Loss of NDG-4 extends lifespan and stress resistance in Caenorhabditis elegans

Jeanette Brejning, Steffen Nørgaard, Lone Schøler, Tine H Morthorst, Helle Jakobsen, Gordon J Lithgow, Anders Olsen

Research output: Contribution to journalJournal articleResearchpeer-review

12 Citations (Scopus)

Abstract

NDG-4 is a predicted transmembrane acyltransferase protein that acts in the distribution of lipophilic factors. Consequently, ndg-4 mutants lay eggs with a pale appearance due to lack of yolk, and they are resistant to sterility caused by dietary supplementation with the long-chain omega-6 polyunsaturated fatty acid dihommogamma-linolenic acid (DGLA). Two other proteins, NRF-5 and NRF-6, a homolog of a mammalian secreted lipid binding protein and a NDG-4 homolog, respectively, have previously been shown to function in the same lipid transport pathway. Here, we report that mutation of the NDG-4 protein results in increased organismal stress resistance and lifespan. When NDG-4 function and insulin/IGF-1 signaling are reduced simultaneously, maximum lifespan is increased almost fivefold. Thus, longevity conferred by mutation of ndg-4 is partially overlapping with insulin signaling. The nuclear hormone receptor NHR-80 (HNF4 homolog) is required for longevity in germline less animals. We find that NHR-80 is also required for longevity of ndg-4 mutants. Moreover, we find that nrf-5 and nrf-6 mutants also have extended lifespan and increased stress resistance, suggesting that altered lipid transport and metabolism play key roles in determining lifespan.

Original languageEnglish
JournalAging Cell
Volume13
Issue number1
Pages (from-to)156-64
Number of pages9
ISSN1474-9718
DOIs
Publication statusPublished - Feb 2014
Externally publishedYes

Keywords

  • Animals
  • Caenorhabditis elegans/enzymology
  • Caenorhabditis elegans Proteins/metabolism
  • Diet
  • Enzyme Activation
  • Germ Cells/metabolism
  • Insulin/metabolism
  • Intestines/cytology
  • Longevity/physiology
  • Membrane Proteins/metabolism
  • Mutation
  • Signal Transduction
  • Stress, Physiological
  • Subcutaneous Tissue/metabolism

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