Hormesis, cell death and aging

Isabelle Martins,Guido Kroemer,Lorenzo Galluzzi

doi:10.18632/aging.100380

Abstract

Frequently, low doses of toxins and other stressors not only are harmless but also activate an adaptive stress response that raise the resistance of the organism against high doses of the same agent. This phenomenon, which is known as "hormesis", is best represented by ischemic preconditioning, the situation in which short ischemic episodes protect the brain and the heart against prolonged shortage of oxygen and nutrients. Many molecules that cause cell death also elicit autophagy, a cytoprotective mechanism relying on the digestion of potentially harmful intracellular structures, notably mitochondria. When high doses of these agents are employed, cells undergo mitochondrial outer membrane permeabilization and die. In contrast, low doses of such cytotoxic agents can activate hormesis in several paradigms, and this may explain the lifespan-prolonging potential of autophagy inducers including resveratrol and caloric restriction.

Highlights

Hormesis describes a favorable biological response to harmless doses of toxins and other stressors
Apoptosis is frequently viewed as a caspase-dependent cell death pathway in which a series of specific cysteine proteases are activated in a cascade of proteolytic maturation steps [9, 10]
Caspase inhibition rarely prevents cell death completely [10, 25,26,27], and multiple caspase-independent pathways may come into action [9, 28, 29]

Summary

Introduction

Hormesis (a neologism coined from the ancient Greek term hormáein, which literally means "to set in motion, impel, urge on") describes a favorable biological response to harmless doses of toxins and other stressors. Hormesis may constitute (one of) the mechanisms that allows stressed cells to avoid senescence and death, and might have some impact on the (patho)physiology of aging. Apoptosis is frequently viewed as a caspase-dependent cell death pathway in which a series of specific cysteine proteases are activated in a cascade of proteolytic maturation steps [9, 10].

Results

Conclusion