Age-related decrease in high-density lipoproteins antioxidant activity is due to an alteration in the PON1's free...

Area of Science:

• Biochemistry
• Gerontology
• Oxidative Stress

Background:

• High-density lipoprotein (HDL) possesses antioxidant properties.
• Paraoxonase-1 (PON1) is an HDL-associated enzyme crucial for its antioxidant function.
• Aging is associated with increased oxidative stress and potential decline in antioxidant defenses.

Purpose of the Study:

• To evaluate the impact of aging on HDL antioxidant activity.
• To investigate the role of PON1 in age-related changes in HDL antioxidant capacity.
• To examine the structural and functional alterations in PON1 with aging.

Main Methods:

• Lipid peroxidation induced by hydroxyl (*OH) and superoxide (O2*-) radicals.
• Quantification of lipid peroxidation markers: conjugated dienes (CD), lipid peroxides (LP), and malondialdehyde (MDA).
• Purification and characterization of PON1 from young and elderly subjects, assessing paraoxonase (p.ase) activity, sulfhydryl (SH) group titration, and SDS-PAGE.

Main Results:

• Elderly HDL (E-HDL) exhibited significantly lower antioxidant activity (27.70%) compared to young HDL (Y-HDL) (73.08%).
• Elderly PON1 (E-PON1) showed reduced antioxidant capacity (47.08%) versus young PON1 (Y-PON1) (78.14%).
• Exposure to free radicals decreased PON1 activity and free sulfhydryl groups, particularly at cysteine-284, correlating with impaired LDL protection.

Conclusions:

• Aging diminishes the antioxidant capacity of HDL, partly due to reduced function of PON1.
• Structural modifications in PON1, specifically involving free sulfhydryl groups, contribute to its decreased antioxidant efficacy in the elderly.
• These findings highlight the vulnerability of antioxidant systems to aging and the critical role of PON1 in protecting against lipid peroxidation.