RESUMO
The two parts of the Caenorhabditis elegans reproductive system, the germ cells and the somatic reproductive tissues, each influence the life span of the animal. Removing the germ cells increases longevity, and this life span extension requires the somatic gonad. Here we show that the somatic gonad and the germ cells make distinct contributions to life span determination. The life span increase produced by loss of the germ cells requires the DAF-16/FOXO transcription factor. In response to germ-cell removal, DAF-16 accumulates in nuclei. We find that the somatic gonad is not required for DAF-16 nuclear accumulation or for the increased stress resistance that is produced by germ-cell removal. The somatic gonad is required, however, for expression of specific DAF-16 target genes. DAF-16 is known to be activated by reduced insulin/IGF-1 signaling in C. elegans. In certain insulin/IGF-1-pathway mutants, the somatic gonad is not required for germ-cell removal to extend life span. Our genetic experiments suggest that these mutations reduce insulin/IGF-1 signaling below a critical threshold level. At these low levels of insulin/IGF-1 signaling, factors normally provided by the somatic gonad are no longer needed for germ-cell removal to increase the expression of DAF-16 target genes.
Assuntos
Caenorhabditis elegans/fisiologia , Células Germinativas/metabolismo , Longevidade/fisiologia , Animais , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Núcleo Celular/metabolismo , Fatores de Transcrição Forkhead , Regulação da Expressão Gênica no Desenvolvimento , Gônadas/citologia , Gônadas/metabolismo , Insulina/metabolismo , Modelos Biológicos , Mutação/genética , Estresse Oxidativo , Transporte Proteico , Receptor de Insulina/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Reprodução , Transdução de Sinais , Superóxido Dismutase/metabolismo , Fatores de Transcrição/metabolismoAssuntos
Caenorhabditis elegans/fisiologia , Longevidade , Receptor de Insulina/fisiologia , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/fisiologia , Genes de Helmintos , Gônadas/fisiologia , Movimento , Mutação , Interferência de RNA , Receptor de Insulina/genéticaRESUMO
To explore the role of mitochondrial activity in the aging process, we have lowered the activity of the electron transport chain and adenosine 5'-triphosphate (ATP) synthase with RNA interference (RNAi) in Caenorhabditis elegans. These perturbations reduced body size and behavioral rates and extended adult life-span. Restoring messenger RNA to near-normal levels during adulthood did not elevate ATP levels and did not correct any of these phenotypes. Conversely, inhibiting respiratory-chain components during adulthood only did not reset behavioral rates and did not affect life-span. Thus, the developing animal appears to contain a regulatory system that monitors mitochondrial activity early in life and, in response, establishes rates of respiration, behavior, and aging that persist during adulthood.
Assuntos
Envelhecimento , Caenorhabditis elegans/fisiologia , Transporte de Elétrons , Mitocôndrias/metabolismo , Consumo de Oxigênio , Animais , Comportamento Animal , Caenorhabditis elegans/citologia , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Tamanho Celular , Complexo I de Transporte de Elétrons , Complexo III da Cadeia de Transporte de Elétrons/genética , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Endorribonucleases/genética , Endorribonucleases/metabolismo , Comportamento Alimentar , Fatores de Transcrição Forkhead , Proteínas Ferro-Enxofre/genética , Proteínas Ferro-Enxofre/metabolismo , Longevidade , ATPases Mitocondriais Próton-Translocadoras/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Movimento , NADH Desidrogenase/genética , NADH Desidrogenase/metabolismo , NADH NADPH Oxirredutases/genética , NADH NADPH Oxirredutases/metabolismo , Fenótipo , Interferência de RNA , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Ribonuclease III , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The germ line of the nematode Caenorhabditis elegans influences life-span; when the germ-line precursor cells are removed, life-span is increased dramatically. We find that neither sperm, nor oocytes, nor meiotic precursor cells are responsible for this effect. Rather life-span is influenced by the proliferating germ-line stem cells. These cells, as well as a downstream transcriptional regulator, act in the adult to influence aging, indicating that the aging process remains plastic during adulthood. We propose that the germ-line stem cells affect life-span by influencing the production of, or the response to, a steroid hormone that promotes longevity.