Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans

Abstract

Summary Dietary restriction (DR) has the remarkable ability to extend lifespan and healthspan. A variety of DR regimens have been described in species ranging from yeast to mammals. However, whether different DR regimens extend lifespan via universal, distinct, or overlapping pathways is still an open question. Here we examine the genetic pathways that mediate longevity by different DR regimens in Caenorhabditis elegans . We have previously shown that the low‐energy sensing AMP‐activated protein kinase AMPK/ aak‐2 and the Forkhead transcription factor FoxO/ daf‐16 are necessary for longevity induced by a DR regimen that we developed (sDR). Here we find that AMPK and FoxO are necessary for longevity induced by another DR regimen, but are dispensable for the lifespan extension induced by two different DR methods. Intriguingly, AMPK is also necessary for the lifespan extension elicited by resveratrol, a natural polyphenol that mimics some aspects of DR. Conversely, we test if genes previously reported to mediate longevity by a variety of DR methods are necessary for sDR‐induced longevity. Although clk‐1 , a gene involved in ubiquinone biosynthesis, is also required for sDR‐induced lifespan extension, we find that four other genes ( sir‐2.1 , FoxA/ pha‐4 , skn‐1 , and hsf‐1 ) are all dispensable for longevity induced by sDR. Consistent with the observation that different DR methods extend lifespan by mostly independent genetic mechanisms, we find that the effects on lifespan of two different DR regimens are additive. Understanding the genetic network by which different DR regimens extend lifespan has important implications for harnessing the full benefits of DR on lifespan and healthspan.

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• Intestinal Autophagy Improves Healthspan and Longevity in C. elegans during Dietary Restriction · 2016
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• D-beta-hydroxybutyrate extends lifespan in C. elegans · 2014
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• Deletion of microRNA-80 activates dietary restriction to extend C. elegans healthspan and lifespan. · 2013
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• Malate and fumarate extend lifespan in Caenorhabditis elegans. · 2013
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• Worms need microbes too: microbiota, health and aging in Caenorhabditis elegans · 2013
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• Excessive folate synthesis limits lifespan in the <it>C. elegans</it>: <it>E. coli </it>aging model · 2012
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• The yeast forkhead transcription factors fkh1 and fkh2 regulate lifespan and stress response together with the anaphase-promoting complex. · 2012
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• Activation of AMPK by the Putative Dietary Restriction Mimetic Metformin Is Insufficient to Extend Lifespan in Drosophila · 2012
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• A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans · 2010
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• HIF-1 Modulates Dietary Restriction-Mediated Lifespan Extension via IRE-1 in Caenorhabditis elegans · 2009
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