Lower resting and exercise-induced circulating angiogenic progenitors and angiogenic T cells in older men

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.

Older men display elevated levels of senescence-associated exercise-responsive CD28nullangiogenic T cells compared with younger men

“…Previous studies have also observed redistribution of T ANG cells into the circulation with a single bout of exercise, in both young and older men (Ross et al. , ). This T‐cell response is not uncommon, as many T‐cell subsets increase in circulation in response to acute exercise stimuli, such as naive T cells (T NAÏVE ), cytotoxic T cells (T CYTOTOXIC ), and regulatory T cells (T REG ) (Brown et al.…”

“…Individual's peak oxygen consumption (O 2 peak) was quantified as described previously (Ross et al. ). Briefly, participants undertook an incremental graded exercise test to exhaustion on a cycle ergometer (Lode Corival, Lode, the Netherlands) using online breath‐by‐breath gas analysis (Metalyzer 3B, Cortex, Germany).…”

“…Recently, we have been able to demonstrate that older adults also display significantly lower levels of these angiogenic T cells (T ANG ) than younger gender‐matched counterparts (Ross et al. ). These cells are thought to act in a different manner to EPCs, where they most likely promote endothelial regeneration and angiogenesis in a paracrine manner via the secretion of angiogenic factors VEGF and IL‐8 (Hur et al.…”

“…; Ross et al. ), and reduced circulating number of EPCs in older individuals is highly predictive of mortality (Lu et al. ; Samman Tahhan et al.…”

“…; Ross et al. , ), which may offer a vasculogenic window of adaptation. Previous studies have also observed redistribution of T ANG cells into the circulation with a single bout of exercise, in both young and older men (Ross et al.…”