Apoptosis and aging: breast cells and apoptosis

The major events involved in tissue homeostasis are proliferation, differentiation and apoptosis. Senescence is a non-dividing state of the cell, usually associated with terminal differentiation, and preceding cell death. The three pathways result in suppression of cell proliferation. Apoptosis during aging can contribute to the elimination of damaged, dysfunctional cells, which can then be replaced by cell proliferation, thereby maintaining homeostasis. However, in some models (fibroblasts, thymocytes/lymphocytes), aging is associated with a decrease in apoptosis, and lower sensitivity of the potent anti-apoptotic gene, bcl-2, to pro-apoptotic stimuli [1]. Aging is also related to the loss of telomerases. Normal human diploid cells have a limited ability to proliferate; this is called the Hayflick limit; when the cells stop proliferating, senescence occurs. However senescence is associated with strong metabolic activities that persist a long time before cell death. This state is thus related to terminal differentiation. In case of tumorigenesis, however, cells continue to proliferate due to a loss of function of tumor supressor genes such as p53 (see below) or to a gain of function of some growth factors or early nuclear genes. There are some molecular links between apoptosis, senescence and terminal differentiation. * Corresponding author. Tel.: +33-1-42348099; fax: +331-43298766.