Open AccessLife‐long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice
Author(s) -
Donato Anthony J.,
Walker Ashley E.,
Magerko Katherine A.,
Bramwell R. Colton,
Black Alex D.,
Henson Grant D.,
Lawson Brooke R.,
Lesniewski Lisa A.,
Seals Douglas R.
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12103
Subject(s) - arterial stiffness , oxidative stress , medicine , pulse wave velocity , endocrinology , nitrotyrosine , nitric oxide , superoxide dismutase , endothelial dysfunction , blood pressure , endothelium , biology , nitric oxide synthase
Summary 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 ( O ld AL : 30–31 month) and life‐long 40% CR old (30–31 month) B 6 D 2F1 mice. Blood pressure was elevated with aging ( P < 0.05) and was blunted by CR ( P < 0.05 vs. O ld AL ). PWV was 27% greater in old vs. young AL ‐fed mice ( P < 0.05), and CR prevented this increase ( P < 0.05 vs. O ld 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. O ld 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 O ld CR vs. Old AL ). Lastly, CR normalized age‐related changes in the critical nutrient‐sensing pathways SIRT ‐1 and m TOR ( P < 0.05 vs. O ld AL ). Our findings demonstrate that CR is an effective strategy for attenuation of arterial aging.