title: Aerobic exercise reverses arterial inflammation with aging in mice.
abstract: We tested the hypothesis that regular aerobic exercise reverses arterial inflammation with aging. When compared with young controls (6.2 ± 0.4 mo; n = 7), old (31.3 ± 0.5 mo; n = 11) male B6D2F1 cage-restricted mice demonstrated increased arterial activation of the proinflammatory transcription factor NF-κB, as indicated by greater aortic phosphorylation of both the inhibitor of NF-κB kinase (IKK) and the p65 subunit of NF-κB (both P < 0.05). Similarly, aortic expression of the proinflammatory cytokines IL-1 and IL-6, IFN-γ, and TNF-α were greater in the old mice (all P < 0.05). Macrophage and T lymphocyte abundance was unchanged with age in the aortic intima and media but was markedly increased in the adventitia and perivascular fat tissue of old mice (all P < 0.05). This proinflammatory arterial phenotype with aging was associated with vascular dysfunction, as reflected by impaired nitric oxide-mediated endothelium-dependent dilation. Voluntary wheel running (10-14 wk) normalized aortic IKK-NF-κB activation, cytokine expression, adventitial and perivascular macrophage infiltration, and vascular function in old mice (32.4 ± 0.3 mo; n = 8) while having no consistent effects in young mice. Short-term voluntary wheel running started late in life reverses arterial inflammation with aging in mice possibly via outside-in actions. These anti-inflammatory effects may play an important role in the amelioration of age-associated vascular dysfunction by regular aerobic exercise.
authors.affiliation: Department of Integrative Physiology, University of Colorado at Boulder, Boulder, Colorado, USA. Lisa.Lesniewski@utah.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lesniewski
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Durrant
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Connell
authors.forename: Grant D
authors.initials: GD
authors.lastname: Henson
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Black
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000367:Age Factors; D000375:Aging / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000276:immunology*; D001025:Aortitis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D001167:Arteritis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D002339:Carotid Arteries / Q000276:immunology* / Q000503:physiopathology; D051550:I-kappa B Kinase / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016018:Least-Squares Analysis; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D010641:Phenotype; D010766:Phosphorylation; D005082:Physical Exertion; D013601:T-Lymphocytes / Q000276:immunology; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014664:Vasodilation
chemical_list: D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase