Regulation of Drosophila lifespan by JNK signaling

Cellular responses to extrinsic and intrinsic insults have to be carefully regulated to properly coordinate cytoprotection, repair processes, cell proliferation and apoptosis. Stress signaling pathways, most prominently the Jun-N-terminal Kinase (JNK) pathway, are critical regulators of such cellular responses and have accordingly been implicated in the regulation of lifespan in various organisms. JNK signaling promotes cytoprotective gene expression, but also interacts with the insulin signaling pathway to influence growth, metabolism, stress tolerance and regeneration. Here, we review recent studies in Drosophila that elucidate the tissue-specific and systemic consequences of JNK activation that ultimately impact lifespan of the organism. ► JNK signaling is a conserved regulator of lifespan. ► Multiple physiological processes are controlled by JNK to influence lifespan. ► JNK promotes oxidative stress tolerance and regulates apoptosis. ► Antagonism between JNK and insulin signaling influences metabolic homeostasis and lifespan. ► Excessive JNK activity negatively influences lifespan by disrupting intestinal regeneration.