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

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 (18–25 years; n = 9) and older (60–75 years; n = 10) healthy men undertook a 30-min cycling bout at 70% V O₂peak, with circulating T_ANG 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 T_ANG cells (mean ± SEM: 410 ± 81 vs. 784 ± 118 cells·μL, 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 × 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 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.