Older men display elevated levels of senescence-associated exercise-responsive CD28(null) angiogenic T cells compared with younger men

Abstract

Aging is associated with elevated cardiovascular disease risk. As a result of aging, endothelial dysfunction develops, partly due to a reduction in vascular regenerative ability. CD31(+) T cells (angiogenic T cells; T-ANG) possess highly angiogenic capabilities; however, these cells are significantly reduced in older populations. In addition, older populations possess significantly higher senescent and highly differentiated T-cell levels in circulation, and these are reported to be highly exercise responsive. We investigated whether older adults display greater levels of circulating senescent (CD28(null)) T-ANG cells and whether these cells were more exercise responsive than CD28(+) T-ANG cells. Young (18-25years; n=9) and older (60-75years; n=10) healthy men undertook a 30-min cycling bout at 70% VO(2)peak, with circulating T-ANG cells (CD3(+)CD31(+)CD28(+/null); including CD4(+) and CD8(+) subsets) measured preexercise, postexercise, and 1h post exercise by flow cytometry. Older adults displayed reduced basal levels of T-ANG cells (mean +/- SEM: 410 +/- 81 vs. 784 +/- 118cells<bold>L</bold>, P=0.017), despite a greater proportion of these cells being CD28(null) (26.26 +/- 5.08 vs. 13.36 +/- 2.62%, P=0.044). Exercise significantly increased the circulating number of T-ANG cells in both young and older men. However, in older men alone, exercise preferentially mobilized CD28(null) CD8(+)T(ANG) cells compared with CD28(+) T-ANG cells (time x phenotype interaction: P=0.022; 74 +/- 29 vs. 27 +/- 15cells<bold>L</bold>, P=0.059), with no such difference observed between these phenotypes in the young population. In conclusion, this is the first study to demonstrate that despite observing lower circulating numbers of T-ANG cells, older adults display greater levels of senescent T-ANG cells in comparison with younger individuals, and these cells are more exercise responsive than CD28(+) T-ANG cells. Lower number of circulating T-ANG and greater levels of senescent-associated CD28(null) T-ANG may contribute to greater CVD risk with advancing age.