Mitochondrial dysfunction is a hallmark of aging, and plays a pivotal role in all neurodegenerative diseases of aging. Recently we have found that the activation of the innate immune response in C. elegans peripheral tissue, in particular intestinal cells, can protect its neurons from degeneration induced by mitochondrial dysfunction. Specifically, we found that the p38 mitogen-activated protein kinase (MAPK; the mammalian p38α ortholog) and the CREB like transcription factor ATF-7-mediated innate immune pathway activated in C. elegans intestinal cells prevented rotenone induced-neurodegeneration. The neuroprotective effects of p38MAPK/ATF-7 immunity activated in the gut was through the enhancement of mitophagy. Given the bacterial origins of mitochondria this suggests the intruging possibility that similarities between mitophagy and xenophagy-the immune response activated by pathogen associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs), may play protective roles in degenrative diseases. We are currently investigating the molecular mechanisms by which mitophagy is activated by the innate immune response.