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 Δctl-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 Δctl-2 mutation also shortens the maximum life-span of the long lived Δclk-1 mutant and accelerates the onset of its egg laying period. The more rapid aging of Δctl-2 worms is apparently not due to increased carbonylation of the major C. elegans proteins, although altered peroxisome morphology in the Δctl-2 mutant suggests that changes in peroxisomal function, including increased production of reactive oxygen species, underlie the progeric phenotype of the Δctl-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 Δctl-2 mutant as a convenient model for the study of aging and the human diseases acatalasemia and hypocatalasemia. 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 Δctl-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 Δctl-2 mutation also shortens the maximum life-span of the long lived Δclk-1 mutant and accelerates the onset of its egg laying period. The more rapid aging of Δctl-2 worms is apparently not due to increased carbonylation of the major C. elegans proteins, although altered peroxisome morphology in the Δctl-2 mutant suggests that changes in peroxisomal function, including increased production of reactive oxygen species, underlie the progeric phenotype of the Δctl-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 Δctl-2 mutant as a convenient model for the study of aging and the human diseases acatalasemia and hypocatalasemia. A subset of genes of the nematode Caenorhabditis elegans are direct targets (1McElwee J. Bubb K. Thomas J.H. Aging Cell. 2003; 2: 111-121Crossref PubMed Scopus (334) Google 2003; PubMed Scopus Google of the PubMed Scopus Google a of the insulin/insulin-like growth signaling pathway implicated in the aging process (1McElwee J. Bubb K. Thomas J.H. Aging Cell. 2003; 2: 111-121Crossref PubMed Scopus (334) Google C. 2003; PubMed Scopus Google These target genes in their of and can be directly or upon of J. C. 2003; PubMed Scopus Google regulation of target genes is to to an or life-span for the the target genes are encoding and in the stress response and genes encoding for as the the and the catalases CTL-1 and CTL-2 J. C. 2003; PubMed Scopus Google reactive oxygen reactive oxygen and catalases are of reactive oxygen and and have to important in the aging process in C. elegans J. PubMed Scopus Google are increased in the C. elegans mutants J. PubMed Scopus Google K. PubMed Scopus Google PubMed Scopus Google K. K. and K. 2003; PubMed Scopus Google J. C. PubMed Scopus Google catalase is decreased in a lived for PubMed Scopus Google The mutation also the in catalase in mutants K. 2003; PubMed Scopus Google to the insulin/insulin-like growth factor-I signaling and stress are also to be major of the aging process in C. elegans and other model K. 2003; PubMed Scopus Google PubMed Scopus Google of that extend and catalase and have to be increased in a K. 2003; PubMed Scopus Google A in and catalase and to stress has also in long lived mutants PubMed Scopus Google the the nematode is and to the catalase are PubMed Scopus Google K. K. PubMed Scopus Google of worms their 2003; PubMed Scopus Google J. PubMed Scopus Google These and other findings model PubMed Scopus Google PubMed Scopus Google J. PubMed Scopus Google PubMed Scopus Google PubMed Google suggest that catalases an important role in the aging however, a on the role of catalases in the aging process in C. elegans of process in mutant for the catalase of the cytosolic CTL-1 and the peroxisomal have for C. elegans J. C. J.H. J. PubMed Scopus Google J. PubMed Scopus Google A to CTL-1 directly in the of aging in C. elegans J. C. J.H. J. PubMed Scopus Google of the catalase in C. elegans, the of catalase genes a of not to the of as C. 2003; PubMed Scopus Google J. 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