Older men display elevated levels of senescence-associated exercise-responsive CD28^nullangiogenic 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% 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.

Circulating angiogenic cell response to sprint interval and continuous exercise

“…The results of the present study are similar to those observed following a 10 km treadmill time-trial (Ross et al 2016), where increases in circulating CD3 + CD31 + , CD8 + CD31 + and CD4 + CD31 + cells were reported immediately post-exercise with values back to pre-exercise levels at 1 h post-exercise. Two other studies (Ross et al 2018a;Ross et al 2018b) have reported that the response of these TANG cells to continuous exercise is age-dependent, with an impaired ingress and egress of these cells in older participants. The 45 min duration of exercise in CONTEX is similar to that in the 10 km timetrial.…”

“…Increases in CAC were evident immediately post-exercise with counts typically back to pre-exercise values at the 2 h timepoint. Exercise also elicited a qualitative change in CAC, evidenced by the increase in CXCR4 expression on TANG at the 24 h timepoint, To date, only a limited number of studies (Lansford et al 2016;Ross et al 2018a;Ross et al 2016;Ross et al 2018b;Shill et al 2016) examining the effects of acute exercise on circulating TANG have been undertaken. The results of the present study are similar to those observed following a 10 km treadmill time-trial (Ross et al 2016), where increases in circulating CD3 + CD31 + , CD8 + CD31 + and CD4 + CD31 + cells were reported immediately post-exercise with values back to pre-exercise levels at 1 h post-exercise.…”

“…The preferential mobilisation of exercise responsive lymphocyte and monocyte subsets appears to be dependent on β2 adrenergic signalling (Graff et al 2018), with preferential mobilisation of cytotoxic CD8 + over CD4 + T lymphocytes and pro-inflammatory CD16 + over CD14 + monocytes (Dimitrov et al 2010). Less clear are the factors explaining the preferential mobilisation of the non-angiogenic CD31cells but this may relate to T cell differentiation status (Ross et al 2018a;Simpson et al 2007). Regardless of these preferential release patterns, it should be noted that all angiogenic subsets were increased post-exercise in SPRINT by between 38% and 145%.…”

“…A 10 km treadmill time trial increased circulating CD3 + CD31 + counts immediately post-exercise in recreationally active men with a return to baseline levels at 1-hour post exercise (Ross et al 2016). Increases have also been demonstrated in older men following 30 min of continuous moderate to vigorous exercise (Ross et al 2018a;Ross et al 2018b). Continuous exercise may also alter CAC surface marker and gene expression (Lansford et al 2016).…”

Immunosenescence Study of T Cells: A Systematic Review

“…Only 28% of the studies did not describe whether the measurement was done on frozen or fresh cells ( 15 , 22 , 23 , 26 , 28 – 31 , 49 , 50 ); 33% of the articles did not report the number of cells used in each experiment ( 15 , 17 , 18 , 20 , 22 , 24 – 26 , 28 , 31 , 35 , 36 ), while only 31% clearly described the antibodies with fluorochrome and clone used ( 15 , 21 , 22 , 28 , 31 , 39 , 41 , 43 , 44 , 46 , 48 ). The factor with the highest risk of bias is the clarity in the presentation of the results, since only 25% of the studies reported measures of central tendency ( 16 , 27 , 33 , 37 , 41 , 42 , 47 , 48 , 50 ). Most of the studies reported only the graphics and p-value, thus making it difficult to quantitatively compare results and rate evidence.…”