In this elegant study, Li and colleagues show how the mitochondrial unfolded protein response (UPRmt) can promote longevity in Caenorhabditis elegans. Using a focused RNAi screen, the authors discover that CREB-binding protein 1 (CBP-1) is a crucial mediator of the UPRmt, and that it is also involved in mitochondrial-stress induced immune activation, as well as in the reduction of amyloid-β aggregation. In mammalian cells, CBP/p300 is the homologue of CBP-1, with transcripts of this protein in human and mouse populations correlating with increased longevity. Mechanistically, CBP-1 works upstream of JMJD-1.2 and JMJD-3.1 (histone demethylases) and downstream of ATFS-1 to bring about its beneficial effects.
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