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Bartlett, David Bruce

Overview:

David Bartlett is an Instructor in the Department of Medicine, Division of Medical Oncology. He earned his PhD in Immunology from the University of Birmingham, England where he specialized in the effects of exercise and lifestyles on immune function and systemic inflammation in the elderly. He was awarded a coveted Marie Curie Outgoing Fellowship from the European Union which brought him to Duke under the guidance of William Kraus, MD where he assessed the immunological and physiological responses of exercise training in patients with prediabetes and rheumatoid arthritis. His laboratory studies the effects of exercise and energy balance on immune function and physiology of patient groups including cancer, arthritis and diabetes. His research program is focused on human studies employing a wide range of techniques including human physiological testing such as cardiopulmonary fitness assessment, exercise training to in vitro and ex vivo cellular assays. 

Positions:

Medical Instructor in the Department of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2014

Ph.D. — University of Birmingham

Publications:

Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma.

Multiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow. This microenvironment facilitates crucial interactions between the cancer cells and stromal cell types that permit the tumour to survive and proliferate. There is increasing evidence that the bone marrow mesenchymal stem cell (BMMSC) is stably altered in patients with MM-a phenotype also postulated to exist in patients with monoclonal gammopathy of undetermined significance (MGUS) a benign condition that precedes MM. In this study, we describe a mechanism by which increased expression of peptidyl arginine deiminase 2 (PADI2) by BMMSCs in patients with MGUS and MM directly alters malignant plasma cell phenotype. We identify PADI2 as one of the most highly upregulated transcripts in BMMSCs from both MGUS and MM patients, and that through its enzymatic deimination of histone H3 arginine 26, PADI2 activity directly induces the upregulation of interleukin-6 expression. This leads to the acquisition of resistance to the chemotherapeutic agent, bortezomib, by malignant plasma cells. We therefore describe a novel mechanism by which BMMSC dysfunction in patients with MGUS and MM directly leads to pro-malignancy signalling through the citrullination of histone H3R26.

Authors
McNee, G; Eales, KL; Wei, W; Williams, DS; Barkhuizen, A; Bartlett, DB; Essex, S; Anandram, S; Filer, A; Moss, PAH; Pratt, G; Basu, S; Davies, CC; Tennant, DA
MLA Citation
McNee, G, Eales, KL, Wei, W, Williams, DS, Barkhuizen, A, Bartlett, DB, Essex, S, Anandram, S, Filer, A, Moss, PAH, Pratt, G, Basu, S, Davies, CC, and Tennant, DA. "Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma." Leukemia 31.2 (February 2017): 373-381.
PMID
27400413
Source
epmc
Published In
Leukemia
Volume
31
Issue
2
Publish Date
2017
Start Page
373
End Page
381
DOI
10.1038/leu.2016.187

Lifestyle Interventions to Improve Immunesenescence

Regular participation in exercise and physical activity is associated with many health benefits including improvements in metabolic and cardiorespiratory function. However, as we get older the time and intensity at which we exercise is severely reduced. Physical inactivity now accounts for a considerable proportion of age-related disease and mortality. These diseases are associated with an increased systemic inflammatory milieu and immunesenescence. Regular exercise and physical activity has been suggested to exert anti-inflammatory and anti-immunesenescence effects, potentially delaying the health declines with ageing. No immune cells are impervious to the effects of ageing and exercise appears to modify many immunological functions. Regular exercise has been shown to improve neutrophil microbicidal functions which reduce the risk of infectious disease. Exercise participation is also associated with increased immune cell telomere length, and may be related to improved vaccine responses. The anti-inflammatory effect of regular exercise and negative energy balance is evident by reduced inflammatory immune cell signatures and lower inflammatory cytokine concentrations. In this chapter we will discuss the role of physical activity and energy balance in modifying the immune system. Specifically we discuss what role each plays on limiting the incidence of immunesenescence in older adults.

Authors
Bartlett, DB; Huffman, KM
MLA Citation
Bartlett, DB, and Huffman, KM. "Lifestyle Interventions to Improve Immunesenescence." The Ageing Immune System and Health. Springer, October 18, 2016. (Chapter)
Source
manual
Publish Date
2016
DOI
10.1007/978-3-319-43365-3_10

Habitual physical activity is associated with the maintenance of neutrophil migratory dynamics in healthy older adults.

Dysfunctional neutrophils with advanced age are a hallmark of immunosenescence. Reduced migration and bactericidal activity increase the risk of infection. It remains unclear why neutrophil dysfunction occurs with age. Physical activity and structured exercise have been suggested to improve immune function in the elderly. The aim of this study was to assess a comprehensive range of neutrophil functions and determine their association with habitual physical activity.Physical activity levels were determined in 211 elderly (67±5years) individuals by 7-days of accelerometry wear. Twenty of the most physically active men and women were matched for age and gender to twenty of the least physically active individuals. Groups were compared for neutrophil migration, phagocytosis, oxidative burst, cell surface receptor expression, metabolic health parameters and systemic inflammation. Groups were also compared against ten young participants (23±4years).The most active group completed over twice as many steps/day as the least active group (p<0.001), had lower BMI's (p=0.007) and body fat percentages (p=0.029). Neutrophils migrated towards IL-8 better in the most active group compared to the least active (p<0.05) and was comparable to that of the young (p>0.05). These differences remained after adjusting for BMI, body fat and plasma metabolic markers which were different between groups. Correlations revealed that steps/day, higher adiponectin and lower insulin were positively associated with migratory ability (p<0.05). There was no difference in expression of the chemokine receptors CXCR1 or CXCR2 (p>0.05 for both). CD11b was higher in the most active group compared to the least active (p=0.048). No differences between activity groups or young controls were observed for neutrophil phagocytosis or oxidative burst in response to Escherichia coli (p>0.05). The young group had lower concentrations of IL-6, IL-8, MCP-1, CRP, IL-10 and IL-13 (p<0.05 for all) with no differences between the two older groups.These data suggest that impaired neutrophil migration, but not bactericidal function, in older adults may be, in part, the result of reduced physical activity. A 2-fold difference in physical activity is associated with better preserved neutrophil migratory dynamics in healthy older people. As a consequence increasing habitual physical activity may be beneficial for neutrophil mediated immunity.

Authors
Bartlett, DB; Fox, O; McNulty, CL; Greenwood, HL; Murphy, L; Sapey, E; Goodman, M; Crabtree, N; Thøgersen-Ntoumani, C; Fisher, JP; Wagenmakers, AJM; Lord, JM
MLA Citation
Bartlett, DB, Fox, O, McNulty, CL, Greenwood, HL, Murphy, L, Sapey, E, Goodman, M, Crabtree, N, Thøgersen-Ntoumani, C, Fisher, JP, Wagenmakers, AJM, and Lord, JM. "Habitual physical activity is associated with the maintenance of neutrophil migratory dynamics in healthy older adults." Brain, behavior, and immunity 56 (August 2016): 12-20.
PMID
26928196
Source
epmc
Published In
Brain, Behavior, and Immunity
Volume
56
Publish Date
2016
Start Page
12
End Page
20
DOI
10.1016/j.bbi.2016.02.024

A novel inflammatory biomarker, GlycA, associates with disease activity in rheumatoid arthritis and cardio-metabolic risk in BMI-matched controls.

RA and CVD both have inflammation as part of the underlying biology. Our objective was to explore the relationships of GlycA, a measure of glycosylated acute phase proteins, with inflammation and cardiometabolic risk in RA, and explore whether these relationships were similar to those for persons without RA.Plasma GlycA was determined for 50 individuals with mild-moderate RA disease activity and 39 controls matched for age, gender, and body mass index (BMI). Regression analyses were performed to assess relationships between GlycA and important markers of traditional inflammation and cardio-metabolic health: inflammatory cytokines, disease activity, measures of adiposity and insulin resistance.On average, RA activity was low (DAS-28 = 3.0 ± 1.4). Traditional inflammatory markers, ESR, hsCRP, IL-1β, IL-6, IL-18 and TNF-α were greater in RA versus controls (P < 0.05 for all). GlycA concentrations were significantly elevated in RA versus controls (P = 0.036). In RA, greater GlycA associated with disease activity (DAS-28; RDAS-28 = 0.5) and inflammation (RESR = 0.7, RhsCRP = 0.7, RIL-6 = 0.3: P < 0.05 for all); in BMI-matched controls, these inflammatory associations were absent or weaker (hsCRP), but GlycA was related to IL-18 (RhsCRP = 0.3, RIL-18 = 0.4: P < 0.05). In RA, greater GlycA associated with more total abdominal adiposity and less muscle density (Rabdominal-adiposity = 0.3, Rmuscle-density = -0.3, P < 0.05 for both). In BMI-matched controls, GlycA associated with more cardio-metabolic markers: BMI, waist circumference, adiposity measures and insulin resistance (R = 0.3-0.6, P < 0.05 for all).GlycA provides an integrated measure of inflammation with contributions from traditional inflammatory markers and cardio-metabolic sources, dominated by inflammatory markers in persons with RA and cardio-metabolic factors in those without.

Authors
Bartlett, DB; Connelly, MA; AbouAssi, H; Bateman, LA; Tune, KN; Huebner, JL; Kraus, VB; Winegar, DA; Otvos, JD; Kraus, WE; Huffman, KM
MLA Citation
Bartlett, DB, Connelly, MA, AbouAssi, H, Bateman, LA, Tune, KN, Huebner, JL, Kraus, VB, Winegar, DA, Otvos, JD, Kraus, WE, and Huffman, KM. "A novel inflammatory biomarker, GlycA, associates with disease activity in rheumatoid arthritis and cardio-metabolic risk in BMI-matched controls." Arthritis research & therapy 18 (April 2016): 86-.
Website
http://hdl.handle.net/10161/11953
PMID
27067270
Source
epmc
Published In
Arthritis Research and Therapy
Volume
18
Publish Date
2016
Start Page
86
DOI
10.1186/s13075-016-0982-5

Neutrophil function in young and old caregivers.

The present study examined the effects of caregiving stress and ageing on neutrophil function in young and older individuals.As a model of caregiving, young parents (aged 38.3 ± 4.78) of children with developmental disabilities were recruited and compared to older caregivers (aged 70 ± 6.03), full time carers of a spouse with dementia. Age- and gender-matched controls were also assessed.Participants completed a questionnaire pack assessing health behaviours, psychosocial status and caregiving characteristics, and provided a blood sample for assay of neutrophil function (phagocytosis of Escherichia coli and generation of reactive oxygen species to E. coli).Despite scoring poorly on the majority of psychological and caregiving variables, neutrophil function in caregivers was comparable to that in controls and was unexpectedly higher in older adults when compared to younger adults overall. However, those caregivers who reported higher psychological morbidity (depression, perceived stress, poor sleep quality), and more burdensome caregiving showed some evidence of poorer neutrophil phagocytic function.To our knowledge, this is the first study to examine the effect of caregiving stress on neutrophil function in young and older participants simultaneously. Overall, neutrophil function was preserved in caregivers with neutrophil phagocytosis compromised only in those with the highest levels of distress. This suggests that, in future studies, more attention should be paid to individual differences among caregivers rather than caregiving status per se.What is already known on this subject? Ageing is accompanied by the decrease in innate and adaptive immunity, termed immunosenescence. Caregiving stress has been shown to exert negative effect on immune function in both young and old. What does this study add? The study examined effect of caregiving and ageing simultaneously in four groups of participants. Neutrophil function and stress hormone levels were preserved in the stressed in both age groups. Those with higher psychological morbidity had poorer neutrophil phagocytosis.

Authors
Vitlic, A; Lord, JM; Taylor, AE; Arlt, W; Bartlett, DB; Rossi, A; Arora-Duggal, N; Welham, A; Heald, M; Oliver, C; Carroll, D; Phillips, AC
MLA Citation
Vitlic, A, Lord, JM, Taylor, AE, Arlt, W, Bartlett, DB, Rossi, A, Arora-Duggal, N, Welham, A, Heald, M, Oliver, C, Carroll, D, and Phillips, AC. "Neutrophil function in young and old caregivers." British journal of health psychology 21.1 (February 2016): 173-189.
PMID
26285690
Source
epmc
Published In
British Journal of Health Psychology
Volume
21
Issue
1
Publish Date
2016
Start Page
173
End Page
189
DOI
10.1111/bjhp.12156

Alterations in bone marrow metabolism are an early and consistent feature during the development of MGUS and multiple myeloma.

Authors
Ludwig, C; Williams, DS; Bartlett, DB; Essex, SJ; McNee, G; Allwood, JW; Jewell, E; Barkhuisen, A; Parry, H; Anandram, S; Nicolson, P; Gardener, C; Seymour, F; Basu, S; Dunn, WB; Moss, PAH; Pratt, G; Tennant, DA
MLA Citation
Ludwig, C, Williams, DS, Bartlett, DB, Essex, SJ, McNee, G, Allwood, JW, Jewell, E, Barkhuisen, A, Parry, H, Anandram, S, Nicolson, P, Gardener, C, Seymour, F, Basu, S, Dunn, WB, Moss, PAH, Pratt, G, and Tennant, DA. "Alterations in bone marrow metabolism are an early and consistent feature during the development of MGUS and multiple myeloma." Blood cancer journal 5 (January 2015): e359-. (letter, Letter)
PMID
26473531
Source
epmc
Published In
Blood Cancer Journal
Volume
5
Publish Date
2015
Start Page
e359
DOI
10.1038/bcj.2015.85

Inflammation, telomere length, and grip strength: a 10-year longitudinal study.

Telomere attrition has been associated with age-related diseases, although causality is unclear and controversial; low-grade systemic inflammation (inflammaging) has also been implicated in age-related pathogenesis. Unpicking the relationship between aging, telomere length (TL), and inflammaging is hence essential to the understanding of aging and management of age-related diseases. This longitudinal study explored whether telomere attrition is a cause or consequence of aging and whether inflammaging explains some of the associations between TL and one marker of aging, grip strength. We studied 253 Hertfordshire Ageing Study participants at baseline and 10-year follow-up (mean age at baseline 67.1 years). Participants completed a health questionnaire and had blood samples collected for immune-endocrine and telomere analysis at both time points. Physical aging was characterized at follow-up using grip strength. Faster telomere attrition was associated with lower grip strength at follow-up (β = 0.98, p = 0.035). This association was completely attenuated when adjusted for inflammaging burden (p = 0.86) over the same period. Similarly, greater inflammaging burden was associated with lower grip strength at follow-up (e.g., interleukin [IL]-1β: β = -2.18, p = 0.001). However, these associations were maintained when adjusted for telomere attrition (IL-1β, p = 0.006). We present evidence that inflammaging may be driving telomere attrition and in part explains the associations that have previously been reported between TL and grip strength. Thus, biomarkers of physical aging, such as inflammaging, may require greater exploration. Further work is now indicated.

Authors
Baylis, D; Ntani, G; Edwards, MH; Syddall, HE; Bartlett, DB; Dennison, EM; Martin-Ruiz, C; von Zglinicki, T; Kuh, D; Lord, JM; Aihie Sayer, A; Cooper, C
MLA Citation
Baylis, D, Ntani, G, Edwards, MH, Syddall, HE, Bartlett, DB, Dennison, EM, Martin-Ruiz, C, von Zglinicki, T, Kuh, D, Lord, JM, Aihie Sayer, A, and Cooper, C. "Inflammation, telomere length, and grip strength: a 10-year longitudinal study." Calcified tissue international 95.1 (July 2014): 54-63.
PMID
24858709
Source
epmc
Published In
Calcified Tissue International
Volume
95
Issue
1
Publish Date
2014
Start Page
54
End Page
63
DOI
10.1007/s00223-014-9862-7

Supporting healthy ageing: Training multi-disciplinary healthcare students

Authors
Shneerson, C; Bartlett, D; Lord, J; Gale, N
MLA Citation
Shneerson, C, Bartlett, D, Lord, J, and Gale, N. "Supporting healthy ageing: Training multi-disciplinary healthcare students." European Journal of Integrative Medicine 6.1 (February 2014): 104-111.
Source
crossref
Published In
European Journal of Integrative Medicine
Volume
6
Issue
1
Publish Date
2014
Start Page
104
End Page
111
DOI
10.1016/j.eujim.2013.12.021

Immune-endocrine biomarkers as predictors of frailty and mortality: a 10-year longitudinal study in community-dwelling older people.

Frailty is a multidimensional geriatric syndrome characterised by a state of increased vulnerability to disease. Its causes are unclear, limiting opportunities for intervention. Age-related changes to the immune-endocrine axis are implicated. This study investigated the associations between the immune-endocrine axis and frailty as well as mortality 10 years later among men and women aged 65 to 70 years. We studied 254 participants of the Hertfordshire Ageing Study at baseline and 10-year follow-up. At baseline, they completed a health questionnaire and had collection of blood samples for immune-endocrine analysis. At follow-up, Fried frailty was characterised and mortality ascertained. Higher baseline levels of differential white cell counts (WCC), lower levels of dehydroepiandosterone sulphate (DHEAS) and higher cortisol:DHEAS ratio were all significantly associated with increased odds of frailty at 10-year follow-up. Baseline WCC and cortisol:DHEAS clearly discriminated between individuals who went on to be frail at follow-up. We present the first evidence that immune-endocrine biomarkers are associated with the likelihood of frailty as well as mortality over a 10-year period. This augments our understanding of the aetiology of frailty, and suggests that a screening programme at ages 60-70 years could help to identify individuals who are at high risk of becoming frail and who would benefit from early, targeted intervention, for example with DHEA supplementation or anti-inflammatory strategies. Progress towards the prevention of frailty would bring major health and socio-economic benefits at the individual and the population level.

Authors
Baylis, D; Bartlett, DB; Syddall, HE; Ntani, G; Gale, CR; Cooper, C; Lord, JM; Sayer, AA
MLA Citation
Baylis, D, Bartlett, DB, Syddall, HE, Ntani, G, Gale, CR, Cooper, C, Lord, JM, and Sayer, AA. "Immune-endocrine biomarkers as predictors of frailty and mortality: a 10-year longitudinal study in community-dwelling older people." Age (Dordrecht, Netherlands) 35.3 (June 2013): 963-971.
PMID
22388931
Source
epmc
Published In
AGE
Volume
35
Issue
3
Publish Date
2013
Start Page
963
End Page
971
DOI
10.1007/s11357-012-9396-8

Meeting report: British Society for Research on Ageing (BSRA) annual scientific meeting 2012, Aston University, Birmingham, 3rd to 4th July 2012.

The focus of the British Society for Research on Ageing (BSRA) annual scientific meeting 2012 was aging mechanisms and mitigants. The themes covered included epigenetics, stem cells and regeneration, aging pathways and molecules, the aging bladder and bowel, as well as updates from the New Dynamics of Ageing (NDA) programme. The topics incorporated new directions for staple aging research in caloric restriction (CR), inflammation, immunesenescence, neurodegeneration, homeostasis and stress resistance, as well as newer research areas such as bioengineering of tissues, including the internal anal sphincter and thymus.

Authors
Greenwood, H; Bartlett, DB
MLA Citation
Greenwood, H, and Bartlett, DB. "Meeting report: British Society for Research on Ageing (BSRA) annual scientific meeting 2012, Aston University, Birmingham, 3rd to 4th July 2012." Longevity & healthspan 2.1 (January 2013): 6-.
PMID
24472617
Source
epmc
Published In
Longevity and Healthspan
Volume
2
Issue
1
Publish Date
2013
Start Page
6
DOI
10.1186/2046-2395-2-6

Understanding how we age: insights into inflammaging.

Inflammaging is characterized by the upregulation of the inflammatory response that occurs with advancing age; its roots are strongly embedded in evolutionary theory.Inflammaging is believed to be a consequence of a remodelling of the innate and acquired immune system, resulting in chronic inflammatory cytokine production.Complex interrelated genetic, environmental and age-related factors determine an individual's vulnerability or resilience to inflammaging. These factors include polymorphisms to the promoter regions of cytokines, cytokine receptors and antagonists, age-related decreases in autophagy and increased adiposity. Anti-inflammaging describes the upregulation of the hypothalamic-pituitary axis in response to inflammaging, leading to higher levels of cortisol, which in turn may be detrimental, contributing to less successful ageing and frailty. This may be countered by the adrenal steroid dehydroepiandrosterone, which itself declines with age, leaving certain individuals more vulnerable. Inflammaging and anti-inflammaging have both been linked with a number of age-related outcomes, including chronic morbidity, functional decline and mortality. This important area of research offers unique insights into the ageing process and the potential for screening and targeted interventions.

Authors
Baylis, D; Bartlett, DB; Patel, HP; Roberts, HC
MLA Citation
Baylis, D, Bartlett, DB, Patel, HP, and Roberts, HC. "Understanding how we age: insights into inflammaging." Longevity & healthspan 2.1 (January 2013): 8-.
PMID
24472098
Source
epmc
Published In
Longevity and Healthspan
Volume
2
Issue
1
Publish Date
2013
Start Page
8
DOI
10.1186/2046-2395-2-8

The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection.

Aging is accompanied by the development of low-grade systemic inflammation, termed 'inflammaging', characterized by raised serum C-reactive protein (CRP) and pro-inflammatory cytokines. Importantly, inflammaging is implicated in the pathogenesis of several of the major age-related diseases including cardiovascular disease, type 2 diabetes, and dementia and is associated with increased mortality. The incidence of infection with the persistent herpes virus cytomegalovirus (CMV) also increases with age. Cross-sectional studies have proposed CMV infection as a significant driver of inflammaging, but a definitive case for CMV as a causative agent in inflammaging has not yet been made. We studied longitudinally 249 subjects (153 men, 96 women) who participated in the Hertfordshire Ageing Study at baseline (1993/5, mean age 67·5 years) and at 10 year follow-up. At both times, anthropometric measurements were made and subjects provided blood samples for analysis of inflammatory status and CMV seropositivity. In the cohort as a whole, serum CRP (P < 0·02) and pro-inflammatory cytokines TNFα (P < 0·001) and IL-6 (P < 0·001) were increased between baseline and follow-up sampling whereas levels of the anti-inflammatory cytokine IL-10 were decreased (P < 0·001). These changes to cytokine status over time occurred equally in the 60% of subjects who were seropositive for CMV at baseline and follow-up, the 8% who were CMV negative at baseline but who became CMV positive by the 10 year follow-up, and also in the 32% who were CMV seronegative throughout. We conclude that CMV infection is not a primary causative factor in the age-related increase in systemic inflammation.

Authors
Bartlett, DB; Firth, CM; Phillips, AC; Moss, P; Baylis, D; Syddall, H; Sayer, AA; Cooper, C; Lord, JM
MLA Citation
Bartlett, DB, Firth, CM, Phillips, AC, Moss, P, Baylis, D, Syddall, H, Sayer, AA, Cooper, C, and Lord, JM. "The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection." Aging cell 11.5 (October 2012): 912-915.
PMID
22708923
Source
epmc
Published In
Aging Cell
Volume
11
Issue
5
Publish Date
2012
Start Page
912
End Page
915
DOI
10.1111/j.1474-9726.2012.00849.x

Latent CMV And EBV Infections And The Mobilization Of Viral-specific And Senescent T-cells With Exercise

Authors
Simpson, RJ; Spielmann, G; Bigley, AB; Rector, JL; Bartlett, DB; Morrison, MR
MLA Citation
Simpson, RJ, Spielmann, G, Bigley, AB, Rector, JL, Bartlett, DB, and Morrison, MR. "Latent CMV And EBV Infections And The Mobilization Of Viral-specific And Senescent T-cells With Exercise." JOURNAL OF GENERAL INTERNAL MEDICINE 27 (July 2012): 487-487.
Source
wos-lite
Published In
Journal of General Internal Medicine
Volume
27
Publish Date
2012
Start Page
487
End Page
487

Latent CMV And EBV Infections And The Mobilization Of Viral-specific And Senescent T-cells With Exercise

Authors
Simpson, RJ; Spielmann, G; Bigley, AB; Rector, JL; Bartlett, DB; Morrison, MR
MLA Citation
Simpson, RJ, Spielmann, G, Bigley, AB, Rector, JL, Bartlett, DB, and Morrison, MR. "Latent CMV And EBV Infections And The Mobilization Of Viral-specific And Senescent T-cells With Exercise." MEDICINE AND SCIENCE IN SPORTS AND EXERCISE 43.5 (May 2011): 487-487.
Source
wos-lite
Published In
Medicine and Science in Sports and Exercise
Volume
43
Issue
5
Publish Date
2011
Start Page
487
End Page
487

Senescent phenotypes and telomere lengths of peripheral blood T-cells mobilized by acute exercise in humans.

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.

Authors
Simpson, RJ; Cosgrove, C; Chee, MM; McFarlin, BK; Bartlett, DB; Spielmann, G; O'Connor, DP; Pircher, H; Shiels, PG
MLA Citation
Simpson, RJ, Cosgrove, C, Chee, MM, McFarlin, BK, Bartlett, DB, Spielmann, G, O'Connor, DP, Pircher, H, and Shiels, PG. "Senescent phenotypes and telomere lengths of peripheral blood T-cells mobilized by acute exercise in humans." Exercise immunology review 16 (January 2010): 40-55.
PMID
20839490
Source
epmc
Published In
Exercise immunology review
Volume
16
Publish Date
2010
Start Page
40
End Page
55
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