Lack of peroxisomal catalase causes a progeric phenotype in Caenorhabditis elegans.
Studies using the nematode Caenorhabditis elegans as a model system to investigate the aging process have implicated the insulin/insulin-like growth factor-I signaling pathway in the regulation of organismal longevity through its action on a subset of target genes. These targets can be classified into genes that shorten or extend life-span upon their induction. Genes that shorten life-span include a variety of stress response genes, among them genes encoding catalases; however, no evidence directly implicates catalases in the aging process of nematodes or other organisms. Using genetic mutants, we show that lack of peroxisomal catalase CTL-2 causes a progeric phenotype in C. elegans. Lack of peroxisomal catalase also affects the developmental program of C. elegans, since Deltactl-2 mutants exhibit decreased egg laying capacity. In contrast, lack of cytosolic catalase CTL-1 has no effect on either nematode aging or egg laying capacity. The Deltactl-2 mutation also shortens the maximum life-span of the long lived Deltaclk-1 mutant and accelerates the onset of its egg laying period. The more rapid aging of Deltactl-2 worms is apparently not due to increased carbonylation of the major C. elegans proteins, although altered peroxisome morphology in the Deltactl-2 mutant suggests that changes in peroxisomal function, including increased production of reactive oxygen species, underlie the progeric phenotype of the Deltactl-2 mutant. Our findings support an important role for peroxisomal catalase in both the development and aging of C. elegans and suggest the utility of the Deltactl-2 mutant as a convenient model for the study of aging and the human diseases acatalasemia and hypocatalasemia.
Department of Cell Biology, University of Alberta, Medical Sciences Building 5-14, Edmonton, Alberta T6G 2H7, Canada.
Oleh I
OI
Petriv
Richard A
RA
Rachubinski
D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics*; D002374:Catalase / Q000378:metabolism / Q000502:physiology*; D018076:DNA, Complementary / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D050356:Lipid Metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008957:Models, Genetic; D009154:Mutation; D016366:Open Reading Frames; D010455:Peptides / Q000737:chemistry; D020675:Peroxisomes / Q000201:enzymology* / Q000378:metabolism; D010641:Phenotype; D011371:Progeria / Q000235:genetics*; D013997:Time Factors
D018076:DNA, Complementary; D008164:Luminescent Proteins; D010455:Peptides; D049452:Green Fluorescent Proteins; D002374:Catalase