Authors: Petriv OI; Rachubinski RA
Abstract: 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.
Keywords: Aging; Animals; Caenorhabditis elegans/*enzymology/*genetics; Catalase/metabolism/*physiology; DNA, Complementary/metabolism; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Lipid Metabolism; Luminescent Proteins/metabolism; Microscopy, Confocal; Microscopy, Electron; Models, Genetic; Mutation; Open Reading Frames; Peptides/chemistry; Peroxisomes/*enzymology/metabolism; Phenotype; Progeria/*genetics; Time Factors
Journal: The Journal of biological chemistry Volume: 279 Issue: 19 Pages: 19996-20001 Date: March 5, 2004 PMID: 14996832 |
Petriv OI, Rachubinski RA (2004) Lack of peroxisomal catalase causes a progeric phenotype in Caenorhabditis elegans. The Journal of biological chemistry 279: 19996-20001.
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