Open AccessLifespan extension in hypomorphic daf‐2 mutants of Caenorhabditis elegans is partially mediated by glutathione transferase CeGSTP2‐2
Author(s) -
Ayyadevara Srinivas,
Dandapat Abhijit,
Singh Sharda P.,
Beneš Helen,
Zimniak Ludwika,
Reis Robert J. Shmookler,
Zimniak Piotr
Publication year - 2005
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2005.00172.x
Subject(s) - caenorhabditis elegans , biology , rna interference , mutant , 4 hydroxynonenal , glutathione s transferase , paraquat , glutathione , microbiology and biotechnology , biochemistry , gene , genetics , lipid peroxidation , oxidative stress , enzyme , rna
Summary Electrophilic stress caused by lipid peroxidation products such as 4‐hydroxynonenal (4‐HNE) and/or related compounds may contribute to aging. The major mode of 4‐HNE metabolism involves glutathione conjugation catalyzed by specialized glutathione transferases. We have previously shown that glutathione transferase CeGSTP2‐2, the product of the Caenorhabditis elegans gst‐10 gene, has the ability to conjugate 4‐HNE, and that its overexpression extends lifespan of C. elegans . We now demonstrate that the expression level of CeGSTP2‐2 correlates highly with lifespan in a series of hypomorphic daf‐2 mutants of C. elegans . The overexpression of CeGSTP2‐2 in daf‐2 is abrogated in daf‐16; daf‐2 mutants, indicating that expression of the gst‐10 gene is modulated by insulin‐like growth factor signaling. To determine whether the relationship between CeGSTP2‐2 and lifespan is causal, we used RNAi to knock down CeGSTP2‐2. Treatment with gst‐10 ‐specific dsRNA decreased CeGSTP2‐2 protein in wild‐type N2 and in daf‐2 strains to an approximately equal level. The ability to conjugate 4‐HNE was similarly decreased by RNAi, suggesting that the increment of that activity in daf‐2 over N2 is due largely to the overexpression of CeGSTP2‐2. RNAi‐mediated knock‐down of CeGSTP2‐2 led to an increased susceptibility to 4‐HNE, paraquat, and heat shock, and to a shortening of lifespan by 13% in both N2 and daf‐2 strains. These results indicate that CeGSTP2‐2 significantly contributes to the maintenance of the soma, and that this function is augmented in daf‐2 mutants concordantly with other longevity assurance genes, probably via insulin‐like growth factor signaling.