<b><i>Background:</i></b> Highly differentiated, senescent lymphocytes are pro-inflammatory and contribute to age-related systemic inflammation, called inflammageing. There are several reports of acute changes in senescent lymphocyte counts post exercise, which potentially have consequences for systemic inflammation. However, there is little consensus since the studies differ with respect to participants, exercise protocols, cellular markers assessed, and the time point of assessment post exercise. <b><i>Objective:</i></b> We performed a systematic review and meta-analysis to assess the impact of exercise on senescent lymphocyte counts in blood immediately, 1 h and 2 h post exercise. <b><i>Methods:</i></b> The search was performed in PubMed (MEDLINE), Web of Science, Embase, Scopus, and Cochrane, on January 11, 2021. The 13 studies selected tested aerobic exercise effects, mainly in young men. They assessed the counts of lymphocytes (CD4 T cells, CD8 T cells, and NK cells), with the following immune cell marker combinations: KLRG1+, CD57+ (only NK cells), EMRA T cells (CD45RA+CCR7−CD28−CD27−), CD28−CD27−, KLRG1+CD28−, and CD28−. Independent extraction of articles was done by 2 researchers. <b><i>Results:</i></b> Standardized mean difference (SMD) and 95% confidence interval between baseline and post exercise showed significant increase (SMD >0.9, <i>p</i> < 0.003) in all types of senescent lymphocytes counts immediately post exercise. At 1 h post exercise, senescent CD4 T cells returned to baseline values (<i>p</i> = 0.74), CD8 T cells were reduced (−0.26 [−0.41; −0.11], <i>p</i> = 0.001), and senescent NK cells were raised (0.62 [0.14; 1.10], <i>p</i> = 0.01) above baseline. By 2 h post exercise, senescent CD4 T cells were reduced (−0.94 [−1.40; −0.48], <i>p</i> < 0.001), CD8 T cells remained below baseline (−0.53 [−1.04; −0.009], <i>p</i> = 0.04), and NK cells had returned to baseline values (−0.29 [−0.64; 0.07], <i>p</i> = 0.11). The main determinants of heterogeneity between studies were cytomegalovirus (CMV) serostatus and the characteristics of exercise protocols. CMV+ individuals had a higher immediate lymphocytosis and 1 h post lymphopenia than CMV− individuals. Exercise performed at higher intensities and shorter durations led to higher magnitude of change in senescent lymphocyte counts at all time-points. <b><i>Conclusion:</i></b> The differing effects of exercise on senescent NK cells and CD4 and CD8 T cells suggest differing susceptibility to factors modulating lymphocyte extravasation such as adrenaline and exercise intensity.
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