Apoptosis remodeling in immunosenescence: Implications for strategies to delay ageing

Massimo De Martinis, Claudio Franceschi, Daniela Monti, Lia Ginaldi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1389-1397
Number of pages9
JournalCurrent Medicinal Chemistry
Volume14
Issue number13
DOIs
Publication statusPublished - Jun 2007

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Keywords

  • Apoptosis
  • Immunosenescence
  • Therapeutic intervention

ASJC Scopus subject areas

  • Organic Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

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