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

Aging Cell

Jeanette Brejning²  Steffen Nørgaard²  Lone Schøler²  Tine H. Morthorst²  Helle Jakobsen²  Gordon J. Lithgow¹  Louise T. Jensen² 

[1] The Buck Institute for Research on Aging, Novato, CA, USA;Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark

关键词: aging;    C. elegans;    lipid transport;    NDG‐4;    insulin signaling;   

DOI  :  10.1111/acel.12165

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

CC BY   
© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.