What is Xenohormesis?

Abstract

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.

Consumption of out-of-season orange modulates fat accumulation, morphology and gene expression in the adipose tissue of Fischer 344 rats

“…Afterwards, we converted this value to the average adipocyte weight using the adipocyte density (0.92 g/ml), and to obtain the total adipocyte number, and the weight of the IWAT deposit was divided by the average adipocyte weight, as proposed by Lemonnier [25]. Frequencies of adipocytes were obtained by distributing cells into two groups according to their area (< 5000 µm 2 or > 5000 µm 2 ) and calculating the percentage relative to the total number of counted cells.…”

“…The xenohormesis theory posits that plants synthesise small molecules or secondary metabolites when under a mild stress and that these molecules are detected by heterotrophs when ingested, activating a response that allows them to adapt to this new environment to survive [1,2]. For example, this can be activating energy accumulation when food is scarce or triggering reproductive changes during good weather [3,4].…”

Neurohormetic phytochemicals: An evolutionary–bioenergetic perspective

“…Data suggest that resveratrol can activate yeast Sir2/SIRT1, although whether this action of resveratrol results from a direct interaction with SIRT1 or is secondary to a less specific cellular stress response is unclear (Calabrese et al, 2010b; Kaeberlein et al, 2005a). Resveratrol was also reported to extend the lifespan of mice fed a high fat/calorie diet, which was associated with increased SIRT1 activity and mitochondrial biogenesis in muscle cells (Baur and Sinclair, 2008; Lagouge et al, 2006) Furthermore, resveratrol induces gene expression patterns in multiple tissues similar to those induced by intermittent fasting (Pearson et al, 2008). Growing evidence suggests that resveratrol can have beneficial effects on the health of aging animals including non-human primates and human (Dal-Pan et al, 2011a; Novelle et al, 2015).…”

GardeninA confers neuroprotection against environmental toxin in aDrosophilamodel of Parkinson’s disease

“…However, the antioxidant theory is very much alive in our society, a belief that fuels $3 billion global industry selling pills and drinks with "natural antioxidants" 14 . The emerging evidence suggests that phytochemicals may exert diseasepreventive and therapeutic actions by interacting with certain evolutionarily conserved cellular response pathways, as suggested by neurohormesis and xenohormesis hypotheses 13,15 .…”