Cellular aging and the importance of energetic factors

The in vitro aging of human fibroblasts has become a classical model for studying cellular aging. This model was lately redefined by showing that these cells represent a stem cell system in which they progressively pass through seven morphotypes. Experimental data showed that external conditions that can be considered as stresses for the cells, can modulate the genome expression by speeding up the passage of the cells from one morphotype to the other. In this article, we will interpret these observations from the point of view of the thermodynamics of far from equilibrium open systems, which shows the importance of the production and the use of energy, both responsible for the generation of a given amount of entropy production. In stable systems like these cell morphotypes, such a production is constant but external stresses can prematurely destabilize the steady state of entropy production and, in doing so, accelerate the process of aging. It is also predicted that cells submitted to a stress will use part of their energy in response to the stress. Some experimental data in favor of such an interpretation have been obtained and more will be presented here that show that both cell death and accelerated cell aging under stress are modulated by the level of energy metabolism. All theoretical and experimental arguments presented in this article will show that cellular aging is related to stress and also to energy production through a very elaborate system of regulatory processes necessary for the cell to survive and to perform specific functions according to its differentiated state. This regulatory system also permits the cell to adapt its response according to the intensity of external as well as internal challenges and one of these responses will influence the cellular aging rate. © 1995.