A germline-to-soma signal triggers an age-related decline of mitochondrial stress response

Abstract The abilities of an organism to cope with extrinsic stresses and activate cellular stress responses decline during aging. The signals that modulate stress responses in aged animals remain to be elucidated. Here, we discover that feeding Caenorhabditis elegans ( C. elegans ) embryo lysates to adult worms enabled the animals to activate the mitochondrial unfolded protein response (UPR mt ) upon mitochondrial perturbations. This discovery led to subsequent investigations that unveil a hedgehog-like signal that is transmitted from the germline to the soma in adults to inhibit UPR mt in somatic tissues. Additionally, we find that the levels of germline-expressed piRNAs in adult animals markedly decreased. This reduction in piRNA levels coincides with the production and secretion of a hedgehog-like signal and suppression of the UPR mt in somatic cells. Building upon existing research, our study further elucidates the intricate mechanisms of germline-to-soma signaling and its role in modulating the trade-offs between reproduction and somatic maintenance within the context of organismal aging.