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Effect of zinc ions on apoptosis in PBMCs from healthy aged subjects

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Abstract

Immunosenescence features, such as thymic involution, alteration of T-cell repertoire, autoimmunity and accumulation of memory/effector T cells, may be the result, at least in part, of a zinc deficiency, which is often observed during ageing. Zinc, as essential trace element, affects the immune system function and it is an important regulator of apoptosis of immune cells. In this study we addressed the question whether zinc supplementation in vitro at physiological doses can affect spontaneous and oxidative stress-induced apoptosis in peripheral blood mononuclear cells from subjects of three different age groups: young (mean age 28 years), old (mean age 72 years) and nonagenarians. We studied different parameters related to apoptosis (phosphatydilserine exposure, mitochondrial membrane potential, caspase 3 cleavage) and we found that zinc, while decreasing spontaneous apoptosis, can increase oxidative stress-induced apoptosis in an age-related fashion, being this effect more evident in nonagenarians than in old or young subjects. In particular, zinc can increase late apoptosis/necrosis, a phenomenon that could trigger unnecessary inflammation in vivo. We surmise that these age-associated alterations in susceptibility to apoptosis may be due to a different effect of zinc on T cell subsets, that are altered in very old people, and finally that the zinc deficiency, which is often observed in aged subjects, could be a compensatory mechanism to counteract the inflammatory status of the elderly.

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Acknowledgements

This work was supported by: EU Project “ZINCAGE” 6th FP, Contract no. FOOD-CT-2003-506850, and MIUR (PRIN 2004) Grant to DM; EU Projects “GEHA – Genetics of Healthy Aging” FP6-503270 Grant; the PRRIITT program of the Emilia-Romagna Region (and Fondi Strutturali Obiettivo 2) grant to CF; Italian Ministry of Health (Ricerca Finalizzata “Markers genetici di sindrome coronaria acuta e valutazione della L-arginina nella prevenzione di eventi ischemici”) Grant to DM and CF; University of Bologna Ricerca Fondamentale Orientata (RFO 2005), and Roberto and Cornelia Pallotti Legacy for Cancer Research Grants to CF and SS.

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Correspondence to D. Monti.

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Presented at the ZincAge Conference, Madrid, February 10–13, 2006.

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Ostan, R., Alberti, S., Bucci, L. et al. Effect of zinc ions on apoptosis in PBMCs from healthy aged subjects. Biogerontology 7, 437–447 (2006). https://doi.org/10.1007/s10522-006-9059-1

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