Abstract
Early exposure to some mild stresses can slow down the aging process and extend lifespan, raising the question of how early life stress might impact the somatic health of aged animals. Here, we reveal that early life heat experience triggers the establishment of epigenetic memory in soma, which promotes long-lasting stress responses and longevity in C. elegans. Unlike lethal heat shock, mild heat activates a unique transcriptional program mimicking pathogen defense responses, characterized by the enhanced expression of innate immune and detoxification genes.
Surprisingly, the expression of defense response genes persists long after heat exposure, conferring enhanced stress resistance even in aged animals. Further studies identify the histone acetyltransferase CBP-1 and the chromatin remodeling SWI/SNF complex as epigenetic modulators of the long-lasting defense responses. Histone acetylation is elevated by heat stress and maintained into agedness thereafter. Accordingly, histone acetylation levels were increased on the promoters of defense genes. Moreover, disruption of epigenetic memory abrogates the longevity response to early hormetic heat stress, indicating that long-lasting defense responses are crucial for the survival of aged animals. Together, our findings provide mechanistic insights into how temperature stress experienced in early life provides animals with lifetime health benefits.
Author Summary
Organism aging is a deleterious process characterized by the progressive decline of cellular and tissue functions in the late life stage. However, the rate of aging is often determined by an organism’s historic experiences that occur in early life. For example, some mild stresses experienced in early life can extend animal lifespan, implying that early stresses might impact the health of aged animals, the mechanisms of which remain largely unknown. Here, by using the model organism C.elegans, we reveal a mechanism of how early life heat stress impacts the health of aged animals and promotes longevity. We find that early exposure to mild heat activates basal innate immune and detoxification responses, which are surprisingly maintained long after temperature drop, even into aged-ness, and therefore contribute to lifespan extension. Remarkably, the long-lasting defense responses require epigenetic memory established by histone acetyltransferase CBP-1 and chromatin remodeling complex SWI/SNF. As a previous study has reported high temperature-induced transgenerational epigenetic effects in germline that involve histone methylation, our findings suggest that temperature may trigger distinct epigenetic changes in soma and germline, conferring adaptations in both the parental generation and their offspring.
