A Greater Vo2max Is Associated With A Reduced Frequency Of Senescent Blood T-cells In Middle-aged But Not Younger Men

Abstract

The clonal expansion of T-lymphocytes in response to an antigenic stimulus is an essential process of adaptive immunity. Chromosome telomeres become progressively eroded with each round of cell division, eventually leading to replicative senescence. T-lymphocytes with a senescent phenotype are known to accumulate with age, increasing infection risk in middle-aged and elderly individuals. A sedentary lifestyle is associated with shortened telomeres in peripheral blood leukocytes, but the influence of regular exercise on the frequency of T-cells with a senescent phenotype in young and older adults is not known. PURPOSE: To examine the impact of estimated VO2max on the frequency of senescent blood T-cells in young and middle-aged men. METHODS: Twenty young (Y; age: 23.4 ± 3; BMI: 24.6 ± 3) and 20 middle-aged (O; age: 54 ± 3.6; BMI: 26.4 ± 3.4) healthy males provided a fasted resting blood sample, completed an assessment of percentage body fat and a physical activity status questionnaire designed to estimate VO2max. Y and O subjects were then divided into Hi and Lo VO2max groups (VO2max; Y: 51.2 ± 4.4 vs 42.6 ± 2.2 ml·kg-1·min-1; O: 38.7 ± 3.3 vs 29.5 ± 1.3 ml·kg-1·min-1) with n=10 in each group. Isolated lymphocytes were assessed for cell surface expression of senescence (KLRG1+, CD28-, CD57+), naïve (CD45RA+) and memory (CD45RO+) T-cell markers on CD3+ T-cells, CD4+ T-cells and CD8+ T-cells using four-colour flow cytometry. Differences in T-cell phenotype among the 4-groups was analysed by one-way ANOVA. RESULTS: O had a greater proportion of KLRG1+, CD57+, CD28, KLRG1+/CD57+ and CD45RA-/CD45RO+ CD8+ T-cells than Y, regardless of estimated VO2max. No differences in senescent phenotypes were found between the Hi and Lo VO2max groups in Y. In contrast, the Hi VO2max group in O had a significantly lower frequency of CD4+ and CD8+ T-cells expressing KLRG1+ (CD4: 58%; CD8: 23% less), CD57+ (CD4: 71%; CD8: 20% less), CD28- (CD4: 91%; CD8: 24% less), KLRG1+/CD57+ (CD4: 89%; CD8: 26% less) and CD45RA-/CD45RO+ (CD4: 20% less), in comparison to the Lo VO2max group in O. CONCLUSION: A higher estimated VO2max is associated with a lowered frequency of senescent and memory CD4+ and CD8+ T-cells in middle-aged but not younger men. These findings highlight the beneficial effects of regular physical activity on cellular immunity during ageing.