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

TY - JOUR

T1 - Loss of NDG-4 extends lifespan and stress resistance in Caenorhabditis elegans

AU - Brejning, Jeanette

AU - Nørgaard, Steffen

AU - Schøler, Lone

AU - Morthorst, Tine H.

AU - Jakobsen, Helle

AU - Lithgow, Gordon J.

AU - Jensen, Louise T.

AU - Olsen, Anders

PY - 2014/2/1

Y1 - 2014/2/1

N2 - 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.

AB - 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.

KW - Aging

KW - C. elegans

KW - Insulin signaling

KW - Lipid transport

KW - NDG-4

UR - http://www.scopus.com/inward/record.url?scp=84892540523&partnerID=8YFLogxK

U2 - 10.1111/acel.12165

DO - 10.1111/acel.12165

M3 - Journal article

C2 - 24286221

AN - SCOPUS:84892540523

SN - 1474-9718

VL - 13

SP - 156

EP - 164

JO - Aging Cell

JF - Aging Cell

IS - 1

ER -