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U-shaped dose-response relationships (hormesis) have been documented in numerous biological, toxicological, and pharmacological investigations. For example, in response to a mild 35 degrees C heat shock, the longevity of Caenorhabditis elegans exhibits an inverted U-shaped dose-response. By applying the demographic concept of heterogeneity, we find that this U-shaped curve for longevity response is driven by a U-shaped dose-response of initial mortality. When worms are subjected to mild heat shock, the initial mortality decreases compared to the control. This initial mortality benefit increases with moderate increases in the length of heat shock, peaking at a point that coincides with the induction of damage to the worms. The dose of heat shock that coincided with this benefit in initial mortality did not affect the rate of increase in mortality.

The U-Shaped Response of Initial Mortality in Caenorhabditis elegans to Mild Heat Shock: Does It Explain Recent Trends in Human Mortality?