Many studies have reported that regular exercise confers health benefits and that, conversely, a sedentary lifestyle is a major risk factor for morbidity and mortality (particularly from cardiovascular disease). In recent years, researchers have begun to look more specifically at the immunological effects of exercise. The scientist Richard Simpson, formerly at Napier University in Edinburgh and now based at the University of Houston in Texas, has pioneered the exploration of the intersection between exercise and immune senescence. This research is potentially relevant to HIV infection because, as reported in some prior blog posts (see the immunosenescence category), senescent immune cells—particularly CD8 T cells—accumulate over time and may persist despite antiretroviral therapy. Simpson’s recent work suggests that exercise mobilizes senescent immune system cells from the tissues into the blood and increases their death by apoptosis; if confirmed this may offer both a more practical approach to addressing senescence than the idea of physically removing cells, and could also explain some of the positive contributions of exercise to healthy aging that have been described in the literature.
Exercise may also have a beneficial impact on inflammation, another problem common to both aging and HIV infection. In Nature Reviews Immunology, Mike Gleeson and colleagues from Loughborough University in the UK review the mechanisms by which exercise may reduce inflammation, and highlight some of the questions that remain to be answered about which mechanisms are most important in producing beneficial health outcomes.
Finally, in a paper in press at the Journal of the Association of Nurses in AIDS Care, Anella Yahiaoui and colleagues review the literature in an attempt to offer evidence-based exercise recommendations for older individuals with HIV. They conclude that:
“Combined moderate to vigorous aerobic and resistance exercise for 20-40 minutes, 3 times per week, is safe and effective in older adults and has many benefits to decrease symptom burden, decrease disease progression, and increase quality of life.”
Additional specifics are included in the paper. The authors also recommend the basic "Exercise Tips for Older Americans" offered on the website of the American Heart Association.
Brain Behav Immun. 2011 Jul 19. [Epub ahead of print]
Spielmann G, McFarlin BK, O'Connor DP, Smith PJ, Pircher H, Simpson RJ.
Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3855 Holman Street, Houston, TX 77204, USA; Biomedicine and Sports Science Research Group, School of Life Sciences, Edinburgh Napier University, 10 Colinton Road, Edinburgh, EH10 5DT, UK.
Senescent T-cells accumulate with age, lowering the naïve T-cell repertoire and increasing host infection risk. As this response is likely to be influenced by certain lifestyle factors, we examined the association between aerobic fitness (V˙O(2max)) and the age-related accumulation of senescent T-cells. Blood lymphocytes from 102 healthy males (18-61yr) were analyzed for KLRG1, CD57, CD28, CD45RA, CD45RO surface expression on CD4+ and CD8+ T-cells by 4-color flow cytometry. Advancing age (yr) was positively associated with the proportion (%) of senescent (KLRG1+/CD57+; KLRG1+/CD28-) CD4+ (B=1.00; 1.02) and CD8+ (B=0.429; 1.02) T-cells and inversely associated with naïve (KLRG1-/CD28+) CD4+ (B=-1.000) and CD8+ (B=-0.993) T-cells. V˙O(2max) was inversely associated with senescent CD4+ (B=-0.97) and CD8+ (B=-0.240). Strikingly, age was no longer associated with the proportions of senescent or naïve T-cells after adjusting for V˙O(2max), while the association between V˙O(2max) and these T-cell subsets withstood adjustment for age, BMI and percentage body fat. Ranking participants by age-adjusted V˙O(2max) revealed that the highest tertile had 17% more naïve CD8+ T-cells and 57% and 37% less senescent CD4+ and CD8+ T-cells, respectively, compared to the lowest tertile. V˙O(2max) was not associated with latent cytomegalovirus (CMV), Epstein-Barr virus (EBV) or herpes simplex virus-1 (HSV-1) infection, indicating that the moderating associations of V˙O(2max) were not confounded by persistent viral infections. This is the first study to show that aerobic fitness is associated with a lower age-related accumulation of senescent T-cells, highlighting the beneficial effects of maintaining a physically active lifestyle on the aging immune system.
Exerc Sport Sci Rev. 2011 Jan;39(1):23-33.
Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, Houston, TX 77204, USA.
Overcrowding the immune space with excess clones of viral-specific T cells causes the naïve T-cell repertoire to shrink, which increases infection susceptibility to novel pathogens. Physical exercise preferentially mobilizes senescent T cells from the peripheral tissues into the blood, which might facilitate their subsequent apoptosis and create "vacant space" for newly functional T cells to occupy and expand the naïve T-cell repertoire.
Exerc Immunol Rev. 2010;16:40-55.
Simpson RJ, Cosgrove C, Chee MM, McFarlin BK, Bartlett DB, Spielmann G, O'Connor DP, Pircher H, Shiels PG.
Laboratory of Integrated Physiology, Department of Health and Human Performance, University of Houston, 3855 Holman Street, Houston, Texas 77204, USA.
Acute bouts of aerobic exercise are known to mobilize antigen-experienced CD8+ T-cells expressing the cell surface marker of senescence, KLRG1, into the blood. It is not known; however if this is due to a selective mobilization of terminally differentiated T-cells (i.e., KLRG1 +/CD28-/CD57+) or a population of effector memory T-cells (i.e., KLRG1+/CD28+/CD57-) that have not reached terminal differentiation. The aim of this study was to further characterize KLRG1 + T-cells mobilized by acute exercise by assessing the co-expression of KLRG1 with CD28 or CD57 and to determine telomere lengths in the CD4+ and CD8+ T-cell subsets. Nine moderately trained male subjects completed an exhaustive treadmill running protocol at 80%. Blood lymphocytes isolated before, immediately after and 1h after exercise were labelled with antibodies against KLRG1, CD28 or CD57, CD4 or CD8 and CD3 for 4-color flow cytometry analysis. Telomere lengths in CD3+, CD4+ and CD8+ T-cells were determined using Q-PCR. The relative proportion of KLRG1 + cells among the CD8+ T-cells increased by 40% immediately after exercise, returning to baseline 1h later. This was due to a mobilization of KLRG1+/CD28- (61% increase), KLRG1+/CD57+ (56% increase) and to a lesser extent, KLRG1+/CD57- cells (24% increase). Telomeres in CD8+ T-cells displayed an increased relative length immediately after exercise, whereas no change occurred for CD4+ or the overall CD3+ T-cells. In conclusion, the increased frequency of KLRG1 +/CD8+ T-cells in blood after acute exercise is predominantly due to a selective mobilization of terminally differentiated T-cells. The increased relative telomere length in CD8+ T-cells after exercise might indicate that KLRG1+ cells mobilized by exercise are under stress or aberrant signaling-induced senescence (STASIS). We postulate that a frequent mobilization of these cells by acute exercise might eventually allow naïve T-cells to occupy the "vacant" immune space and increase the naïve T-cell repertoire.
Nat Rev Immunol. 2011 Aug 5. doi: 10.1038/nri3041. [Epub ahead of print]
Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA.
Inflammation, Exercise and Metabolism Research Group, School of Sport, Exercise and Health Sciences, Loughborough University, Ashby Road, Loughborough, Leicestershire LE11 3TU, UK.
Regular exercise reduces the risk of chronic metabolic and cardiorespiratory diseases, in part because exercise exerts anti-inflammatory effects. However, these effects are also likely to be responsible for the suppressed immunity that makes elite athletes more susceptible to infections. The anti-inflammatory effects of regular exercise may be mediated via both a reduction in visceral fat mass (with a subsequent decreased release of adipokines) and the induction of an anti-inflammatory environment with each bout of exercise. In this Review, we focus on the known mechanisms by which exercise - both acute and chronic - exerts its anti-inflammatory effects, and we discuss the implications of these effects for the prevention and treatment of disease.
J Assoc Nurses AIDS Care. 2011 Jul 29. [Epub ahead of print]
Yahiaoui A, McGough EL, Voss JG.
Advances in antiretroviral therapy (ART) have decreased HIV-related morbidity and mortality and contributed to rapidly increasing numbers of older people living with HIV. Successful management of ART-related side effects (metabolic syndrome) and age-related comorbidities (frailty) are major challenges for patients and providers. Exercise has proven beneficial for younger HIV-infected patients, but we know little about which exercise regimens to recommend to the elderly. Our goal was to develop age-appropriate, evidence-based exercise recommendations for older HIV-infected adults (age > 50). We reviewed randomized controlled trials on the effects of physical exercise for: (a) HIV-infected young adults, (b) frail older adults, and (c) elderly individuals with metabolic syndrome. We recommend a combination of endurance and resistance exercises 3 times per week for at least 6 weeks to improve cardiovascular, metabolic, and muscle function. Further research is warranted to study the benefits and risks of physical exercise in older HIV-infected patients.