Insulin and JNK: optimizing metabolic homeostasis and lifespan

Metabolic adaptation to environmental changes is crucial for the long-term survival of an organism. Signaling mechanisms that govern this adaptation thus influence lifespan. One such mechanism is the insulin/insulin-like growth factor signaling (IIS) pathway, a central regulator of metabolism in metazoans. Recent studies have identified the stress-responsive Jun-N-terminal kinase (JNK) pathway as a regulator of IIS signaling, providing a link between environmental challenges and metabolic regulation. JNK inhibits IIS activity and, thus, promotes lifespan extension and stress tolerance. Interestingly, this interaction is also at the center of age-related metabolic diseases. Here, we review recent advances illuminating the mechanisms of the JNK–IIS interaction and its implications for metabolic diseases and lifespan in metazoans.