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.

Aerobic exercise training increases plasma Klotho levels and reduces arterial stiffness in postmenopausal women

“…An exercise training-induced increase in Klotho may modulate the production of TGF-␤1 and ET-1. Furthermore, several studies have suggested that the mechanisms underlying aerobic exercise training-induced modulation of arterial stiffness were mediated by the enhancement of endothelial function, suppression of oxidative stress, and inflammation (24,27,46). Therefore, an exercise training-induced increase in plasma Klotho levels might act on the endothelium to increase NO production, calcium channels in endothelial cells to regulate calcium influx, endothelial cells to suppress inflammation, and smooth muscle cells to suppress oxidative stress.…”

“…Furthermore, habitual aerobic exercise decreases arterial stiffness in middle-aged and elderly individuals and postmenopausal women (45,47). Several reports have suggested that the mechanisms by which aerobic exercise training decreases the arterial stiffness could be partly mediated by the enhancement of endothelial function, suppression of oxidative stress, and inflammation (24,27,46). However, the precise mechanism underlying the aerobic exercise-induced modulation of arterial stiffness remains unclear.…”

Contribution of receptor for advanced glycation end products to vasculature-protecting effects of exercise training in aged rats

“…Suppression of oxidative stress and inflammation is the hallmark of the health-beneficial effects of exercise training (Lesniewski et al, 2011;Ji et al, 1998). However, the molecular mechanisms of exercise action on oxidative stress and inflammation remain elusive.…”

TNF-α impairs endothelial function in adipose tissue resistance arteries of mice with diet-induced obesity

“…Positive staining was visualized with 3,3=-diaminobenzidine (K4011; Dako), and sections were counterstained with Mayer's hematoxylin (S3309; Dako) to identify nuclei. Using ImageJ 1.42, a technician blinded to group identity outlined the adventitia with a pen tablet (Bamboo Fun; Wacom) and counted the total number of nuclei and the number of nuclei with positive staining for macrophages (23 Vascular function. To assess endothelial function, arteries were excised, cleared of surrounding adipocytes, and cannulated in the stage of a pressure myograph (DMT).…”