As people get older, their blood vessels have a harder time relaxing because they produce less of a helpful chemical called nitric oxide, which makes it tougher for blood to flow freely — this is one reason why older adults are more likely to have heart and blood vessel problems.

Measure eNOS activity and nitric oxide bioavailability in healthy individuals across a wide age range (e.g., 20–80 years) and correlate these levels with direct measures of vasodilation (e.g., flow-mediated dilation) and endothelial dysfunction markers (e.g., adhesion molecules) in the same subjects.

Track eNOS activity and nitric oxide levels over time in the same individuals as they age, and determine whether declines in these markers predict the onset of impaired vasodilation and clinical endothelial dysfunction.

Compare eNOS activity and nitric oxide levels in individuals with diagnosed age-related vascular disease versus age-matched healthy controls to determine if reduced levels are consistently present in those with endothelial dysfunction.

Measure age-related changes in eNOS activity and nitric oxide bioavailability in a controlled animal model (e.g., C57BL/6 mice) and correlate with vascular function over the lifespan.

Use human endothelial cells in culture subjected to replicative senescence or oxidative stress to model aging and assess changes in eNOS activity and nitric oxide production.