Dr David Bartlett


Lecturer of Exercise Immunology

About

Areas of specialism

Cellular and Molecular Immunology; Immunometabolism; Inflammation; Clinical Exercise Physiology; Ageing and Chronic Diseases

Affiliations and memberships

American College of Sports Medicine
Member
American Society of Hematology
Clinical Fellow
Gerontological Society of America
Member
International Society of Exercise and Immunology
Member

News

Research

Research interests

Research projects

Indicators of esteem

  • Because of my work investigating the effects of high-intensity interval training in adults with chronic diseases, I was invited as a support staff member on the 2018 Physical Activity Guidelines for Americans. From this, we published a Special Communication in Medicine & Science in Sports & Exercise titled "High-Intensity Interval Training for Cardiometabolic Disease Prevention."

    Supervision

    Postgraduate research supervision

    Teaching

    Publications

    Highlights

    I have published >40 papers on the effects of exercise on the immune system in various diseases. Below is a highlight of my work in exercise oncology and exercise rheumatology. You will find links to all of my publications below these highlights. 

    Exercise Oncology

    1. Andrea Sitlinger, Michael A Deal, Erwin Garcia, Margery A Connelly, Dana K Thompson, T Stewart, Grace MacDonald, Erik D Hanson, Megan Neely, Ben Neely, Ashley Artese, J. Brice Weinberg, Danielle M Brander, David B. Bartlett, David B. Bartlett (2022). Associations of clinical and circulating metabolic biomarkers with low physical fitness and function in adults with chronic lymphocytic leukemia, In: Frontiers in oncology12933619 Frontiers Media S.A
    2. Erik D Hanson, Mohamdod S Alzer, JR Carver, Cameron K Stopforth, Alexander R Lucas, Young E Whang, Matthew I Milowsky, David B. Bartlett, M Harrison, Rhonda L Bitting, Allison M Deal, Lee Stoner, A C Hackney, Claudio L Battaglini (2022)Feasibility of home-based exercise training in men with metastatic castration-resistant prostate cancer, In: Prostate cancer and prostatic diseases. DOI: 10.1038/s41391-022-00523-8
    3. M Harrison, Paul Davis, Michel G Khouri, David B. Bartlett, Rajan T Gupta, A Armstrong, Megan A McNamara, Tian-Ping Zhang, M Anand, Kelly Onyenwoke, Sara Edwardson, Danielle Craig, Meghan Michalski, Yuan Wu, Taofik Oyekunle, Brian Coyne, Aubrie Coburn, Lee W Jones, DJ George (2022)A randomized controlled trial comparing changes in fitness with or without supervised exercise in patients initiated on enzalutamide and androgen deprivation therapy for non-metastatic castration-sensitive prostate cancer (EXTEND), In: Prostate cancer and prostatic diseases. DOI: 10.1038/s41391-022-00519-4
    4. Grace MacDonald, Andrea Sitlinger, Michael A Deal, Erik D Hanson, Stephanie Ferraro, Carl F Pieper, J. Brice Weinberg, Danielle M Brander, David B. Bartlett (2021)A pilot study of high-intensity interval training in older adults with treatment naïve chronic lymphocytic leukemia, In: Scientific reports11(1)pp. 23137-23137 DOI: 10.1038/s41598-021-02352-6
    5. David B. Bartlett, Erik D Hanson, Jordan T Lee, Chad W Wagoner, Elizabeth P Harrell, Stephanie A Sullivan, Lauren C Bates, Mohamdod S Alzer, Dean J Amatuli, Allison M Deal, Brian C Jensen, Grace MacDonald, Michael A Deal, Hyman B Muss, Kirsten A Nyrop, Claudio L Battaglini (2021)The Effects of 16 Weeks of Exercise Training on Neutrophil Functions in Breast Cancer Survivors, In: Frontiers in immunology12pp. 733101-733101. DOI: 10.3389/fimmu.2021.733101
    6. Erik D Hanson, Lauren C Bates, Elizabeth P Harrell, David B. Bartlett, Jordan T Lee, Chad W Wagoner, Mohamdod S Alzer, Dean J Amatuli, Brian C Jensen, Allison M Deal, Hyman B Muss, Kirsten A Nyrop, Claudio L Battaglini (2021)Exercise training partially rescues impaired mucosal associated invariant t-cell mobilization in breast cancer survivors compared to healthy older women, In: Experimental gerontology152111454 Elsevier Inc. DOI: 10.1016/j.exger.2021.111454
    7. Nasim Khosravi, Erik D Hanson, Vahid Farajivafa, William S Evans, Jordan T Lee, Eli Danson, Chad W Wagoner, Elizabeth P Harrell, Stephanie A Sullivan, Kirsten A Nyrop, Hyman B Muss, David B. Bartlett, Brian C Jensen, Shahpar Haghighat, Mahdieh Molanouri Shamsi, Claudio L Battaglini (2021)Exercise-induced modulation of monocytes in breast cancer survivors, In: Brain, behavior, & immunity. Health14pp. 100216-100216 Elsevier Inc. DOI: 10.1016/j.bbih.2021.100216
    8. Amanda R Schwartz, David B. Bartlett, J Johnson, Gloria Broadwater, Meghan Channell, Kimberly C Nolte, Patricia A Wilkes, Kim M Huffman, Angeles Alvarez Secord (2021)A Pilot Study of Home-Based Exercise and Personalized Nutrition Counseling Intervention in Endometrial Cancer Survivors, In: Frontiers in oncology11pp. 669961-669961 Frontiers Media S.A DOI: 10.3389/fonc.2021.669961
    9. Andrea Sitlinger, Michael A Deal, Erwin Garcia, Dana K Thompson, T Stewart, Grace MacDonald, Nicolas Devos, David Corcoran, Janet S Staats, Jennifer Enzor, Kent J Weinhold, Danielle M Brander, J. Brice Weinberg, David B. Bartlett (2021)Physiological Fitness and the Pathophysiology of Chronic Lymphocytic Leukemia (CLL), In: Cells (Basel, Switzerland)10(5) MDPI DOI: 10.3390/cells10051165
    10. Erik D Hanson, Cameron K Stopforth, Mohamdod S Alzer, JR Carver, Alexander R Lucas, Young E Whang, Matthew I Milowsky, David B. Bartlett, M Harrison, A Hayes, Rhonda L Bitting, Allison M Deal, A C Hackney, Claudio L Battaglini (2021)Body composition, physical function and quality of life in healthy men and across different stages of prostate cancer, In: Prostate cancer and prostatic diseases24(3)pp. 725-732 DOI: 10.1038/s41391-020-00317-w
    11. David B. Bartlett, Gloria Broadwater, Heidi K White, Rebecca Shelby, Leah L Zullig, J Robertson, Ravindran Kanesvaran, H Cohen, Gretchen Kimmick (2020)Factors associated with falls in older women with breast cancer: the use of a brief geriatric screening tool in clinic, In: Breast cancer research and treatment184(2)pp. 445-457 Springer DOI: 10.1007/s10549-020-05862-5
    12. Erik D Hanson, Samy Sakkal, Shadney Que, Eunhan Cho, Guillaume Spielmann, Elif Kadife, John A Violet, Claudio L Battaglini, Lee Stoner, David B. Bartlett, Glenn K McConell, A Hayes (2020)Natural killer cell mobilization and egress following acute exercise in men with prostate cancer, In: Experimental physiology105(9)pp. 1524-1539 Wiley DOI: 10.1113/EP088627
    13. Andrea Sitlinger, Danielle M Brander, David B. Bartlett (2020)Impact of exercise on the immune system and outcomes in hematologic malignancies, In: Blood advances4(8)pp. 1801-1811 Ash publications DOI: 10.1182/bloodadvances.2019001317

    Exercise & Rheumatology

    1. Brian J Andonian, Alec Koss, Timothy R Koves, E Hauser, Monica J Hubal, David M Pober, J Lord, Nancie J MacIver, E William St Clair, Deborah M Muoio, William E Kraus, David B. Bartlett, Kim M Huffman (2022)Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness, In: Scientific Reports. DOI: 10.1038/s41598-022-11458-4

    2. Brian J Andonian, Andrew Johannemann, Monica J Hubal, David M Pober, Alec Koss, William E Kraus, David B. Bartlett, Kim M Huffman (2021)Altered skeletal muscle metabolic pathways, age, systemic inflammation, and low cardiorespiratory fitness associate with improvements in disease activity following high-intensity interval training in persons with rheumatoid arthritis, In: Arthritis research & therapy 23(1)pp. 1-187 BioMed Central DOI: 10.1186/s13075-021-02570-3

    3. Brian J Andonian, David B. Bartlett, Janet L Huebner, Leslie H Willis, Andrew Hoselton, Virginia B Kraus, William E Kraus, Kim M Huffman (2018) Effect of high-intensity interval training on muscle remodelling in rheumatoid arthritis compared to prediabetes, In: Arthritis research & therapy 20(1)pp. 283-283 BioMed Central DOI: 10.1186/s13075-018-1786-6

    4. David B. Bartlett, Leslie H Willis, Cris A Slentz, Andrew Hoselton, Leslie Kelly, Janet L Huebner, Virginia B Kraus, Jennifer Moss, Michael J Muehlbauer, Guillaume Spielmann, William E Kraus, J Lord, Kim M Huffman (2018)Ten weeks of high-intensity interval walk training is associated with reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis: a pilot study, In: Arthritis research & therapy20(1)pp. 127-127 BioMed Central DOI: 10.1186/s13075-018-1624-x

    5. David B. Bartlett, Margery A Connelly, Hiba AbouAssi, Lori A Bateman, K Noelle Tune, Janet L Huebner, Virginia B Kraus, Deborah A Winegar, James D Otvos, William E Kraus, Kim M Huffman (2016)A novel inflammatory biomarker, GlycA, associates with disease activity in rheumatoid arthritis and cardio-metabolic risk in BMI-matched controls, In: Arthritis research & therapy18(1)pp. 86-86 BMC DOI: 10.1186/s13075-016-0982-5
    Andrea Sitlinger, Michael A Deal, Erwin Garcia, Margery A Connelly, Dana K Thompson, T Stewart, Grace MacDonald, Erik D Hanson, Megan Neely, Ben Neely, Ashley Artese, J. Brice Weinberg, Danielle M Brander, David B. Bartlett, David B. Bartlett, DAVID BARTLETT (2022)Associations of clinical and circulating metabolic biomarkers with low physical fitness and function in adults with chronic lymphocytic leukemia, In: Frontiers in oncology12933619 Frontiers Media S.A

    Many patients with chronic lymphocytic leukemia (CLL) experience physical dysfunction and low overall fitness. It remains unknown what factors drive CLL physical dysfunction. We assessed physical function and metabolic lipoprotein panels in 106 patients with CLL. In univariate analyses of clinical factors, a longer time since diagnosis was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 3.56, 95% CI: 1.37–9.22; p = 0.002) and physical performance (SPPB: OR = 2.03, 95% CI: 1.20–3.44; p = 0.004). Having received treatment was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 1.57, 95% CI: 1.02–2.40; p = 0.036), SPPB (OR = 1.85, 95% CI: 1.13–3.03; p = 0.011) and grip strength (OR = 1.67, 95% CI: 1.10–2.55; p = 0.015). We found that several small HDL particle parameters, higher levels of citrate (OR = 2.01, 95% CI: 1.22–3.31; p = 0.030), and lower levels of hemoglobin (OR = 0.50, 95% CI: 0.31–0.82; p = 0.030) were associated with a higher likelihood of dysfunctional aerobic fitness. Multivariable least absolute shrinkage and selection operator (LASSO)-penalized regression analyses using variable importance measures (VIM) showed that 7.8-nm HDL particles (VIM = 1.000) and total HDL particle levels (VIM = 1.000) were more informative than clinical measures for the odds of dysfunctional aerobic fitness and 6-min walk functional fitness, respectively, while 10.3-nm HDL particles (VIM = 0.383) were more informative for grip strength. Time since diagnosis (VIM = 0.680) and having received treatment (VIM = 0.490) were more informative than lipoprotein measures for the odds of having dysfunctional SPPB. Taken together, we establish significant relationships between clinical and metabolic factors and physical characteristics that might prompt early use of ancillary support services.

    Meagan V. Lew, Yi Ren, Yen P. Lowder, Sharareh Siamakpour-Reihani, Sendhilnathan Ramalingam, Kristi M. Romero, J Thompson, Lauren M. Bohannon, Jackie McIntyre, Helen Tang, Jolien Van Opstal, E Johnson, H Cohen, DAVID BARTLETT, Amy M. Pastva, Miriam Morey, K Hall, Patrick Smith, Katherine B. Peters, Tamara J. Somers, Sarah Kelleher, Sophia K. Smith, Paul E. Wischmeyer, Pao-Hwa Lin, William A. Wood, Glynnis Thorpe, Kerry Minor, Kristi Wiggins, Therese Hennig, Tanya Helms, Renee Welch, B Matthews, JoAnn Liu, Jill Burleson, Thomas Aberant, Ashley K. Engemann, Bethany Henshall, Maurisa Darby, Christina Proch, Michelle Dellascio, Alyssa Pittman, Jacob Suminguit, Taewoong Choi, Cristina Gasparetto, Gwynn D. Long, Richard D. Lopez, Stefanie Sarantopoulos, Mitchell E. Horwitz, Nelson J. Chao, Anthony D. Sung (2022)Geriatric Assessment Reveals Actionable Impairments in Hematopoietic Stem Cell Transplantation Candidates Age 18 to 80 Years, In: Transplantation and cellular therapy28(8)pp. 498.E1-498.E9 Elsevier Inc

    •Geriatric assessment can identify impairments in hematopoietic cell transplantation (HCT) candidates.•Impairments can be found in older (>60 years) as well as younger (18 to 59 years) HCT candidates.•Identifying impairments can facilitate referral and resolution of impairments.•Geriatric assessment may be useful in HCT candidates of all ages. Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for both malignant and nonmalignant hematologic diseases; however, reported rates of treatment-related mortality approach 30%. Outcomes are worse in patients who begin HCT with functional impairments. To detect such impairments, a geriatric assessment (GA) is recommended in adults age ≥65 years. Younger HCT candidates also may be impaired because of chemotherapy regimens pre-HCT. Therefore, we hypothesized that GA can be beneficial for adult patients of all ages and subsequently created a clinical pretransplantation optimization program to assess all HCT candidates using a modified GA. One-hundred fifty-seven patients were evaluated in 4 functional domains— physical, cognitive, nutritional, and psychological—at 2 time points prior to HCT—new patient evaluation (NPE) and sign-off (SO)—between October 2017 and January 2020. At NPE, 80.9% of the patients had at least 1 domain with a functional impairment, and physical (P = .006), cognitive (P = .04), and psychological (P = .04) impairments were associated with an increased likelihood of not proceeding to HCT. In addition, patients age 18 to 39 years were more likely than older patients to have a physical function impairment (P = .001). Between NPE and SO, 51.9% of the patients had resolution of 1 or more impairments, and nutritional impairment at SO was predictive of worse overall survival (P = .01). Our study shows that GA can identify functional impairments in patients of all ages. Early identification of impairments could facilitate referrals to supportive care and resolution of impairments prior to HCT, suggesting that GA could be recommended for HCT candidates of all ages.

    Grace MacDonald, Andrea Sitlinger, Michael A Deal, Erik D Hanson, Stephanie Ferraro, Carl F Pieper, J. Brice Weinberg, Danielle M Brander, DAVID BARTLETT (2021)A pilot study of high-intensity interval training in older adults with treatment naïve chronic lymphocytic leukemia, In: Scientific reports11(1)pp. 23137-23137

    AbstractChronic lymphocytic leukemia (CLL) is the most common leukemia in the USA, affecting predominantly older adults. CLL is characterized by low physical fitness, reduced immunity, and increased risk of secondary malignancies and infections. One approach to improving CLL patients’ physical fitness and immune functions may be participation in a structured exercise program. The aims of this pilot study were to examine physical and immunological changes, and feasibility of a 12-week high-intensity interval training (HIIT) combined with muscle endurance-based resistance training on older adults with treatment naïve CLL. We enrolled eighteen participants with CLL aged 64.9 ± 9.1 years and assigned them to groups depending on distance lived from our fitness center. Ten participants (4 M/6F) completed HIIT and six participants (4 M/2F) completed a non-exercising control group (Controls). HIIT consisted of three 30-min treadmill sessions/week plus two concurrent 30-min strength training sessions/week. Physical and immunological outcomes included aerobic capacity, muscle strength and endurance, and natural killer (NK) cell recognition and killing of tumor cells. We confirmed feasibility if > 70% of HIIT participants completed > 75% of prescribed sessions and prescribed minutes, and if > 80% of high-intensity intervals were at a heart rate corresponding to at least 80% of peak aerobic capacity (VO2peak). Results are presented as Hedge’s G effect sizes (g), with 0.2, 0.5 and 0.8 representing small, medium and large effects, respectively. Following HIIT, leg strength (g = 2.52), chest strength (g = 1.15) and seated row strength (g = 3.07) were 35.4%, 56.1% and 39.5% higher than Controls, respectively, while aerobic capacity was 3.8% lower (g = 0.49) than Controls. Similarly, following HIIT, in vitro NK-cell cytolytic activity against the K562 cell line (g = 1.43), OSU-CLL cell line (g = 0.95), and autologous B-cells (g = 1.30) were 20.3%, 3.0% and 14.6% higher than Controls, respectively. Feasibility was achieved, with HIIT completing 5.0 ± 0.2 sessions/week and 99 ± 3.6% of the prescribed minutes/week at heart rates corresponding to 89 ± 2.8% of VO2peak. We demonstrate that 12-weeks of supervised HIIT combined with muscle endurance-based resistance training is feasible, and that high adherence and compliance are associated with large effects on muscle strength and immune function in older adults with treatment naïve CLL.Trial registration: NCT04950452.

    DAVID BARTLETT, Erik D Hanson, Jordan T Lee, Chad W Wagoner, Elizabeth P Harrell, Stephanie A Sullivan, Lauren C Bates, Mohamdod S Alzer, Dean J Amatuli, Allison M Deal, Brian C Jensen, Grace MacDonald, Michael A Deal, Hyman B Muss, Kirsten A Nyrop, Claudio L Battaglini (2021)The Effects of 16 Weeks of Exercise Training on Neutrophil Functions in Breast Cancer Survivors, In: Frontiers in immunology12pp. 733101-733101

    Following therapy, breast cancer survivors (BCS) have an increased risk of infections because of age and cancer dysregulation of inflammation and neutrophil functions. Neutrophil functions may be improved by exercise training, although limited data exist on exercise and neutrophil functions in BCS.Sixteen BCS [mean age: 56 (SD 11) years old] completed 16 weeks of community-based exercise training and a 45-minute acute bout of cycling before (Base) and after (Final) the exercise training program. Exercise training consisted of 3 x 40 – 60 minute mixed mode aerobic exercises, comprising 10 – 30 minutes aerobic and 30 minutes resistance training. At Base and Final, we took BCS blood samples before (PRE), immediately after (POST), and 1 hour after (1Hr) acute exercise to determine neutrophil counts, phenotype, bacterial killing, IL-6, and IL-8 levels. Eleven healthy, age- and physical activity levels-matched women (Control) completed the acute bout of exercise once as a healthy response reference. Resting Responses. BCS and Controls had similar Base PRE absolute neutrophil counts [mean (SD): 3.3 (1.9) v 3.1 (1.2) x 109/L, p=0.801], but BCS had lower bacterial phagocytosis [3991 (1233) v 4881 (417) MFI, p=0.035] and higher oxidative killing [6254 (1434) v 4709 (1220) MFI, p=0.005], lower CD16 [4159 (1785) v 7018 (1240) MFI, p

    Lauren C Bates, Erik D Hanson, Michael M Levitt, Bryan Richie, Elise Erickson, DAVID BARTLETT, Melody D Phillips (2021)Mucosal-Associated Invariant T Cell Response to Acute Exercise and Exercise Training in Older Obese Women, In: Sports (Basel)9(10) MDPI

    (1) Background: Obesity is a major global public health concern as it is associated with many of the leading causes of preventable deaths. Exercise reduces obesity-induced inflammation; however, it is unknown how exercise training may impact mucosal associated invariant T (MAIT) cells in overweight/obese (OW) post-menopausal women. Therefore, the purpose of this study was to investigate (i) circulating MAIT-cells at rest in OW vs. Lean women, (ii) the response of MAIT-cells to a single bout of combined aerobic and resistance exercise, and (iii) the effects of 12 weeks of exercise training (EX) or educational program (ED) on the MAIT-cell response in OW. (2) Methods: OW completed an acute exercise session or sitting control, underwent 12 weeks of exercise training or received educational materials, and then repeated the exercise session/sitting control. Lean post-menopausal women provided a baseline comparison. (3) Results: OW had lower circulating MAIT-cells at rest than Lean prior to exercise training; however, after training EX displayed improved MAIT-cell frequency. Additionally, prior to training EX did not exhibit MAIT-cell mobilization/egress, however, both improved after training. (4) Conclusions: Reduced MAIT-cell frequency and ability to mobilize/egress were potentially partially rescued in EX after 12 weeks of exercise training; however, further research is needed to elucidate age or obesity-induced attenuations in MAIT-cells.

    Nasim Khosravi, Erik D Hanson, Vahid Farajivafa, William S Evans, Jordan T Lee, Eli Danson, Chad W Wagoner, Elizabeth P Harrell, Stephanie A Sullivan, Kirsten A Nyrop, Hyman B Muss, DAVID BARTLETT, Brian C Jensen, Shahpar Haghighat, Mahdieh Molanouri Shamsi, Claudio L Battaglini (2021)Exercise-induced modulation of monocytes in breast cancer survivors, In: Brain, behavior, & immunity. Health14pp. 100216-100216 Elsevier Inc

    Exercise training reduces inflammation in breast cancer survivors; however, the mechanism is not fully understood. The effects of acute and chronic exercise on monocyte toll-like receptor (TLR2 and 4) expression and intracellular cytokine production were examined in sedentary breast cancer survivors. Eleven women with stage I, II, or III breast cancer within one year of treatment completion performed an acute, intermittent aerobic exercise trial. Blood samples were obtained before, immediately, and 1 h after a 45-min acute exercise trial that was performed before and after 16 weeks of combined aerobic and resistance. LPS-stimulated intracellular IL-1ß, TNF, and IL-6 production, and TLR2 and TLR4 expression were evaluated in CD14+CD16- and CD14+CD16+ monocytes using flow cytometry. Exercise training decreased IL-1ß+CD14+CD16- proportion (24.6%, p=0.016), IL-1ß+CD14+CD16- mean fluorescence intensity (MFI) (−9989, p=0.014), IL-1ß+CD14+CD16+ MFI (−11101, p=0.02), and IL-6+CD14+CD16- proportion (16.9%, P=0.04). TLR2 and TLR4 expression did not change following exercise training but decreased 1 h after acute exercise in CD14+CD16- (−63, p=0.002) and CD14+CD16+ (−18, p=0.006) monocytes, respectively. Immediately after the acute exercise, both monocyte subgroup cell concentration increased, with CD14+CD16+ concentrations being decreased at 1 h post without changes in intracellular cytokine production. Exercise training reduced monocyte intracellular pro-inflammatory cytokine production, especially IL-1ß, although these markers did not change acutely. While acute exercise downregulated the expression of TLR2 and TLR4 on monocytes, this was not sustained over the course of training. These results suggest that the anti-inflammatory effect of combined aerobic and resistance exercise training in breast cancer survivors may be, in part, due to reducing resting monocyte pro-inflammatory cytokine production. •Acute exercise increased monocyte concentrations at 0 h after exercise, with a decrease in CD14+CD16+ monocytes only at 1 h.•Exercise training decreased IL-1β and IL-6 proportions while acute exercise reduced the TLR2 and TLR4 expression.•Anti-inflammatory effect of exercise may be partly explained by reduced pro-inflammatory cytokine production by monocytes.

    Amanda R Schwartz, DAVID BARTLETT, J Johnson, Gloria Broadwater, Meghan Channell, Kimberly C Nolte, Patricia A Wilkes, Kim M Huffman, Angeles Alvarez Secord (2021)A Pilot Study of Home-Based Exercise and Personalized Nutrition Counseling Intervention in Endometrial Cancer Survivors, In: Frontiers in oncology11pp. 669961-669961 Frontiers Media S.A
    DAVID BARTLETT, Cris A Slentz, Leslie H Willis, Andrew Hoselton, Janet L Huebner, Virginia B Kraus, Jennifer Moss, Michael J Muehlbauer, Guillaume Spielmann, Deborah M Muoio, Timothy R Koves, Helena Wu, Kim M Huffman, J Lord, William E Kraus (2020)Rejuvenation of Neutrophil Functions in Association With Reduced Diabetes Risk Following Ten Weeks of Low-Volume High Intensity Interval Walking in Older Adults With Prediabetes - A Pilot Study, In: Frontiers in immunology11pp. 729-729 Frontiers Media

    Neutrophil dysfunction is a common feature of aging, and is associated with the pathogenesis of many age-related diseases, including type 2 diabetes mellitus (T2DM). Although exercise training improves metabolic health, decreases risk of T2DM, and is associated with improving neutrophil functions, involvement in regular physical activity declines with age. The aim of this study was to determine if neutrophil functions could be improved in association with changes in fitness and metabolic parameters in older adults at risk for T2DM using 10-weeks of low volume high-intensity interval exercise training (HIIT). Ten older (71 ± 5 years) sedentary adults with prediabetes (HbA1c: 6.1 ± 0.3%) completed 10 weeks of a supervised HIIT program. Three 30 min sessions/week consisted of ten 60 s intervals of low intensity [50-60% heart rate reserve (HRR)] separated with similar durations of high intensity intervals (80-90% HRR). Before and after training, glucose and insulin sensitivity, neutrophil chemotaxis, bacterial phagocytosis, reactive oxygen species (ROS) production, and mitochondrial functions were assessed. Exercise-mediated changes in cardiorespiratory fitness (VO ) and neutrophil functions were compared to six young (23 ± 1 years) healthy adults. Following training, significant reductions in fasting glucose and insulin were accompanied by improved glucose control and insulin sensitivity (all< 0.05). Before exercise training, VO in the old participants was significantly less than that of the young controls (< 0.001), but increased by 16 ± 11% following training ( = 0.002) resulting in a 6% improvement of the deficit. Neutrophil chemotaxis, phagocytosis and stimulated ROS production were significantly less than that of the young controls, while basal ROS were higher before training (all< 0.05). Following training, chemotaxis, phagocytosis and stimulated ROS increased while basal ROS decreased, similar to levels observed in the young controls (all< 0.05) and reducing the deficit of the young controls between 2 and 154%. In five of the adults with prediabetes, neutrophil mitochondrial functions were significantly poorer than the six young controls before training. Following training, mitochondrial functions improved toward those observed in young controls (all< 0.05), reducing the deficit of the young controls between 14.3 and 451%. Ten weeks of HIIT in older adults at risk for T2DM reduced disease risk accompanied by improved primary and bioenergetic neutrophil functions. Our results are consistent with a reduced risk of infections mediated by relationships in exercise induced systemic and cellular metabolic features. www.ClinicalTrials.gov, identifier NCT02441205, registered on May 12th, 2015.

    Andrea Sitlinger, Danielle M Brander, DAVID BARTLETT (2020)Impact of exercise on the immune system and outcomes in hematologic malignancies, In: Blood advances4(8)pp. 1801-1811 Ash publications

    Exercise is increasingly recognized as important to cancer care. The biology of how exercise improves outcomes is not well understood, however. Studies show that exercise favorably influences the immune system in healthy individuals (neutrophils, monocytes, natural killer cells, T cells, and a number of cytokines). Thus, exercise in patients with hematologic cancer could significantly improve immune function and tumor microenvironment. We performed a literature search and identified 7 studies examining exercise and the immune environment in hematologic malignancies. This review focuses on the role of exercise and physical activity on the immune system in hematologic malignancies and healthy adults.

    DAVID BARTLETT, Niharika A Duggal (2020)Moderate physical activity associated with a higher naïve/memory T-cell ratio in healthy old individuals: potential role of IL15, In: Age and ageing49(3)pp. 368-373 Oxford University Press

    Abstract Introduction ageing is accompanied by impairments in immune responses due to remodelling of the immune system (immunesenescence). Additionally, a decline in habitual physical activity has been reported in older adults. We have recently published that specific features of immunesenescence, such as thymic involution and naïve/memory T-cell ratio, are prevented by maintenance of a high level of physical activity. This study compares immune ageing between sedentary and physically active older adults. Methods a cross-sectional study recruited 211 healthy older adults (60–79 years) and assessed their physical activity levels using an actigraph. We compared T- and B-cell immune parameters between relatively sedentary (n = 25) taking 2,000–4,500 steps/day and more physically active older adults (n = 25) taking 10,500–15,000 steps/day. Results we found a higher frequency of naïve CD4 (P = 0.01) and CD8 (P = 0.02) and a lower frequency of memory CD4 cells (P = 0.01) and CD8 (P = 0.04) T cells in the physically active group compared with the sedentary group. Elevated serum IL7 (P = 0.03) and IL15 (P = 0.003), cytokines that play an essential role in T-cell survival, were seen in the physically active group. Interestingly, a positive association was observed between IL15 levels and peripheral CD4 naïve T-cell frequency (P = 0.023). Discussion we conclude that a moderate level of physical activity may be required to give a very broad suppression of immune ageing, though 10,500–15,000 steps/day has a beneficial effect on the naïve T-cell pool.

    Wayne W Campbell, William E Kraus, Kenneth E Powell, William L Haskell, Kathleen F Janz, John M Jakicic, Richard P Troiano, Kyle Sprow, AG Torres, Katrina L Piercy, DAVID BARTLETT (2019)High-Intensity Interval Training for Cardiometabolic Disease Prevention, In: Medicine and science in sports and exercise51(6)pp. 1220-1226 ACSM

    The 2018 Physical Activity Guidelines Advisory Committee systematically searched existing literature reviews to assess the relationship between high-intensity interval training (HIIT) and reduction in cardiometabolic disease risk. Duplicate independent screenings of 260 articles identified from PubMed®, Cochrane Library, and CINAHL databases yielded suitable data from one systematic review and two meta-analyses. Search terms included a combination of "high intensity" "physical activity/exercise" and "interval training" and outcome-specific terms. The quality of the included reviews was assessed using a tailored version of the AMSTARExBP report on quality. Exposure Subcommittee members graded scientific evidence strength based on a five-criteria rubric and assigned one of four grades: strong, moderate, limited, or not assignable. Moderate evidence indicates that HIIT can improve insulin sensitivity, blood pressure, and body composition in adults with group mean ages ranging from ~20 to ~77 yr. These HIIT-induced improvements in cardiometabolic disease risk factors are comparable with those resulting from moderate-intensity continuous training, and they are more likely to occur in adults at higher risk of cardiovascular disease and diabetes than in healthy adults. Moderate evidence also indicates that adults with overweight or obesity classification are more responsive than adults with normal weight to HIIT-related improvements in insulin sensitivity, blood pressure, and body composition. Insufficient evidence was available to determine whether a dose-response relationship exists between the quantity of HIIT performed and several risk factors for cardiovascular disease and diabetes, or whether the effects of HIIT on cardiometabolic disease risk factors are influenced by age, sex, race/ethnicity, or socioeconomic status. HIIT by adults, especially those with overweight and obesity classification, can improve insulin sensitivity, blood pressure, and body composition, comparable with those resulting from moderate-intensity continuous training.

    David E Lee, Akshay Bareja, DAVID BARTLETT, J White (2019)Autophagy as a Therapeutic Target to Enhance Aged Muscle Regeneration, In: Cells (Basel, Switzerland)8(2) MDPI

    Skeletal muscle has remarkable regenerative capacity, relying on precise coordination between resident muscle stem cells (satellite cells) and the immune system. The age-related decline in skeletal muscle regenerative capacity contributes to the onset of sarcopenia, prolonged hospitalization, and loss of autonomy. Although several age-sensitive pathways have been identified, further investigation is needed to define targets of cellular dysfunction. Autophagy, a process of cellular catabolism, is emerging as a key regulator of muscle regeneration affecting stem cell, immune cell, and myofiber function. Muscle stem cell senescence is associated with a suppression of autophagy during key phases of the regenerative program. Macrophages, a key immune cell involved in muscle repair, also rely on autophagy to aid in tissue repair. This review will focus on the role of autophagy in various aspects of the regenerative program, including adult skeletal muscle stem cells, monocytes/macrophages, and corresponding age-associated dysfunction. Furthermore, we will highlight rejuvenation strategies that alter autophagy to improve muscle regenerative function.

    Brian J Andonian, DAVID BARTLETT, Janet L Huebner, Leslie H Willis, Andrew Hoselton, Virginia B Kraus, William E Kraus, Kim M Huffman (2018)Effect of high-intensity interval training on muscle remodeling in rheumatoid arthritis compared to prediabetes, In: Arthritis research & therapy20(1)pp. 283-283 BioMed Central
    Jacob L Barber, William E Kraus, Timothy S Church, James M Hagberg, Paul D Thompson, DAVID BARTLETT, Michael W Beets, Conrad P Earnest, Kim M Huffman, Rian Q Landers-Ramos, Arthur S Leon, D.C Rao, Richard L Seip, J Skinner, Cris A Slentz, Kenneth R Wilund, Claude Bouchard, Mark A Sarzynski (2018)Effects of regular endurance exercise on GlycA: Combined analysis of 14 exercise interventions, In: Atherosclerosis277pp. 1-6 Elsevier B.V

    GlycA is a relatively new biomarker for inflammation as well as cardiometabolic disease risk. However, the effect of exercise on GlycA is largely unknown. Therefore, the purpose of this study was to examine the effects of regular exercise on the inflammatory marker GlycA across seven studies and 14 exercise interventions. Nuclear magnetic resonance spectroscopy, specifically signal amplitudes originating from the N-acetyl methyl group protons of the N-acetylglucosamine residues on the glycan branches of glycoproteins, was used to quantify GlycA concentrations. GlycA was measured before and after completion of an exercise intervention in 1568 individuals across seven studies and 14 exercise interventions. Random effects inverse variance weighting models were used to pool effects across interventions. Combined analysis of unadjusted data showed that regular exercise significantly (p = 2 × 10−6) reduced plasma GlycA (−8.26 ± 1.8 μmol/L). This reduction remained significant (−9.12 ± 1.9 μmol/L, p = 1.22 × 10−6) following adjustment for age, sex, race, baseline BMI, and baseline GlycA. Changes in GlycA were correlated with changes in traditional inflammatory markers, C-reactive protein, interleukin-6, and fibrinogen, however, these correlations were relatively weak (range r: 0.21–0.38, p 

    DAVID BARTLETT, Leslie H Willis, Cris A Slentz, Andrew Hoselton, Leslie Kelly, Janet L Huebner, Virginia B Kraus, Jennifer Moss, Michael J Muehlbauer, Guillaume Spielmann, William E Kraus, J Lord, Kim M Huffman (2018)Ten weeks of high-intensity interval walk training is associated with reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis: a pilot study, In: Arthritis research & therapy20(1)pp. 127-127 BioMed Central
    Erik D Hanson, Eli Danson, Catriona V Nguyen-Robertson, Jackson J Fyfe, Nigel K Stepto, DAVID BARTLETT, Samy Sakkal (2017)Maximal exercise increases mucosal associated invariant T cell frequency and number in healthy young men, In: European journal of applied physiology117(11)pp. 2159-2169

    Mucosal associated invariant T (MAIT) cells have properties of the innate and acquired immune systems. While the response to vigorous exercise has been established for most leukocytes, MAIT cells have not been investigated. Therefore, the purpose was to determine if MAIT cell lymphocytosis occurs with acute maximal aerobic exercise and if this response is influenced by exercise duration, cardiovascular fitness, or body composition. Twenty healthy young males with moderate fitness levels performed an extended graded exercise test until volitional fatigue. Peripheral blood mononuclear cells were isolated from venous blood obtained prior and immediately after exercise and were labeled to identify specific T cell populations using flow cytometry. The percentage of MAIT cells relative to total T cells significantly increased from 3.0 to 3.8% and absolute MAIT cell counts increased by 2.2-fold following maximal exercise. MAIT cell subpopulation proportions were unchanged with exercise. Within cytotoxic T lymphocytes (CTL), MAIT cells consisted of 8% of these cells and this remained constant after exercise. MAIT cell counts and changes with exercise were not affected by body composition, VO , or exercise duration. Maximal exercise doubled MAIT cell numbers and showed preferential mobilization within total T cells but the response was not influenced by fitness levels, exercise duration, or body composition. These results suggest that acute exercise could be used to offset MAIT cell deficiencies observed with certain pathologies. MAIT cells also make up a substantial proportion of CTLs, which may have implications for cytotoxicity assays using these cells.

    DAVID BARTLETT, Sam O Shepherd, Oliver J Wilson, Ahmed M Adlan, Anton J.M Wagenmakers, Christopher S Shaw, J Lord (2017)Neutrophil and Monocyte Bactericidal Responses to 10 Weeks of Low-Volume High-Intensity Interval or Moderate-Intensity Continuous Training in Sedentary Adults, In: Oxidative medicine and cellular longevity20178148742

    Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on immune function in sedentary adults. Twenty-seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO ), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function.

    G McNee, K L Eales, W Wei, D S Williams, A Barkhuizen, DAVID BARTLETT, S Essex, S Anandram, A Filer, P A H Moss, G Pratt, S Basu, COLIN DAVIES, D A Tennant (2017)Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma, In: Leukemia31(2)pp. 373-381

    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.

    DAVID BARTLETT, O. D. Fox, Clare L McNulty, Hannah L Greenwood, LA Murphy, Elizabeth Sapey, MT Goodman, NJ Crabtree, Cecilie Thøgersen-Ntoumani, James P Fisher, Anton J.M Wagenmakers, J Lord (2016)Habitual physical activity is associated with the maintenance of neutrophil migratory dynamics in healthy older adults, In: Brain, behavior, and immunity56pp. 12-20 Elsevier Inc

    •Physical activity associates with neutrophil migration in the elderly.•Effects occur independently of inflammation or surface receptor expression.•Adiponectin levels may positively influence neutrophil migration. 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 (p0.05). The young group had lower concentrations of IL-6, IL-8, MCP-1, CRP, IL-10 and IL-13 (p

    C Ludwig, D S Williams, DAVID BARTLETT, S Essex, G McNee, J Allwood, E Jewell, A Barkhuisen, H Parry, S Anandram, P Nicolson, C Gardener, F Seymour, S Basu, Warwick B. Dunn, P A H Moss, G Pratt, D A Tennant (2015)Alterations in bone marrow metabolism are an early and consistent feature during the development of MGUS and multiple myeloma, In: Blood cancer journal (New York)5(10)e359

    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.

    Richard J Simpson, CA Cosgrove, Meng M Chee, Brian K McFarlin, DAVID BARTLETT, Guillaume Spielmann, Daniel O'Connor, Hanspeter Pircher, PG Shiels (2010)Senescent phenotypes and telomere lengths of peripheral blood T-cells mobilized by acute exercise in humans, In: Exercise immunology review16pp. 40-55

    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.

    Catherine Shneerson, DAVID BARTLETT, J Lord, Nicola Gale (2014)Supporting healthy ageing: Training multi-disciplinary healthcare students, In: European journal of integrative medicine6(1)pp. 104-111 Elsevier GmbH

    Life expectancy in the UK is increasing at a rate of two years per decade and the need to maintain health in older age is a key challenge facing governments across the world. Health systems based on the biomedical model that focuses on cure of specific conditions is ill-suited to the complex needs of older people, and can often fail to be person-centred. An interprofessional education (IPE) approach may offer benefits in undergraduate training. To engage with some of these challenges, an educational event was held at the University of Birmingham and University Hospital Birmingham. The event focused on the roles that multi-disciplinary health and social care teams can play in supporting healthy ageing, using an IPE approach, and by involving patients and the public. Experts from a range of research disciplines and older members of the local community worked collaboratively with healthcare students to explore strategies and priorities for supporting older people to age healthily. An event that brings healthcare students together to learn from both experts in the field and older people provides a rich learning environment. Further work could be done to improve links to social care.

    Daniel Baylis, DAVID BARTLETT, Holly E Syddall, Georgia Ntani, CP Gale, Colin Cooper, J Lord, Asaad Sayer (2013)Immune-endocrine biomarkers as predictors of frailty and mortality: a 10-year longitudinal study in community-dwelling older people, In: AGE35(3)pp. 963-971 Springer Netherlands

    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.

    M Harrison, Paul Davis, Michel G Khouri, DAVID BARTLETT, Rajan T Gupta, A Armstrong, Megan A McNamara, Tian-Ping Zhang, M Anand, Kelly Onyenwoke, Sara Edwardson, Danielle Craig, Meghan Michalski, Yuan Wu, Taofik Oyekunle, Brian Coyne, Aubrie Coburn, Lee W Jones, DJ George (2022)A randomized controlled trial comparing changes in fitness with or without supervised exercise in patients initiated on enzalutamide and androgen deprivation therapy for non-metastatic castration-sensitive prostate cancer (EXTEND), In: Prostate cancer and prostatic diseases Nature

    Androgen deprivation therapy (ADT) and androgen receptor signaling inhibitors (ARSI) are associated with deleterious physical effects, which exercise may mitigate; however, exercise has never been studied in patients initiating treatment with ADT and an ARSI. Our objective was to determine whether supervised exercise prior to and during initial therapy could mitigate adverse effects of ADT plus enzalutamide. We conducted a single center trial in patients with recurrent prostate cancer treated with ADT and enzalutamide. We randomized 26 patients to 16 weeks of supervised exercise (aerobic and resistance), starting 4 weeks before initiation of ADT and enzalutamide, or usual care. The primary endpoint was change in peak oxygen uptake (VO peak) as a measure of cardiorespiratory fitness (CRF). Secondary endpoints were functional capacity, maximal strength, body composition, patient-reported outcomes, safety, and feasibility. Analysis of covariance was used to compare outcomes for groups at Week 17 adjusted for baseline values. The usual care group (N = 13) showed declines from baseline to week 17 in both absolute CRF (-0.31 L/min, -10.9%; p 

    DAVID BARTLETT, Gloria Broadwater, Heidi K White, Rebecca Shelby, Leah L Zullig, J Robertson, Ravindran Kanesvaran, H Cohen, Gretchen Kimmick (2020)Factors associated with falls in older women with breast cancer: the use of a brief geriatric screening tool in clinic, In: Breast cancer research and treatment184(2)pp. 445-457 Springer

    Unintentional falls and breast cancer are common among older women, but the associations between them are understudied. We aimed to identify factors associated with falls in older women with breast cancer. We retrospectively reviewed clinical records of older women with breast cancer at Duke Medical Center who had completed the Senior Adult Oncology Program geriatric assessment. Characteristics were compared between women had had at least one fall in the past year and those who did not. Pearson's Chi-square tests and t tests were used for comparison of groups' characteristics. Logistic regression determined factors associated with falling. We identified 425 women, age 76.2 years (range 65-89 years), at the time of the assessment. 118 (27.8%) women reported a fall in the prior year. Age, race, ethnicity, and time since diagnosis (all p > 0.05) were similar between groups. In univariate analyses, metastatic disease (p = 0.023) and history of endocrine therapy (p = 0.042) were more common among women who fell. Women who fell had lower systolic (p = 0.001), diastolic (p 

    Andrea Sitlinger, Michael A Deal, Erwin Garcia, Dana K Thompson, T Stewart, Grace MacDonald, Nicolas Devos, David Corcoran, Janet S Staats, Jennifer Enzor, Kent J Weinhold, Danielle M Brander, J. Brice Weinberg, DAVID BARTLETT (2021)Physiological Fitness and the Pathophysiology of Chronic Lymphocytic Leukemia (CLL), In: Cells (Basel, Switzerland)10(5) MDPI

    Chronic lymphocytic leukemia (CLL) is associated with physical dysfunction and low overall fitness that predicts poor survival following the commencement of treatment. However, it remains unknown whether higher fitness provides antioncogenic effects. We identified ten fit (CLL-FIT) and ten less fit (CLL-UNFIT) treatment-naïve CLL patients from 144 patients who completed a set of physical fitness and performance tests. Patient plasma was used to determine its effects on an in vitro 5-day growth/viability of three B-cell cell lines (OSU-CLL, Daudi, and Farage). Plasma exosomal miRNA profiles, circulating lipids, lipoproteins, inflammation levels, and immune cell phenotypes were also assessed. CLL-FIT was associated with fewer viable OSU-CLL cells at Day 1 ( p = 0.003), Day 4 ( p = 0.001), and Day 5 ( p = 0.009). No differences between the groups were observed for Daudi and Farage cells. Of 455 distinct exosomal miRNAs identified, 32 miRNAs were significantly different between the groups. Of these, 14 miRNAs had ≤−1 or ≥1 log2 fold differences. CLL-FIT patients had five exosomal miRNAs with lower expression and nine miRNAs with higher expression. CLL-FIT patients had higher HDL cholesterol, lower inflammation, and lower levels of triglyceride components (all p< 0.05). CLL-FIT patients had lower frequencies of low-differentiated NKG2+/CD158a/b neg ( p = 0.015 and p = 0.014) and higher frequencies of NKG2A neg /CD158b+ mature NK cells ( p = 0.047). The absolute number of lymphocytes, including CD19+/CD5+ CLL-cells, was similar between the groups ( p = 0.359). Higher physical fitness in CLL patients is associated with altered CLL-like cell line growth in vitro and with altered circulating and cellular factors indicative of better immune functions and tumor control.

    Erik D Hanson, Lauren C Bates, DAVID BARTLETT, John P Campbell (2021)Does exercise attenuate age- and disease-associated dysfunction in unconventional T cells? Shining a light on overlooked cells in exercise immunology, In: European journal of applied physiology121(7)pp. 1815-1834

    Unconventional T Cells (UTCs) are a unique population of immune cells that links innate and adaptive immunity. Following activation, UTCs contribute to a host of immunological activities, rapidly responding to microbial and viral infections and playing key roles in tumor suppression. Aging and chronic disease both have been shown to adversely affect UTC numbers and function, with increased inflammation, change in body composition, and physical inactivity potentially contributing to the decline. One possibility to augment circulating UTCs is through increased physical activity. Acute exercise is a potent stimulus leading to the mobilization of immune cells while the benefits of exercise training may include anti-inflammatory effects, reductions in fat mass, and improved fitness. We provide an overview of age-related changes in UTCs, along with chronic diseases that are associated with altered UTC number and function. We summarize how UTCs respond to acute exercise and exercise training and discuss potential mechanisms that may lead to improved frequency and function.

    Gurpreet S Baht, Akshay Bareja, David E Lee, Rajesh R Rao, Rong Huang, Janet L Huebner, DAVID BARTLETT, Corey R Hart, Jason R Gibson, Ian R Lanza, Virginia B Kraus, Simon G Gregory, Bruce M Spiegelman, J White (2020)Meteorin-like facilitates skeletal muscle repair through a Stat3/IGF-1 mechanism, In: Nature metabolism2(3)pp. 278-289 Nature

    The immune system plays a multifunctional role throughout the regenerative process, regulating both pro-/anti-inflammatory phases and progenitor cell function. In the present study, we identify the myokine/cytokine Meteorin-like (Metrnl) as a critical regulator of muscle regeneration. Mice genetically lacking Metrnl have impaired muscle regeneration associated with a reduction in immune cell infiltration and an inability to transition towards an anti-inflammatory phenotype. Isochronic parabiosis, joining wild-type and whole-body Metrnl knock-out (KO) mice, returns Metrnl expression in the injured muscle and improves muscle repair, providing supportive evidence for Metrnl secretion from infiltrating immune cells. Macrophage-specific Metrnl KO mice are also deficient in muscle repair. During muscle regeneration, Metrnl works, in part, through Stat3 activation in macrophages, resulting in differentiation to an anti-inflammatory phenotype. With regard to myogenesis, Metrnl induces macrophage-dependent insulin-like growth factor 1 production, which has a direct effect on primary muscle satellite cell proliferation. Perturbations in this pathway inhibit efficacy of Metrnl in the regenerative process. Together, these studies identify Metrnl as an important regulator of muscle regeneration and a potential therapeutic target to enhance tissue repair.

    DAVID BARTLETT, Charlotte M Firth, AC Phillips, Paul Moss, Daniel Baylis, Holly E Syddall, Avan A Sayer, Cyrus Cooper, J Lord (2012)The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection, In: Aging cell11(5)pp. 912-915

    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.

    Brian J Andonian, Alec Koss, Timothy R Koves, E Hauser, Monica J Hubal, David M Pober, J Lord, Nancie J MacIver, E William St Clair, Deborah M Muoio, William E Kraus, David B. Bartlett, Kim M Huffman (2022)Rheumatoid arthritis T cell and muscle oxidative metabolism associate with exercise-induced changes in cardiorespiratory fitness, In: Scientific Reports127450

    Rheumatoid arthritis (RA) T cells drive autoimmune features via metabolic reprogramming that reduces oxidative metabolism. Exercise training improves cardiorespiratory fitness (i.e., systemic oxidative metabolism) and thus may impact RA T cell oxidative metabolic function. In this pilot study of RA participants, we took advantage of heterogeneous responses to a high-intensity interval training (HIIT) exercise program to identify relationships between improvements in cardiorespiratory fitness with changes in peripheral T cell and skeletal muscle oxidative metabolism. In 12 previously sedentary persons with seropositive RA, maximal cardiopulmonary exercise tests, fasting blood, and vastus lateralis biopsies were obtained before and after 10 weeks of HIIT. Following HIIT, improvements in RA cardiorespiratory fitness were associated with changes in RA CD4 + T cell basal and maximal respiration and skeletal muscle carnitine acetyltransferase (CrAT) enzyme activity. Further, changes in CD4 + T cell respiration were associated with changes in naïve CD4 + CCR7 + CD45RA + T cells, muscle CrAT, and muscle medium-chain acylcarnitines and fat oxidation gene expression profiles. In summary, modulation of cardiorespiratory fitness and molecular markers of skeletal muscle oxidative metabolism during exercise training paralleled changes in T cell metabolism. Exercise training that improves RA cardiorespiratory fitness may therefore be valuable in managing pathologically related immune and muscle dysfunction.

    Erik D Hanson, Mohamdod S Alzer, JR Carver, Cameron K Stopforth, Alexander R Lucas, Young E Whang, Matthew I Milowsky, DAVID BARTLETT, M Harrison, Rhonda L Bitting, Allison M Deal, Lee Stoner, A C Hackney, Claudio L Battaglini (2022)Feasibility of home-based exercise training in men with metastatic castration-resistant prostate cancer, In: Prostate cancer and prostatic diseases Nature

    Home-based training increases accessibility to exercise and mitigates the side effects of hormone therapy for prostate cancer (PC). However, it is unknown if men with more advanced disease are willing to partake in such interventions. To determine the feasibility of a home-based exercise intervention in men with metastatic castration-resistant prostate cancer (mCRPC). mCRPC patients on androgen receptor signaling inhibitors (ARSI) were prescribed a 12-week, home-based exercise intervention using resistance bands and walking. Feasibility was assessed using recruitment, retention, adherence, and outcome capture. Physiological changes and patient reported outcomes were assessed before and after the intervention. Of the 62 referrals, 47 were eligible with 22 men performing baseline testing (47% recruitment rate) and 16 completing the intervention (73% retention). Task completion was >86% for all physiological tests. Walking adherence was 80% and resistance training was 63%, the latter falling short of the study target (75%). Training increased thigh muscle cross-sectional area by 22%, time to exhaustion by 19% (both p 

    Brian J Andonian, Andrew Johannemann, Monica J Hubal, David M Pober, Alec Koss, William E Kraus, DAVID BARTLETT, Kim M Huffman (2021)Altered skeletal muscle metabolic pathways, age, systemic inflammation, and low cardiorespiratory fitness associate with improvements in disease activity following high-intensity interval training in persons with rheumatoid arthritis, In: Arthritis research & therapy23(1)pp. 1-187 BioMed Central
    Erik D Hanson, Lauren C Bates, Elizabeth P Harrell, DAVID BARTLETT, Jordan T Lee, Chad W Wagoner, Mohamdod S Alzer, Dean J Amatuli, Brian C Jensen, Allison M Deal, Hyman B Muss, Kirsten A Nyrop, Claudio L Battaglini (2021)Exercise training partially rescues impaired mucosal associated invariant t-cell mobilization in breast cancer survivors compared to healthy older women, In: Experimental gerontology152111454 Elsevier Inc

    Exercise may attenuate immunosenescence with aging that appears to be accelerated following breast cancer treatment, although limited data on specific cell types exists and acute and chronic exercise have been investigated independently in older adults. To determine the mucosal associated invariant T (MAIT) cell response to acute exercise before (PRE) and after (POST) 16 weeks of exercise training in breast cancer survivors (BCS) and healthy older women (CON). Age-matched BCS and CON performed 45 min of intermittent cycling at 60% peak power output wattage. Blood samples were obtained at rest, immediately (0 h) and 1 h after exercise to determine MAIT cell counts, frequency, and intracellular cytokine expression. At PRE, MAIT cell counts were greater in CON (137%) than BCS at 0 h (46%, p 

    Erik D Hanson, Cameron K Stopforth, Mohamdod S Alzer, JR Carver, Alexander R Lucas, Young E Whang, Matthew I Milowsky, DAVID BARTLETT, M Harrison, A Hayes, Rhonda L Bitting, Allison M Deal, A C Hackney, Claudio L Battaglini (2021)Body composition, physical function and quality of life in healthy men and across different stages of prostate cancer, In: Prostate cancer and prostatic diseases24(3)pp. 725-732

    Androgen deprivation therapy (ADT) for prostate cancer (PC) has detrimental effects on physical function and quality of life (QoL), but the addition of androgen receptor signalling inhibitors (ARSI) on these outcomes is unclear. To compare body composition, physical function, and QoL across progressive stages of PC and non-cancer controls (CON). In men with hormone sensitive PC (HSPC, n = 43) or metastatic castration-resistant PC (mCRPC, n = 22) or CON (n = 37), relative and absolute lean and fat mass, physical function (6 m walk, chair stands, timed up and go [TUG], stair climb), and QoL were determined. Relative body composition differed amongst all groups, along with ~39% greater absolute fat mass in mCRPC vs. CON. TUG and chair stands were ~71% and ~33% slower in mCRPC compared to both CON and HSPC, whereas stair climb was ~29% and 6 m walk was ~18% slower in mCRPC vs. CON. Relative body composition was correlated with physical function (r = 0.259-0.385). Clinically relevant differences for mCRPC were observed for overall QoL and several subscales vs. CON, although body composition and physical function did not influence QoL. PC progression is associated with deteriorations in body composition and physical function. As ADT length was similar between groups, ARSI use for mCRPC likely contributed in part to these changes. Given the difficulties of improving lean mass during ADT, interventions that reduce adiposity may lessen the side effects of hormone therapy.

    Erik D Hanson, Samy Sakkal, Shadney Que, Eunhan Cho, Guillaume Spielmann, Elif Kadife, John A Violet, Claudio L Battaglini, Lee Stoner, DAVID BARTLETT, Glenn K McConell, A Hayes (2020)Natural killer cell mobilization and egress following acute exercise in men with prostate cancer, In: Experimental physiology105(9)pp. 1524-1539 Wiley

    New Findings What is the central question of this study? What are the characteristics of the NK cell response following acute moderate‐intensity aerobic exercise in prostate cancer survivors and is there a relationship between stress hormones and NK cell mobilization? What is the main finding and its importance? NK cell numbers and proportions changed similarly between prostate cancer survivors and controls following acute exercise. Consecutive training sessions can likely be used without adverse effects on the immune system during prostate cancer treatment. Prostate cancer treatment affects multiple physiological systems, although the immune response during exercise has been minimally investigated. The objective was to characterize the natural killer (NK) cell response following acute exercise in prostate cancer survivors. Prostate cancer survivors on androgen deprivation therapy (ADT) and those without (PCa) along with non‐cancer controls (CON) completed a moderate intensity cycling bout. NK cells were phenotyped before and 0, 2 and 24 h after acute exercise using flow cytometry. CD56 total NK cell frequency increased by 6.2% at 0 h (P 

    DAVID BARTLETT, Cris A Slentz, Margery A Connelly, Lucy W Piner, Leslie H Willis, Lori A Bateman, Esther O Granville, Connie W Bales, Kim M Huffman, William E Kraus (2017)Association of the Composite Inflammatory Biomarker GlycA, with Exercise-Induced Changes in Body Habitus in Men and Women with Prediabetes, In: Oxidative medicine and cellular longevity2017pp. 1-12

    GlycA is a new composite measure of systemic inflammation and a predictor of many inflammatory diseases. GlycA is the nuclear magnetic resonance spectroscopy-derived signal arising from glucosamine residues on acute-phase proteins. This study aimed to evaluate how exercise-based lifestyle interventions modulate GlycA in persons at risk for type 2 diabetes. GlycA, fitness, and body habitus were measured in 169 sedentary adults (45–75 years) with prediabetes randomly assigned to one of four six-month exercise-based lifestyle interventions. Interventions included exercise prescription based on the amount (energy expenditure (kcal/kg weight/week (KKW)) and intensity (%VO2peak). The groups were (1) low-amount/moderate-intensity (10KKW/50%) exercise; (2) high-amount/moderate-intensity (16KKW/50%) exercise; (3) high-amount/vigorous-intensity (16KKW/75%) exercise; and (4) a Clinical Lifestyle (combined diet plus low-amount/moderate-intensity exercise) intervention. Six months of exercise training and/or diet-reduced GlycA (mean Δ: −6.8 ± 29.2 μmol/L;p=0.006) and increased VO2peak(mean Δ: 1.98 ± 2.6 mL/kg/min;p

    Ana Vitlic, J Lord, Angela E Taylor, W Arlt, DAVID BARTLETT, A Rossi, Niharika Arora-Duggal, A. Welham, M. Heald, C. Oliver, DL Carroll, AC Phillips (2016)Neutrophil function in young and old caregivers, In: British journal of health psychology21(1)pp. 173-189

    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.

    DAVID BARTLETT, Margery A Connelly, Hiba AbouAssi, Lori A Bateman, K Noelle Tune, Janet L Huebner, Virginia B Kraus, Deborah A Winegar, James D Otvos, William E Kraus, Kim M Huffman (2016)A novel inflammatory biomarker, GlycA, associates with disease activity in rheumatoid arthritis and cardio-metabolic risk in BMI-matched controls, In: Arthritis research & therapy18(1)pp. 86-86 BMC

    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 

    Daniel Baylis, Georgia Ntani, Mark H Edwards, Holly E Syddall, DAVID BARTLETT, Elaine M Dennison, Carmen Martin-Ruiz, Thomas von Zglinicki, D Kuh, J Lord, Avan Aihie Sayer, Cyrus Cooper (2014)Inflammation, Telomere Length, and Grip Strength: A 10-year Longitudinal Study, In: Calcified tissue international95(1)pp. 54-63 Springer US

    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]-1 β : β  = −2.18, p  = 0.001). However, these associations were maintained when adjusted for telomere attrition (IL-1 β , 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.

    Daniel Baylis, DAVID BARTLETT, Harnish P Patel, Helen C Roberts (2013)Understanding how we age: insights into inflammaging, In: Longevity & healthspan2(1)pp. 8-8 BioMed Central

    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.