La réponse des cellules aux stress : relation avec le processus de vieillissement et la pathologie.

Abstract

La senescence replicative in vitro est caracterisee par un ralentissement puis un arret irreversible de la multiplication des types cellulaires proliferatifs. Des stress subletaux peuvent accelerer le processus de vieillissement cellulaire et entrainer l' apparition de ses principaux marqueurs que sont l' alteration morphologique, le raccourcissement des telomeres, la perte du processus proliferatif. L' etude fondamentale des processus cellulaires et moleculaires lies, en particulier, aux modifications irreversibles dues a l' effet de stress non letaux peut etre replacee dans le contexte des affections liees au vieillissement. Une interpretation globale fondee sur la theorie de la thermodynamique des systemes ouverts loin de l' equilibre permet d' expliquer comment des stress de diverses natures physico-chimiques peuvent entrainer un vieillissement accelere des cellules.

In vitro replicative senescence is characterized by an irreversible growth arrest of proliferative cells. Different regulatory processes briefly described herein have been discovered which can at least in part explain the occurrence of replicative senescence. The question is to know how stress and stimulations can influence these regulatory processes. Different groups have proposed that sublethal stress can accelerate the process of cellular ageing since the main biomarkers of cellular ageing appear irreversibly after sublethal stress such as a morphology typical of old cells, an irreversible loss of the proliferative capacity, the appearance of senescence-associated beta-galactosidase activity, the shortening of telomeres, the accumulation of the senescence specific lipofuscin pigment, or the continuous expression of growth inhibitors. A global interpretation based on the theory of far from equilibrium thermodynamical systems can explain how different kinds of physico-chemical stress lead to the process of accelerated ageing. This theory can also explain why the presence of substrates of the energy metabolism or pharmacological molecules enhancing the energy metabolism protect cells against accelerated ageing and cell death. Stress induces cellular responses which can generate irreversible modifications of the cell behaviour. The basic study of the cellular and molecular processes related to the irreversible modifications occuring particularly after sublethal stress, as described herein, could help to identify the pathways involved in age-related pathologies. [References: 50]