Older men display elevated levels of senescence-associated exercise-responsive CD28null 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; TANG) 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 (CD28null) TANG cells and whether these cells were more exercise responsive than CD28+ TANG cells. Young (18–25 years; n = 9) and older (60–75 years; n = 10) healthy men undertook a 30-min cycling bout at 70% V O2peak, with circulating TANG cells (CD3+CD31+CD28+/null; including CD4+ and CD8+ subsets) measured preexercise, postexercise, and 1 h post exercise by flow cytometry. Older adults displayed reduced basal levels of TANG cells (mean ± SEM: 410 ± 81 vs. 784 ± 118 cells·μL, P = 0.017), despite a greater proportion of these cells being CD28null (26.26 ± 5.08 vs. 13.36 ± 2.62%, P = 0.044). Exercise significantly increased the circulating number of TANG cells in both young and older men. However, in older men alone, exercise preferentially mobilized CD28null CD8+ TANG cells compared with CD28+ TANG cells (time × phenotype interaction: P = 0.022; Δ74 ± 29 vs. Δ27 ± 15 cells·μL, 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 TANG cells, older adults display greater levels of senescent TANG cells in comparison with younger individuals, and these cells are more exercise responsive than CD28+ TANG cells. Lower number of circulating TANG and greater levels of senescent-associated CD28null TANG may contribute to greater CVD risk with advancing age.