The controversial relationship between immunosenescence and apoptosis.

"Programmed cell death or apoptosis is a complex process that allows cells to die in a controlled fashion, On the basis of the nature of the apoptosis-inducing stimuli, an activation-induced apoptosis and a damage-induced apoptosis can be identified. The balance between removal of damaged cells via apoptosis and proliferation of needed cells is a central process in body homeostasis and its derangement is involved in many physiopathological conditions, including ageing and immunosenescence. Programmed cell death is a key regulator of clonotypic diversity generation during lymphocyte ontogenesis and is essential for the proper function of the immune system, controlling lymphocyte activation and clonal expansion following antigenic stimulation. Moreover, apoptosis is markedly involved in many changes characteristic of immunosenescence, such as thymic involution, alteration of T-cell repertoire, accumulation of memory\/effector cells, osteoporosis, autoimmunity and cancer. Despite the increasing data on age-related changes in cell-death phenomena, the impact of apoptosis remodelling in the ageing process and its exact role in the pathogenesis of age-related diseases are still controversal. The remodulation of apoptotic processes observed in the elderly could exert variable impacts on ageing and human health. Immunosenescence, i.e. the ageing of the immune system observed in the elderly, is characterized by a peculiar remodelling of programmed cell death phenomena. On the other hand apoptosis plays a central role in driving the ageing process. Both recurrent antigenic stimulations and oxidative metabolism byproducts, impinging upon the immune system, modify the apoptotic capability of lymphocytes, driving immunosenescence. In addition to the upregulation of anti-stress responses and inflammatory cytokines (inflammageing), the subtle remodelling apoptotic pathways in the elderly contributes to the phenotypic and functional characteristics of the aged immune system, representing one of the major determinants of ageing rate and longevity, as well as of the most common age-related diseases. Understanding of apoptosis signalling mechanisms in more details is therefore essential for the identification of multiple potential targets to inhibit or enhance apoptosis in different cell subsets. A correct modulation of apoptosis in specific lymphocyte subsets could preserve immune function in the elderly and may be useful for prolonging the lifespan and reducing age-related degenerative, inflammatory and neoplastic diseases, contributing to successful ageing.. . "