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

¹ Institute for Behavioral Genetics, University of Colorado at Boulder.
² Center for Population Health and Aging, Duke University, Durham, North Carolina.

Address correspondence to Deqing Wu, Institute for Behavioral Genetics, University of Colorado at Boulder, UCB 447, Boulder, CO 80309. E-mail: deqing.wu{at}gmail.com

U-shaped dose-response relationships (hormesis) have been documented in numerous biological, toxicological, and pharmacological investigations. For example, in response to a mild 35°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.

Key Words: Hidden heterogeneity • Initial mortality • U-shaped response • Heat shock • Caenorhabditis elegans