Vigorous Physical Activity and the Length of Telomeres Across Levels of BMI in 4,458 U.S. Adults

Telomere length is an index of cellular aging. Longer telomeres are predictive of longer life. Healthy lifestyles are associated with longer telomeres. PURPOSE: This study focused on the relationship between time spent in vigorous physical activity (PA) and leukocyte telomere length (LTL) in 4,458 randomly selected U.S. adults, 20-69 years old. METHODS: The association was studied using data collected as part of the National Health and Nutrition Examination Survey (NHANES) and a cross-sectional design. Vigorous physical activity was indexed by calculating total time spent jogging or running per week (Jog/Run/Wk). Weekly jog/run time was calculated by multiplying days of jog/run per week by minutes per session. From the total, 3 categories were formed: None, Some, and Met Guidelines. Adults who jogged or ran more than 10 min/wk but less than 75 min/wk fit into the Some category. Adults who jog/ran 75 min/wk or more, and therefore met or exceeded the U.S. PA guidelines, were labeled, Met Guidelines. Participation in 47 other forms of PA was also calculated based on time spent in other PAs. Data were analyzed using one-way ANOVA. Partial correlation was used to adjust for differences in potential mediating factors, including demographic (age, sex, race, and economic status) and lifestyle factors (smoking pack years, BMI, participation in PA other than jog/run/wk, diabetes status, and cardiovascular disease status. RESULTS: In the total sample, after adjusting for all the potential covariates, mean LTL differed across the 3 jog/run/wk categories (F=4.1, P=0.0272). Specifically, adults who met the guidelines via jogging or running had longer telomeres than those who did not perform regular PA (None). With the sample delimited to normal weight adults only, there was no relationship between jog/run/wk and LTL (F=1.0, P=0.3774). However, focusing on adults with overweight only, the association was significant (F=3.9, P=0.0327). Adults who met the guidelines via jog/run had longer telomeres than sedentary adults. With the sample delimited to adults with obesity only, there were no differences in LTL across the 3 levels of jog/run/wk (F=0.8, P=0.4529). CONCLUSION: Jogging/running is predictive of adults with longer telomeres, but only among overweight adults, not in adults with normal weight or obesity

Time Spent Jogging/Running and Telomere Length in 5805 U.S. Adults

A scientifically accepted measure of biological aging is the length of telomeres. Telomeres shorten with each year of life. Although age is the primary driving force, lifestyle can also have a substantial effect on telomere length. PURPOSE: The aim of this study was to investigate the degree to which minutes spent jogging or running per week accounted for differences in leukocyte telomere length (LTL) in a randomly selected sample of 5805 U.S. adults. METHODS: A cross-sectional design was employed using data from the National Health and Nutrition Examination Survey (NHANES) and findings are generalizable to the U.S. adult population. Time spent jogging and/or running, both vigorous physical activities (PA), was compiled from duration and frequency measures reported by each participant. NHANES used the quantitative polymerase chain reaction technique to quantify LTL. Multiple regression was performed using SAS software to interpret the data. Partial correlation was used to control for potential confounders. RESULTS: Telomere lengths were 15.6 base pairs shorter for every year of chronological age (F=414.3. p\u3c0.0001). Weekly PA was divided into 3 categories: 1) No regular PA, 2) Some jogging/running, but less than the minimum recommendation of at least 75 min/wk for vigorous PA, and 3) ≥ 75 min/wk of jogging/running. After controlling for age, sex, income, and race, telomere lengths differed across the three categories (F=5.8, P=0.0074). Specifically, adults in category 3 exhibited significantly longer telomeres, 5999 base pairs (bp), than those not engaging in any regular PA (5799 bp). After adjusting for smoking, BMI, PA minutes other than jogging/running, diabetes, and heart disease, along with age, sex, income, and race, differences in LTL across the 3 categories remained significant (F=3.9, P=0.0315). Inactive adults had telomeres that were 170 bp shorter than those meeting the guidelines using jogging/running. This LTL difference was equal to 10.9 yrs of extra biological aging (170/15.6=10.9). Adults performing some jogging/running, but did not meet the guidelines, had LTL that were 105 bp longer than inactive adults. CONCLUSION: The present study indicates that ≥ 75 min/wk of jogging/running accounts for almost 11 yrs less cellular aging compared to being physically inactive

Varicella zoster virus differentially alters morphology and suppresses proinflammatory cytokines in primary human spinal cord and hippocampal astrocytes

Abstract Background Varicella zoster virus (VZV) is a ubiquitous alphaherpesvirus that produces varicella and zoster. VZV can infect multiple cell types in the spinal cord and brain, including astrocytes, producing myelopathy and encephalopathy. While studies of VZV-astrocyte interactions are sparse, a recent report showed that quiescent primary human spinal cord astrocytes (qHA-sps) did not appear activated morphologically during VZV infection. Since astrocytes play a critical role in host defenses during viral infections of the central nervous system, we examined the cytokine responses of qHA-sps and quiescent primary human hippocampal astrocytes (qHA-hps) to VZV infection in vitro, as well as the ability of conditioned supernatant to recruit immune cells. Methods At 3 days post-infection, mock- and VZV-infected qHA-sps and qHA-hps were examined for morphological changes by immunofluorescence antibody assay using antibodies directed against glial fibrillary acidic protein and VZV. Conditioned supernatants were analyzed for proinflammatory cytokines [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-gamma, and tumor necrosis factor-α] using the Meso Scale Discovery multiplex ELISA platform. Finally, the ability of conditioned supernatants to attract peripheral blood mononuclear cells (PBMCs) was determined using a chemotaxis assay. Quiescent primary human perineurial cells (qHPNCs) served as a control for VZV-induced cytokine production and PBMC migration. To confirm that the astrocytes have the ability to increase cytokine secretion, qHA-sps and qHA-hps were treated with IL-1β and examined for morphological changes and IL-6 secretion. Results VZV-infected qHA-sps displayed extensive cellular processes, whereas VZV-infected qHA-hps became swollen and clustered together. Astrocytes had the capacity to secrete IL-6 in response to IL-1β. Compared to mock-infected cells, VZV-infected qHA-sps showed significantly reduced secretion of IL-2, IL-4, IL-6, IL-12p70, and IL-13, while VZV-infected qHA-hps showed significantly reduced IL-8 secretion. In contrast, levels of all 10 cytokines examined were significantly increased in VZV-infected qHPNCs. Consistent with these results, conditioned supernatant from VZV-infected qHPNCs, but not that from VZV-infected qHA-sps and qHA-hps, recruited PBMCs. Conclusions VZV-infected qHA-sps and qHA-hps have distinct morphological alterations and patterns of proinflammatory cytokine suppression that could contribute to ineffective viral clearance in VZV myelopathy and encephalopathy, respectively

Varicella zoster virus productively infects human peripheral blood mononuclear cells to modulate expression of immunoinhibitory proteins and blocking PD-L1 enhances virus-specific CD8+ T cell effector function.

Varicella zoster virus (VZV) is a lymphotropic alpha-herpesvirinae subfamily member that produces varicella on primary infection and causes zoster, vascular disease and vision loss upon reactivation from latency. VZV-infected peripheral blood mononuclear cells (PBMCs) disseminate virus to distal organs to produce clinical disease. To assess immune evasion strategies elicited by VZV that may contribute to dissemination of infection, human PBMCs and VZV-specific CD8+ T cells (V-CD8+) were mock- or VZV-infected and analyzed for immunoinhibitory protein PD-1, PD-L1, PD-L2, CTLA-4, LAG-3 and TIM-3 expression using flow cytometry. All VZV-infected PBMCs (monocytes, NK, NKT, B cells, CD4+ and CD8+ T cells) and V-CD8+ showed significant elevations in PD-L1 expression compared to uninfected cells. VZV induced PD-L2 expression in B cells and V-CD8+. Only VZV-infected CD8+ T cells, NKT cells and V-CD8+ upregulated PD-1 expression, the immunoinhibitory receptor for PD-L1/PD-L2. VZV induced CTLA-4 expression only in V-CD8+ and no significant changes in LAG-3 or TIM-3 expression were observed in V-CD8+ or PBMC T cells. To test whether PD-L1, PD-L2 or CTLA-4 regulates V-CD8+ effector function, autologous PBMCs were VZV-infected and co-cultured with V-CD8+ cells in the presence of blocking antibodies against PD-L1, PD-L2 or CTLA-4; ELISAs revealed significant elevations in IFNγ only upon blocking of PD-L1. Together, these results identified additional immune cells that are permissive to VZV infection (monocytes, B cells and NKT cells); along with a novel mechanism for inhibiting CD8+ T cell effector function through induction of PD-L1 expression