Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 129, Issue 11, Pages 656-664Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2008.09.004
Keywords
Horses; Aging; Proliferation; Apoptosis; Inflammatory cytokines
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Funding
- William Robert Mills endowment
- Jeffrey C. Hughes Foundation
- Gluck Equine Research Center
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A number of model systems have been employed to investigate age-associated changes in immune function. The purpose of the current study was to characterize senescent T cells and to investigate the inflamm-aging phenomenon both in vitro and in vivo using the old horse as a model. We examined whether decreased T cell proliferation induced by Con A is caused by increased apoptosis. We also utilized intracellular CFSE to analyze changes within each round of cell proliferation, in particular cytokine production. Intracellular staining with flow cytometry, RT-PCR, and ELISA were used to measure pro-inflammatory cytokines both in vitro and in vivo. While lymphocytes from old horses exhibit decreased proliferation, this is not the result of increased apoptosis. Instead, a larger percentage of the T cells remain in the parent generation and produce significant amounts of IFN gamma. Likewise, old horses have increased frequency of CD8(-)IFN gamma(+) T cells and TNF alpha producing cells. We also show that old horses have elevated levels of IL-1 beta, IL-15, IL-18 and TNF alpha gene expression in peripheral blood and significant levels of TNF alpha protein in serum, all characteristics of inflamm-aging. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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