Human aging and CD31⁺T-cell number, migration, apoptotic susceptibility, and telomere length

Abstract

Kushner EJ, Weil BR, MacEneaney OJ, Morgan RG, Mestek ML, Van Guilder GP, Diehl KJ, Stauffer BL, DeSouza CA. Human aging and CD31 ϩ T-cell number, migration, apoptotic susceptibility, and telomere length. J Appl Physiol 109: 1756 -1761. First published September 23, 2010 doi:10.1152/japplphysiol.00601.2010.-CD31 ϩ T cells, or so-called "angiogenic T cells," have been shown to demonstrate vasculoprotective and neovasculogenic qualities. The influence of age on CD31 ϩ T-cell number and function is unclear. We tested the hypothesis that circulating CD31 ϩ T-cell number and migratory capacity are reduced, apoptotic susceptibility is heightened, and telomere length is shortened with advancing age in adult humans. Thirtysix healthy, sedentary men were studied: 12 young (25 Ϯ 1 yr), 12 middle aged (46 Ϯ 1 yr), and 12 older (64 Ϯ 2 yr). CD31 ϩ T cells were isolated from peripheral blood samples by magnetic-activated cell sorting. The number of circulating CD31 ϩ T cells (fluorescenceactivated cell sorting analysis) was lower (P Ͻ 0.01) in older (24% of CD3 ϩ cells) compared with middle-aged (38% of CD3 ϩ cells) and young (40% of CD3 ϩ cells) men. Migration (Boyden chamber) to both VEGF and stromal cell-derived factor-1␣ was markedly blunted (P Ͻ 0.05) in cells harvested from middle-aged [306.1 Ϯ 45 and 305.6 Ϯ 46 arbitrary units (AU), respectively] and older (231 Ϯ 65 and 235 Ϯ 62 AU, respectively) compared with young (525 Ϯ 60 and 570 Ϯ 62 AU, respectively) men. CD31 ϩ T cells from middle-aged and older men demonstrated greater apoptotic susceptibility, as staurosporine-stimulated intracellular caspase-3 activation was ϳ40% higher (P Ͻ 0.05) than young. There was a progressive age-related decline in CD31 ϩ T-cell telomere length (young: 10,706 Ϯ 220 bp; middle-aged: 10,179 Ϯ 251 bp; and older: 9,324 Ϯ 192 bp). Numerical and functional impairments in this unique T-cell subpopulation may contribute to diminished angiogenic potential and greater cardiovascular risk with advancing age. age; apoptosis; vascular CD31 OR PLATELET/ENDOTHELIAL cell adhesion molecule (PECAM) is a glycoprotein present on the surface of immune cells including platelets, monocytes, and granulocytes (4, 38). The CD31 receptor globulin is composed of six extracellular immunoglobulin repeats followed by a transmembrane domain and two cytosolic immunoreceptor tyrosine inhibitory motifs that carry a diverse array of signaling consequences known to be involved in cell phenotype determination, gene expression, and cell cycle (29,30,36). The unique structural homology of CD31's extracellular region is responsible for facilitating numerous heterophilic and homophilic binding interactions between differing vascular tissues (10, 16). For example, CD31 is highly expressed in the border junctions of endothelial cells where it plays a role in endothelial cell motility and regulating leukocyte transendothelial migration (31). In CD31 knockout mice, endothelial cell motility and filopodia formation as well as neovascularization are markedly impaired (5).Recently,...

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