Research Article: Hormesis, cell death and aging

Date Published: September 8, 2011

Publisher: Impact Journals LLC

Author(s): Isabelle Martins, Lorenzo Galluzzi, Guido Kroemer.



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.

Partial Text

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-stimulating compounds initiate an adaptive stress response that renders cells/organisms resistant against high (and normally harmful) doses of the same agent. On the theoretical level, hormesis may constitute (one of) the mechanisms that allows stressed cells to avoid senescence and death, and hence might have some impact on the (patho)physiology of aging. Thus, measures that reportedly prolong the healthy lifespan of multiple species, such as caloric restriction and the administration of resveratrol [1-6], may do so by inducing a hormetic response [7,8]. In this article, we will examine the molecular circuitries that link cellular stress and death, and how these pathways can get uncoupled during hormetic responses.





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