Review Volume 3, Issue 9 pp 821—828

Hormesis, cell death and aging

Isabelle Martins1,2,3, *,, Lorenzo Galluzzi1,2,3, *,, Guido Kroemer1,4,5,6,7, ,

  • 1 INSERM, U848, 94805 Villejuif, France
  • 2 Institut Gustave Roussy, 94805 Villejuif, France
  • 3 Université Paris Sud XI, 94270 Le Kremlin-Bicêtre, France
  • 4 Metabolomics Platform, Institut Gustave Roussy, 94805 Villejuif, France
  • 5 Centre de Recherche des Cordeliers, 75006 Paris, France
  • 6 Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France
  • 7 Université Paris Descartes, Faculté de Médecine, 75006 Paris, France
* Equal contribution

Received: September 6, 2011       Accepted: September 8, 2011       Published: September 8, 2011
How to Cite


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.


AIF: apoptosis-inducing factor; DISC: death-inducing signaling complex; IPC: ischemic preconditioning; MOMP: mitochondrial outer membrane permeabilization; UCP2: uncoupling protein 2; XIAP: X-linked inhibitor of apoptosis protein.

View Full Text Download PDF