Cell proliferation and apoptosis in the immune system in the elderly

Loss of the cell proliferative capability and involution of tissues and org ans are among the most important phenomena that characterize the aging proc ess. Some of the aged-linked immune dysfunctions could be partly due to a d ysregulation of apoptotic processes and to a lower responsiveness of aged l ymphoid cells to activation and proliferation signals. The main changes in proliferative activity and cell death during aging and their impact on the process of immunosenescence are discussed. In fact, a very important functi on that has been suggested to deteriorate with age and to play a major role in the aging process is the capability of cells from aged subjects to resp ond to mitogenic stimuli and, consequently, to undergo cell proliferation. However, the cellular activation processes are very complex and the prolife rative responses can follow different interconnected signal transduction pa thways, and only some of them appear to be modified during age. Moreover, c ell growth, immunosenescence, and longevity are strictly interconnected and deeply related to programmed cell death or apoptosis. The cellular equilib rium between cell survival and proliferation, on the one hand, and programm ed cell death, on the other hand, seems to be unbalanced with advancing age , although in each type of immune cell it could be differentially modulated , resulting in a variety of clinicopathological consequences. Thus, cell, p roliferation and cell death are two physiologically active phenomena closel y linked and regulated and a failure of these mechanisms determines profoun d dysregulations of cell homeostasis with major consequences in immune func tioning and the onset of autoimmune diseases and cancer, whose incidence ap pears to be increased in the elderly.