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

Aging Cell

Kwame Twumasi-Boateng²  Tim W. Wang³  Linda Tsai³  Kuang-Hui Lee³  Ali Salehpour³  Sudarshan Bhat³  Man-Wah Tan¹ 

[1] Departments of Genetics and Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA;Graduate Group in Microbiology, University of California at Berkeley, CA 94720-3102, USA;Department of Integrative Biology, University of California at Berkeley, CA 94720-3102, USA

关键词: stress;    C. elegans;    JNK;    KGB‐1;    antagonistic pleiotropy;    lifespan;    stress;   

DOI  :  10.1111/j.1474-9726.2012.00829.x

来源: Wiley

【 摘 要 】

Summary

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

【 授权许可】

Unknown   
© 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland