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Mismatch Repair System and Aging: Microsatellite Instability in Peripheral Blood Cells of the Elderly and in the T-cell Clone Longitudinal Model

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Handbook on Immunosenescence

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Abstract

Age-related accumulation of DNA damage in human T-cells has been well documented and could be associated with T-cell malfunctions. Therefore, an age-related reduction in DNA repair capacity of human lymphocytes may contribute to this phenomenon and play a key role in the modification of the immune response observed in the elderly. Because the Mismatch Repair system is the main postreplicative pathway for the correction of replication errors and few data suggest a possible alteration with age of this repair pathway, it is conceivable that, also in the immune system, age-related alterations of mismatch repair could contribute to the accumulation of genetic damage. This is particularly true for adaptive immune response, whose function depends on the ability of T-cells to undergo repetitive replications after antigenic challenge. The present chapter will focus on the role of the Mismatch Repair System that is recently emerging as a possible additional mechanism contributing to the accumulation of genetic instability during aging in peripheral blood cells. In vivo data at present available in the literature and results from studies on cloned human T lymphocytes cultured for different periods in vitro, as a model of immunosenescence, will be reviewed.

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  1. Laboratorio di Immunologia e Genetica, Istituto di Ricerca Codivilla-Putti, IOR, Via di Barbiano 1/10, 40136, Bologna, Italy

    Simona Neri & Erminia Mariani

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  1. Simona Neri
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  2. Erminia Mariani
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Editors and Affiliations

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, 1036 Rue Belvedere, J1H 4C4, Sherbrooke, Quebec, Canada

    Tamas Fulop

  2. Department of Experimental Pathalogy, CIG Interdepartmental Center “L. Galvani” University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, 4-6-22 Kohinato, Bunkyo-ku, Tokyo, 112-0006, Japan

    Katsuiku Hirokawa

  4. ZMF - Zentrum Med. Forschung Abt. Transplant./ Immunologie, University of Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany

    Graham Pawelec

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Neri, S., Mariani, E. (2009). Mismatch Repair System and Aging: Microsatellite Instability in Peripheral Blood Cells of the Elderly and in the T-cell Clone Longitudinal Model. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook on Immunosenescence. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9063-9_14

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