Exposing neurons of hermaphroditic C. elegans to high levels of either the Huntington’s disease–causing protein Q40 or the ligand Wnt triggers a stress pathway, the mitochondrial unfolded protein response (UPRmt), in many of their cells, including their oocytes. The UPRmt involves elevated copy numbers of the organelle’s genome and an accumulation of unfolded proteins (1). When researchers bred these animals with wild-type males that had not been stressed (2), they found that about 30 percent of the offspring continued to carry a “memory” of that stress, as evidenced by the UPRmt in their tissues (3). This transgenerational inheritance, the researchers found, was mediated by Wnt. Hermaphroditic offspring with the strongest stress responses were allowed to self-fertilize until up to 90 percent of offspring showed the UPRmt inherited from the experience of their ancestors—a “memory” passed down for as many as 50 generations (4). Worms with this stress-primed phenotype had increased resistance to other stressors such as heat and pathogens, and lived longer, but they grew more slowly and were less fertile than controls.
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