title: Habitual physical activity is associated with the maintenance of neutrophil migratory dynamics in healthy older adults.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.affiliation: MRC-ARUK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, United Kingdom. Electronic address: d.b.bartlett@bham.ac.uk.
authors.forename: David B
authors.initials: DB
authors.lastname: Bartlett
authors.affiliation: MRC-ARUK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Oliver
authors.initials: O
authors.lastname: Fox
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Clare L
authors.initials: CL
authors.lastname: McNulty
authors.affiliation: MRC-ARUK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Greenwood
authors.affiliation: MRC-ARUK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Murphy
authors.affiliation: MRC-ARUK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sapey
authors.affiliation: Geriatric Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2WB, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Goodman
authors.affiliation: NIHR/Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital, Birmingham B15 2WB, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Crabtree
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Thøgersen-Ntoumani
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: James P
authors.initials: JP
authors.lastname: Fisher
authors.affiliation: Research Institute for Sport & Exercise Sciences, Liverpool John Moores University, Liverpool L3 3AF, United Kingdom.
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: Wagenmakers
authors.affiliation: MRC-ARUK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, United Kingdom.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Lord
mesh_terms: D000368:Aged; D000375:Aging / Q000097:blood / Q000276:immunology / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D000068884:Immunosenescence / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000502:physiology*
keywords: Ageing; Immunosenescence; Inflammation; Innate immunity; Migration; Neutrophil; Physical activity