What is Xenohormesis?

Polyphenols such as resveratrol and quercetin, which are produced by stressed plants, activate sirtuin enzymes and extend the lifespan of fungi and animals, ostensibly by mimicking the beneficial effects of caloric restriction. This observation raises an interesting question: Why should foreign molecules that are non-nutritive and seemingly unrelated to any endogenous molecule modulate the same biochemical pathways that mediate the response to an energy deficit? A possible explanation is that the sirtuin enzymes have evolved to respond to plant stress molecules as indicators of an impending deterioration of the environment. This idea has become known as the Xenohormesis Hypothesis, the name stemming from a combination of the prefix xeno-(for stranger) with hormesis (a protective response induced by mild stress). Here we review the evidence for xenohormesis in a broader context, taking into account the diverse spectrum of phytochemicals to which animals are exposed. We also consider alternative hypotheses that may explain some of the beneficial effects of plant-based foods. We suggest that xenohormesis, defined as an adaptive response in the physiology of an organism to molecular cues that are neither nutritive nor direct stressors, most likely occurs at some level. Whether this can fully or partially account for the beneficial effects of resveratrol and other phytochemicals remains to be seen. However, there is already sufficient cause to re-evaluate the relationship between complex organisms, including humans and their food.