Impaired plasma nitric oxide availability and extracellular superoxide dismutase activity in healthy humans with advancing age.
Level 4 - case-series / case-control
Cross-sectional observational study evaluating circulating biomarkers across age
PubMed 16214176 · doi:10.1016/j.lfs.2005.06.037
What was done
Fasting plasma samples were collected from 40 healthy men aged 20 to 92 years. The researchers measured plasma stable end-product nitrite/nitrate (NOx) to assess nitric oxide availability, extracellular superoxide dismutase (EC-SOD) activity, thiobarbituric acid reactive substances (TBARS) for lipid peroxidation, Trolox equivalent antioxidant capacity (TEAC) for total antioxidant capacity, and in vitro low-density lipoprotein (LDL) susceptibility to copper-mediated oxidation (measured as lag time).
What was found
Advancing age significantly correlated with lower plasma NOx (r = -0.877, P < 0.001), decreased EC-SOD activity (r = -0.888, P < 0.001), decreased TEAC (r = -0.647, P < 0.001), and shorter LDL lag time (r = -0.621, P < 0.001). Age also correlated with increased plasma TBARS (r = 0.858, P < 0.001). In multivariable analysis, plasma NOx levels were independently predicted by EC-SOD activity and age, while EC-SOD activity was predicted by age and TEAC.
Why it matters
These findings suggest that an age-related loss of extracellular antioxidant defense (EC-SOD) contributes directly to the decline in systemic nitric oxide availability, offering a biochemical mechanism for age-associated endothelial dysfunction.
Limits
The study is limited by a small sample size (n = 40) restricted entirely to men, preventing generalization to women. The cross-sectional design demonstrates correlation rather than causation, and measurements relied on plasma surrogate markers rather than direct vascular or functional endothelial assessments.
Cited by
- supports Endothelial production of nitric oxide in the human body significantly declines by approximately age 40.