Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

Back

Apoptosis Remodeling in Immunosenescence: Implications for Strategies to Delay Ageing

Author(s): Massimo De Martinis, Claudio Franceschi, Daniela Monti and Lia Ginaldi

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

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

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

VOLUME: 14
ISSUE: 13
Page: [1389 - 1397]
Pages: 9
DOI: 10.2174/092986707780831122
Price: $58