Hormesis is a biological phenomenon, whereby exposure to low levels of toxic agents or conditions increases organismal viability. It thus represents a beneficial aspect of adaptive responses to harmful environmental stimuli. Here we show that hormesis effects induced in the parental generation can be passed on to the descendants in Caenorhabditis elegans. Animals subjected to various stressors during developmental stages exhibit increased resistance to oxidative stress and proteotoxicity. The increased resistance is transmitted to the subsequent generations grown under unstressed conditions through epigenetic alterations. Our analysis reveal that the insulin/insulin-like growth factor (IGF) signalling effector DAF-16/FOXO and the heat-shock factor HSF-1 in the parental somatic cells mediate the formation of epigenetic memory, which is maintained through the histone H3 lysine 4 trimethylase complex in the germline across generations. The elicitation of memory requires the transcription factor SKN-1/Nrf in somatic tissues. We propose that germ-to-soma communication across generations is an essential framework for the transgenerational inheritance of acquired traits, which provides the offspring with survival advantages to deal with environmental perturbation.

Summary Previous studies have revealed the importance of inter-tissue communications for lifespan regulation. However, the inter-tissue network responsible for lifespan regulation is not well understood, even in a simple organism Caenorhabditis elegans . To understand the mechanisms underlying systemic lifespan regulation, we focused on lifespan regulation by the insulin/insulin-like growth factor-1 signaling (IIS) pathway; IIS reduction activates the DAF-16/FOXO transcription factor, which results in lifespan extension. Our tissue-specific knockdown and knockout analyses demonstrated that IIS reduction in neurons and the intestine markedly extended lifespan. DAF-16 activation in neurons resulted in DAF-16 activation in the intestine and vice versa. Our dual gene manipulation method revealed that intestinal and neuronal DAF-16 mediate longevity induced by daf-2 knockout in neurons and the intestine, respectively. In addition, the systemic regulation of intestinal DAF-16 required the IIS pathway in intestinal and neurons. Collectively, these results highlight the importance of the neuronal DAF-16-to-intestinal DAF-16 communication for organismal lifespan regulation.

Highlights d Intestine ash-2 KO increases stress resistance in a germline RBR-2-dependent manner d Intestine ash-2 deficiency reduces H3K4me3 levels in the germline d Intestine-to-germline communication intergenerationally regulates stress resistance d F08F1.3 partly mediates the intertissue communication