Apoptosis Remodeling in Immunosenescence: Implications for Strategies to Delay Ageing

Authors: De Martinis, Massimo; Franceschi, Claudio; Monti, Daniela; Ginaldi, Lia

Source: Current Medicinal Chemistry, Volume 14, Number 13, June 2007 , pp. 1389-1397(9)

Publisher: Bentham Science Publishers

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Abstract:

Immunosenescence is characterized by a peculiar remodeling of the immune system, mainly induced by lifelong antigenic burden and oxidative stress. Apoptosis or programmed cell death plays a central role in the ageing process. Both recurrent antigenic stimulations and oxidative metabolism by-products, impinging upon the immune system, modify the apoptotic capability of lymphocytes, driving immunosenescence. The apoptosis remodeling, in addition to inflamm-ageing, i.e. the upregulation of anti-stress responses and inflammatory cytokines, represents one of the major determinants of ageing rate and longevity, as well as of the most common age-related diseases. The cells of the immune system undergo two different kinds of apoptotic processes: activation-induced cell death (AICD), geared towards the elimination of unnecessary lymphocytes following clonal expansion, and damage-induced cell death (DICD), particularly important for preventing the onset of neoplastic proliferations. During senescence these apoptotic pathways are differentially modulated, with variable impacts on the ageing process. A correct modulation of apoptosis may be useful for prolonging the lifespan or at least reducing age-related degenerative, inflammatory and neoplastic diseases whose incidence increases with age. This review focuses on the role of AICD and DICD dysfunction in the ageing process and highlights emerging anti-ageing therapeutical strategies offered by apoptosis re-modulation. The challenge for the future is to identify factors and signals that regulate apoptotic processes and determine if selective apoptosis manipulation in specific lymphocyte subsets could preserve immune function in the elderly, contributing to successful ageing.

Keywords: Immunosenescence; apoptosis; therapeutic intervention

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986707780831122

Affiliations: Department of Internal Medicine and Public Health, University of L'Aquila, Coppito - L'Aquila, Italy.

Publication date: June 1, 2007

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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