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Older men display elevated levels of senescence-associated exercise-responsive CD28null angiogenic T cells compared
Mark Ross1, Lesley Ingram1, Guy Taylor2
1School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom.
Insights
Older adults have fewer angiogenic T cells (TANG), but a higher proportion are senescent (CD28null). Exercise increases TANG cells in older men, preferentially mobilizing senescent TANG cells, potentially impacting cardiovascular disease risk.
Area of Science:
- Immunology
- Gerontology
- Cardiovascular Science
Background:
- Aging is linked to increased cardiovascular disease (CVD) risk, partly due to endothelial dysfunction and reduced vascular repair.
- Angiogenic T cells (TANG), identified as CD31+ T cells, are crucial for vascular regeneration but decrease with age.
- Older populations exhibit elevated levels of senescent T cells, which show responsiveness to exercise.
Purpose of the Study:
- To investigate whether older adults have higher levels of circulating senescent (CD28null) TANG cells compared to younger individuals.
- To determine if these senescent TANG cells are more responsive to exercise than their non-senescent (CD28+) counterparts in older adults.
Main Methods:
- A cohort of young (18-25 years) and older (60-75 years) healthy men participated in a 30-minute cycling exercise at 70% V˙O2 peak.
- Circulating TANG cells (CD3+CD31+CD28+/null, including CD4+ and CD8+ subsets) were quantified using flow cytometry before, immediately after, and 1 hour post-exercise.
- Comparisons were made between age groups and between senescent (CD28null) and non-senescent (CD28+) TANG cell phenotypes.
Main Results:
- Older adults exhibited significantly lower basal levels of TANG cells compared to younger adults (410 ± 81 vs. 784 ± 118 cells·μL-1).
- A greater proportion of circulating TANG cells in older adults were senescent (CD28null) compared to younger individuals (26.26 ± 5.08% vs. 13.36 ± 2.62%).
- Exercise increased TANG cell counts in both groups, but in older men, it preferentially mobilized senescent CD8+ TANG cells (Δ74 ± 29 cells·μL-1) over non-senescent ones (Δ27 ± 15 cells·μL-1).
Conclusions:
- This study is the first to show that older adults have fewer circulating TANG cells, but a higher proportion of these are senescent (CD28null).
- Exercise preferentially mobilizes senescent TANG cells in older men, suggesting a unique response to physical activity.
- The reduced number of circulating TANG cells and increased senescent TANG cells in older adults may contribute to age-related cardiovascular disease risk.
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˙O2 peak, 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.
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