Aging increases circulating BH₂ without modifying BH₄ levels and impairs peripheral vascular function in healthy...

Area of Science:

• Vascular Biology
• Aging Research
• Biochemistry

Background:

• Mechanisms of vascular aging and biopterin metabolism are poorly understood.
• Tetrahydrobiopterin (BH4) and dihydrobiopterin (BH2) play crucial roles in vascular function.
• Aging's impact on biopterin levels and vascular beds requires elucidation.

Purpose of the Study:

• To investigate the relationship between aging, plasma and platelet biopterins (BH4 and BH2), and vascular function (cutaneous blood flow [CBF] and coronary flow reserve [CFR]).
• To assess biopterin bioavailability in different age groups of healthy adults.

Main Methods:

• Observational clinical study involving 3 age groups (18-30, 50-59, 60-70 years).
• LC-MS/MS analysis of plasma and platelet biopterins under optimized pre-analytical conditions.
• Measurement of CBF using Laser Speckle Contrast Imaging and acetylcholine-iontophoresis.
• Assessment of CFR via adenosine stress cardiac magnetic resonance.

Main Results:

• Aging significantly increased platelet BH2 and total biopterins (BH2 + BH4), and plasma BH2, without altering BH4 levels.
• Cutaneous blood flow (CBF) decreased with age and inversely correlated with platelet BH2 and total biopterins.
• Abnormal platelet BH2 levels, more prevalent in older adults, were associated with reduced CBF and CFR.

Conclusions:

• Age-related endothelial dysfunction is linked to increased circulating BH2, predominantly in platelets, without a decrease in BH4.
• Platelets are a key compartment for assessing biopterin bioavailability and its impact on vascular function.
• Peripheral vascular function declines with age in healthy individuals, highlighting biopterins as potential therapeutic targets.