title: Voluntary aerobic exercise increases arterial resilience and mitochondrial health with aging in mice.
abstract: 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-vivosimulated 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). Simultaneousex-vivotreatment 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.
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Gioscia-Ryan
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Micah L
authors.initials: ML
authors.lastname: Battson
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Cuevas
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Melanie C
authors.initials: MC
authors.lastname: Zigler
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Sindler
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, USA.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002339:Carotid Arteries / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D017382:Reactive Oxygen Species; D014652:Vascular Diseases / Q000503:physiopathology / Q000517:prevention & control; D059289:Vascular Stiffness
chemical_list: D000975:Antioxidants; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species
keywords: exercise; mitochondria; vascular function