title: Loss of NDG-4 extends lifespan and stress resistance in Caenorhabditis elegans.
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.
authors.affiliation: Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 10C, Aarhus, 8000-DK, Denmark.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Brejning
authors.forename: Steffen
authors.initials: S
authors.lastname: Nørgaard
authors.forename: Lone
authors.initials: L
authors.lastname: Schøler
authors.forename: Tine H
authors.initials: TH
authors.lastname: Morthorst
authors.forename: Helle
authors.initials: H
authors.lastname: Jakobsen
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Lithgow
authors.forename: Louise T
authors.initials: LT
authors.lastname: Jensen
authors.forename: Anders
authors.initials: A
authors.lastname: Olsen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000382:microbiology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004032:Diet; D004789:Enzyme Activation; D005854:Germ Cells / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D008136:Longevity / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation; D015398:Signal Transduction; D013312:Stress, Physiological; D040521:Subcutaneous Tissue / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D007328:Insulin; D008565:Membrane Proteins; C499577:ndg-4 protein, C elegans
keywords: C. elegans; NDG-4; aging; insulin signaling; lipid transport