.
4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila.
Zid BM, Rogers AN, Katewa SD, Vargas MA, Kolipinski MC, Lu TA, Benzer S, Kapahi P.
California Institute of Technology, Pasadena, CA 91125, USA.
Dietary restriction (DR) extends lifespan in multiple species. To examine the mechanisms of lifespan extension upon DR, we assayed genome-wide translational changes in Drosophila. A number of nuclear encoded mitochondrial genes, including those in Complex I and IV of the electron transport chain, showed increased ribosomal loading and enhanced overall activity upon DR. We found that various mitochondrial genes possessed shorter and less structured 5'UTRs, which were important for their enhanced mRNA translation. The translational repressor 4E-BP, the eukaryotic translation initiation factor 4E binding protein, was upregulated upon DR and mediated DR dependent changes in mitochondrial activity and lifespan extension. Inhibition of individual mitochondrial subunits from Complex I and IV diminished the lifespan extension obtained upon DR, reflecting the importance of enhanced mitochondrial function during DR. Our results imply that translational regulation of nuclear-encoded mitochondrial gene expression by 4E-BP plays an important role in lifespan extension upon DR. For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.
John Abrams
University of Texas Southwestern Medical Center at Dallas, United States of America
Cell BiologyIt has long been known that dietary restriction is a universal treatment that extends lifespan. However, gratifying explanations for this cause-effect relationship are lacking. This illuminating work presents several provocative scenarios that could fundamentally shift conventional wisdom on possible mechanisms. In particular, an observed increased expression of nuclear encoded mitochondrial genes suggests there is an increase in mitochondrial activity during dietary restriction.
The authors conduct genome-wide analyses on dietary restriction. They find that the translation initiation factor 4E binding protein coordinately up-regulates translation of nuclear encoded mitochondrial genes. The work establishes causal links between enhanced mitochondrial respiration/biogenesis and enhanced lifespan caused by dietary restriction.
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