Transcriptomic analysis of mitohormesis associated with lifespan extension in Caenorhabditis elegans

Non-lethal exposure to mitochondrial stress has been shown to have beneficial effects due to activation of signalling pathways, including the mitochondrial unfolded protein response (UPR ^mt ). Activation of UPR ^mt restores function of the mitochondria and improves general health and longevity in multiple model systems, termed mitohormesis. In C. elegans , mitohormesis can be accomplished by electron transport chain inhibition, decline in mitochondrial translation, decreased mitochondrial import, and numerous other methods that activate UPR ^mt . However, not all methods that activate UPR ^mt can promote longevity. These and other studies have started to question whether UPR ^MT is directly correlated with longevity. Here, we attempt to address this controversy by unravelling the complex molecular regulation of longevity of the nematode under different mitochondrial stressors that induce UPR ^mt by performing RNA-sequencing to profile transcriptome changes. Using this comprehensive and unbiased approach, we aim to determine whether specific transcriptomic changes can reveal a correlation between UPR ^mt and longevity. Altogether this study will provide mechanistic insights on mitohormesis and how it correlates with lifespan of C. elegans .