Research Paper Volume 8, Issue 11 pp 2897—2914

Voluntary aerobic exercise increases arterial resilience and mitochondrial health with aging in mice

Rachel A. Gioscia-Ryan1, , Micah L. Battson1, , Lauren M. Cuevas1, , Melanie C. Zigler1, , Amy L. Sindler1, , Douglas R. Seals1, ,

  • 1 Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA

Received: July 3, 2016       Accepted: November 3, 2016       Published: November 22, 2016
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Mitochondrial dysregulation and associated excessive reactive oxygen species (mtROS) production is a key source of oxidative stress in aging arteries that reduces baseline function and may influence resilience (ability to withstand stress). We hypothesized that voluntary aerobic exercise would increase arterial resilience in old mice. An acute mitochondrial stressor (rotenone) caused greater (further) impairment in peak carotid EDD in old (~27 mo., OC, n=12; -32.5±-10.5%) versus young (~7 mo., YC n=11; -5.4±- 3.7%) control male mice, whereas arteries from young and old exercising (YVR n=10 and OVR n=11, 10-wk voluntary running; -0.8±-2.1% and -8.0±4.9%, respectively) mice were protected. Ex-vivo simulated Western diet (WD, high glucose and palmitate) caused greater impairment in EDD in OC (-28.5±8.6%) versus YC (-16.9±5.2%) and YVR (-15.3±2.3%), whereas OVR (-8.9±3.9%) were more resilient (not different versus YC). Simultaneous ex-vivo treatment with mitochondria-specific antioxidant MitoQ attenuated WD-induced impairments in YC and OC, but not YVR or OVR, suggesting that exercise improved resilience to mtROS-mediated stress. Exercise normalized age-related alterations in aortic mitochondrial protein markers PGC-1α, SIRT-3 and Fis1 and augmented cellular antioxidant and stress response proteins. Our results indicate that arterial aging is accompanied by reduced resilience and mitochondrial health, which are restored by voluntary aerobic exercise.


ACh: acetylcholine; CVD: cardiovascular diseases; EDD: endothelium-dependent dilation; eNOS: endothelial nitric oxide synthase; Hsp: heat shock protein; LDL: low-density lipoprotein; mtROS: mitochondria-derived reactive oxygen species; NO: nitric oxide; OC: old control mice; OVR: old voluntary wheel running mice; OXPHOS: oxidative phosphorylation; PGC-1α: peroxisome proliferator-activated receptor gamma co-activator 1-alpha; SIRT-3: NAD-dependent deacetylase sirtuin-3; SNP: sodium nitroprusside; YC: young control mice; YVR: young voluntary wheel running mice.