A Point Of No Return Leading To Death During Heat-Shock In C. elegans

Longevity is a complex trait determined by genes, the environment, and their interactions. There is considerable insight into the genes associated with longevity and the interplay with environmental conditions. Most genes involved in the stress response play a major role in determining longevity. Yet, there is limited understanding of the mechanisms that determine how long stress can be tolerated before death becomes inevitable. Here, we leveraged the detection of an irreversible switch to death by studying global gene expression profiles in combination with survivorship following heat stress in the nematode C. elegans. By analysing the transcriptional response in a high-resolution time series of increasing stress exposures, we found a distinct shift in gene expression patterns between 3-4 hours into the stress response, separating an initially highly dynamic phase from a later mostly stagnant phase. Remarkably, this turning point in expression dynamics coincided with a phenotypic point of no return, as shown by a strong decrease in movement, survival and, progeny count in the days after; ultimately leading to death.