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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Cited by papers we hold 21

• Dietary regulation in health and disease · 2022
  No notice
• Polyunsaturated fatty acids and p38-MAPK link metabolic reprogramming to cytoprotective gene expression during dietary restriction · 2020
  Not checked
• Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms · 2020
  No notice
• Dietary sulfur amino acid restriction upregulates DICER to confer beneficial effects · 2019
  Not checked
• Neuronal TORC1 modulates longevity via AMPK and cell nonautonomous regulation of mitochondrial dynamics in C. elegans · 2019
  No notice
• AMPK and vacuole-associated Atg14p orchestrate μ-lipophagy for energy production and long-term survival under glucose starvation · 2017
  No notice
• Longitudinal imaging of Caenorhabditis elegans in a microfabricated device reveals variation in behavioral decline during aging · 2017
  No notice
• Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects · 2017
  No notice
• Intestinal Autophagy Improves Healthspan and Longevity in C. elegans during Dietary Restriction · 2016
  Corrected
• Lifespan-regulating genes in C. elegans · 2016
  No notice
• D-beta-hydroxybutyrate extends lifespan in C. elegans · 2014
  No notice
• AMPK: Regulating Energy Balance at the Cellular and Whole Body Levels · 2014
  No notice
• Deletion of microRNA-80 activates dietary restriction to extend C. elegans healthspan and lifespan. · 2013
  Not checked
• Malate and fumarate extend lifespan in Caenorhabditis elegans. · 2013
  Not checked
• Worms need microbes too: microbiota, health and aging in Caenorhabditis elegans · 2013
  No notice
• Excessive folate synthesis limits lifespan in the <it>C. elegans</it>: <it>E. coli </it>aging model · 2012
  Not checked
• The yeast forkhead transcription factors fkh1 and fkh2 regulate lifespan and stress response together with the anaphase-promoting complex. · 2012
  Not checked
• Activation of AMPK by the Putative Dietary Restriction Mimetic Metformin Is Insufficient to Extend Lifespan in Drosophila · 2012
  No notice
• A Mitochondrial Superoxide Signal Triggers Increased Longevity in Caenorhabditis elegans · 2010
  No notice
• HIF-1 Modulates Dietary Restriction-Mediated Lifespan Extension via IRE-1 in Caenorhabditis elegans · 2009
  No notice

and 1 more

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