title: Life-long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice.
abstract: Aging impairs arterial function through oxidative stress and diminished nitric oxide (NO) bioavailability. Life-long caloric restriction (CR) reduces oxidative stress, but its impact on arterial aging is incompletely understood. We tested the hypothesis that life-long CR attenuates key features of arterial aging. Blood pressure, pulse wave velocity (PWV, arterial stiffness), carotid artery wall thickness and endothelium-dependent dilation (EDD; endothelial function) were assessed in young (Y: 5-7 month), old ad libitum (Old AL: 30-31 month) and life-long 40% CR old (30-31 month) B6D2F1 mice. Blood pressure was elevated with aging (P < 0.05) and was blunted by CR (P < 0.05 vs. Old AL). PWV was 27% greater in old vs. young AL-fed mice (P < 0.05), and CR prevented this increase (P < 0.05 vs. Old AL). Carotid wall thickness was greater with age (P < 0.05), and CR reduced this by 30%. CR effects were associated with amelioration of age-related changes in aortic collagen and elastin. Nitrotyrosine, a marker of cellular oxidative stress, and superoxide production were greater in old AL vs. young (P < 0.05) and CR attenuated these increase. Carotid artery EDD was impaired with age (P < 0.05); CR prevented this by enhancing NO and reducing superoxide-dependent suppression of EDD (Both P < 0.05 vs. Old AL). This was associated with a blunted age-related increase in NADPH oxidase activity and p67 expression, with increases in superoxide dismutase (SOD), total SOD, and catalase activities (All P < 0.05 Old CR vs. Old AL). Lastly, CR normalized age-related changes in the critical nutrient-sensing pathways SIRT-1 and mTOR (P < 0.05 vs. Old AL). Our findings demonstrate that CR is an effective strategy for attenuation of arterial aging.
authors.affiliation: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA, USA; Department of Internal Medicine, Division of Geriatrics, University of Utah, Salt Lake City, UT, USA; Veteran's Affairs Medical Center-Salt Lake City, Geriatrics Research Education and Clinical Center, Salt Lake City, UT, USA; Department of Exercise and Sports Science, University of Utah, Salt Lake City, UT, USA.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Walker
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Magerko
authors.forename: R Colton
authors.initials: RC
authors.lastname: Bramwell
authors.forename: Alex D
authors.initials: AD
authors.lastname: Black
authors.forename: Grant D
authors.initials: GD
authors.lastname: Henson
authors.forename: Brooke R
authors.initials: BR
authors.lastname: Lawson
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lesniewski
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D001158:Arteries / Q000378:metabolism*; D001682:Biological Availability; D001794:Blood Pressure / Q000502:physiology; D031204:Caloric Restriction; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D059289:Vascular Stiffness / Q000502:physiology
chemical_list: D013481:Superoxides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III
keywords: aging; arteries; calorie restriction; oxidative stress