New considerations on hormetic response against oxidative stress

Abstract

In order to survive living organisms have developed multiple mechanisms to deal with tough environmental conditions. Hormesis is defined as a process in which exposure to a low dose of a chemical agent or environmental factor that is damaging at higher doses induces an adaptive beneficial effect on the cell or organism. In this paper, we examine several ideas that might be taken into consideration before using hormesis as a therapeutic tool to improve health and life span, and hopefully will open the discussion for new and interesting debates regard hormesis. The first one is to understand that the same stressor or inductor can activate different pathways in a parallel or dual response, which might lead to diverse outcomes. Another idea is related to the mechanisms involved in activating Nrf2, which might be different and have diverse hormetic effects.Last, we discuss mild oxidative stress in association to low-grade chronic inflammation as a stimulating avenue to be explored and the unexpected effects proposed by the obesity paradox theory. All the previous might help to clarify the reasons why centenarians are able to reach the extreme limits of human life span, which could probably be related to the way they deal with homeostasis maintenance, providing an opportunity for hormesis to intervene significantly.

Fig. 1

Hormetic mechanism during the “obesity paradox”. All the organisms are exposed to a great collection of stressors during their lifespan, which might promote oxidative stress, cellular damage and inflammation. However, young organisms use inflammation as a beneficial signal to deal against different kind of stressors and stimulate tissue repair (turquoise). During the adulthood of an obese individual (green), inflammation signals produced by enlarged adipocytes might not only impair normal tissue repair, but might broaden oxidative stresses and cellular injury, leading to metabolic disorders and disease. The obesity paradox theory proposes that life time exposure to low-grade inflammation produced by adipocytes might induce an hormetic mechanism which could be able to have a better glucose metabolism, damage responses etc., which would protect the organism against chronic diseases during old age (lilac)