An age-dependent reversal in the protective capacities of JNK signaling shortens Caenorhabditis elegans lifespan.

摘要: Stress-activated protein kinase (SAPK) pathways are evolutionarily conserved signaling modules that orchestrate protective responses to adverse environmental conditions. However, under certain conditions, their activation can be deleterious. Thus, of the c-Jun N-terminal (JNK) SAPK pathway exacerbates a diverse set pathologies, many which typical old age. The contexts determining whether outcome JNK is or detrimental not fully understood. Here, we show age an animal defines such context. Caenorhabditis elegans homolog, KGB-1, provides protection from heavy metals and folding stress in developing animals. found with onset adulthood, KGB-1 activity becomes detrimental, reducing resistance lifespan. Genetic analyses coupled fluorescent imaging linked this phenotypic switch age-dependent antagonistic modulation DAF-16/FOXO: enhanced DAF-16 nuclear localization transcriptional during development but decreased it adults. Epistasis showed was necessary sufficient explain some kgb-1-dependent phenotypes, all. identification early adulthood as point following contribution reverses beneficial sheds new light on involvement age-related pathologies. Furthermore, reversal has intriguing implications for our understanding aging.