No abstract

Aging is associated with a dysfunctional endothelial phenotype as well as reduced angiogenic capabilities. Exercise exerts beneficial effects on the cardiovascular system, possibly by increasing/maintaining the number and/or function of circulating angiogenic cells (CACs), which are known to decline with age. However, the relationship between cardiorespiratory fitness (CRF) and age-related changes in the frequency of CACs, as well as the exercise-induced responsiveness of CACs in older individuals, has not yet been determined. One-hundred seven healthy male volunteers, aged 18-75 yr, participated in study 1. CRF was estimated using a submaximal cycling ergometer test. Circulating endothelial progenitor cells (EPCs), angiogenic T cells (T), and their chemokine (C-X-C motif) receptor 4 (CXCR4) cell surface receptor expression were enumerated by flow cytometry using peripheral blood samples obtained under resting conditions before the exercise test. In study 2, 17 healthy men (8 young men, 18-25 yr; 9 older men, 60-75 yr) were recruited, and these participants undertook a 30-min cycling exercise bout at 70% maximal O consumption, with CACs enumerated before and immediately after exercise. Age was inversely associated with both CD34 progenitor cells ( r = -0.140, P = 0.000) and T ( r = -0.176, P = 0.000) cells as well as CXCR4-expressing CACs (CD34: r = -0.167, P = 0.000; EPCs: r = -0.098, P = 0.001; T: r = -0.053, P = 0.015). However, after correcting for age, CRF had no relationship with either CAC subset. In addition, older individuals displayed attenuated exercise-induced increases in CD34 progenitor cells, T, CD4, T, and CD8CXCR4 T cells. Older men display lower CAC levels, which may contribute to increased risk of cardiovascular disease, and older adults display an impaired exercise-induced responsiveness of these cells. NEW & NOTEWORTHY Older adults display lower circulating progenitor cell and angiogenic T cell counts compared with younger individuals independently of cardiometabolic risk factors and cardiorespiratory fitness. Older adults also display impaired exercise-induced mobilization of these vasculogenic cells.

No 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% trueV˙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.

What is the central question of the study? Are CD31 angiogenic T (T ) cells preferentially mobilized in response to acute exercise? What is the main finding and its importance? Our study reveals that T cells are redistributed into the circulation in response to acute strenuous exercise, but to a lesser extent than CD31 T cells. Of the T cells mobilized, T cells expressing CXCR4 show greater redistribution compared with CXCR4 T cells. Stromal-derived factor 1-α does not appear to play a role in the redistribution of T cells expressing CXCR4. The results suggest that a single bout of strenuous exercise might provide a short vasculogenic window, which could benefit the vascular system by redistributing CD31 T cells. CD31 T cells have been documented to possess vasculogenic properties and have been termed 'angiogenic T cells' (T cells). No study to date has fully characterized the effect of acute exercise on T cells. Twelve male participants aged 24-45 years undertook a running 10 km time trial, with peripheral blood samples taken before, immediately after and 1 h postexercise for quantification of T cells and subsequent CXCR4 cell surface expression by flow cytometry. The T cells demonstrated a 102% increase in number in the peripheral circulation immediately postexercise compared with pre-exercise levels, followed by a large egress (50%) from the circulation in total T cells 1 h postexercise. This was due to changes in both CD4 and CD8 T cells, with CD8 T cells displaying greater ingress (123%) and egress (52%) compared with CD4 T cells (ingress, 83%; egress, 37%). The cell surface expression intensity of CXCR4 was affected only on CD8 T cells, with a significant increase in cell surface expression immediately postexercise versus pre-exercise levels. The CD31 T cells displayed greater redistribution than CD31 T cells (119 versus 102%). CXCR4-expressing T cells showed greater response to acute exercise than CXCR4 cells, which was accompanied by large changes in CXCR4 ligand SDF-1α. The results show that acute exercise increases T cells in the circulation in response to an acute exercise stressor. Additionally, CXCR4 cell surface expression appears to be increased in response to exercise, which may result from the direct upregulation of CXCR4 on the T-cell surface or could be due to CD31 T cells being redistributed into the blood expressing greater levels of CXCR4.