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Extracellular Superoxide Dismutase Activity is Reduced with Aging in Humans: Relation to Impaired Vascular Endothelial Function and Exercise Capacity
Author(s) -
LaRocca Thomas J.,
Seals Douglas R.,
Walker Ashley E.,
Eskurza Iratxe,
Pierce Gary L.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.777.8
Subject(s) - endocrinology , superoxide dismutase , medicine , oxidative stress , endothelium , nitric oxide , superoxide , dismutase , endothelial dysfunction , chemistry , extracellular , biochemistry , enzyme
Aging is associated with impaired exercise capacity and vascular endothelium‐dependent dilation (EDD), the latter mediated by oxidative stress and reduced nitric oxide (NO ? ) bioavailability. The antioxidant enzyme extracellular superoxide dismutase (EC‐SOD) binds to the endothelial wall via a heparin binding domain and protects NO ? from inactivation by superoxide (O 2 ?− ). However, the effects of aging on EC‐SOD and its relation to EDD and exercise capacity are unknown. Two groups of healthy non‐obese adults were studied: young sedentary (YS: n = 7; age 22 ± 2 yr; 2M) and older sedentary (OS: n = 12; 62 ± 2 yr; 6M). EDD (brachial artery flow‐mediated dilation) was lower (P < 0.05) in OS (5.4 ± 0.7 Δ%) vs. YS (7.4 ± 0.9 Δ%). EC‐SOD activity, measured by the release of EC‐SOD into plasma following intravenous heparin bolus (5000U), also was lower (P < 0.01) in OS vs. YS (AUC 15min : 5.4 ± 1.4 vs. 14.0 ± 1.7 U/mL/min). EC‐SOD activity was inversely related to age (r = ‐0.61, P < 0.01) and positively related to EDD (r = 0.64, P < 0.01) and exercise capacity (maximal oxygen consumption, r = 0.50, P < 0.05). EC‐SOD activity was inversely related to plasma oxidized low‐density lipoprotein (r = ‐0.44, P < 0.05), a circulating marker of oxidative stress, but not to any other anthropometric or metabolic risk factor. These results provide the first evidence that EC‐SOD activity is reduced with aging in healthy humans and may contribute to oxidative stress‐associated vascular endothelial dysfunction and impaired exercise capacity. NIH AG000279 , AG013038 , AG022241 , AG006537 , RR00051