A cellular surveillance and defense system that delays aging phenotypes in <i>C. elegans</i>.

Physiological stresses, such as pathogen infection, are detected by &quot;cellular Surveillance Activated Detoxification and Defenses&quot; (cSADD) systems that trigger host defense responses. Aging is associated with physiological stress, including impaired mitochondrial function. Here, we investigated whether an endogenous cSADD pathway is activated during aging in <i>C. elegans</i>. We provide evidence that the transcription factor ZIP-2, a well-known immune response effector in <i>C. elegans</i>, is activated in response to age-associated mitochondrial dysfunction. ZIP-2 mitigates multiple aging phenotypes, including mitochondrial disintegration and reduced motility of the pharynx and intestine. Importantly, our data suggest that ZIP-2 is activated during aging independently of bacterial infection and of the transcription factors ATFS-1 and CEBP-2. Thus, ZIP-2 is a key component of an endogenous pathway that delays aging phenotypes in <i>C. elegans</i>. Our data suggest that aging coopted a compensatory strategy for regulation of aging process as a guarded process rather than a simple passive deterioration process.