Loss of NDG‐4 extends lifespan and stress resistance in Caenorhabditis elegans. Issue 1 (28th November 2013)

• Record Type: Journal Article
• Authors: Brejning, Jeanette; Nørgaard, Steffen; Schøler, Lone; Morthorst, Tine H.; Jakobsen, Helle; Lithgow, Gordon J.; Jensen, Louise T.; Olsen, Anders
• Is Part Of: Aging cell. Volume 13:Issue 1(2014:Feb.)
• Page Start: 156
• Page End: 164
• Publication Date: 2013-11-28
• Subjects: Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.12165
• Languages: English
• ISSNs: 1474-9718

Abstract

<abstract abstract-type="main" id="acel12165-abs-0001"> <title>Summary</title> <p>NDG‐4 is a predicted transmembrane acyltransferase protein that acts in the distribution of lipophilic factors. Consequently, <italic>ndg‐4</italic> 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 <italic>ndg‐4</italic> 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 <italic>ndg‐4</italic> mutants. Moreover, we find that <italic>nrf‐5</italic> and <italic>nrf‐6</italic> mutants also have extended lifespan and increased stress resistance, suggesting that altered lipid transport and metabolism play key roles in determining lifespan.</p> </abstract>