Loss of NDG-4 extends lifespan and stress resistance in Caenorhabditis elegans
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
Originalsprog | Engelsk |
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Tidsskrift | Aging Cell |
Vol/bind | 13 |
Udgave nummer | 1 |
Sider (fra-til) | 156-164 |
Antal sider | 9 |
ISSN | 1474-9718 |
DOI | |
Status | Udgivet - 1 feb. 2014 |
Eksternt udgivet | Ja |
ID: 204184110