Accelerated Epigenetic Aging is Associated with Faster Glaucoma Progression: A DNA Methylation Study

Area of Science:

• Ophthalmology
• Epigenetics
• Aging Research

Background:

• Glaucoma is a leading cause of irreversible blindness.
• Understanding factors influencing glaucoma progression is crucial for patient management.
• Epigenetic age, reflecting biological aging, is a novel area of research with potential implications for age-related diseases.

Purpose of the Study:

• To investigate the association between epigenetic age acceleration and the rate of glaucoma progression.
• To determine if epigenetic age can serve as a prognostic biomarker for glaucoma.

Main Methods:

• Retrospective cohort study of 200 primary open-angle glaucoma (POAG) patients (100 fast progressors, 100 slow progressors).
• Epigenetic age calculated using Horvath, Hannum, PhenoAge, and GrimAge clocks from DNA methylation profiles.
• Age acceleration (AgeAccel) defined as residual of epigenetic age on chronological age.
• Multivariable logistic regression used to assess the association between AgeAccel and fast glaucoma progression.

Main Results:

• Fast glaucoma progressors exhibited significantly greater age acceleration compared to slow progressors using Horvath and Hannum clocks.
• Each year of Horvath AgeAccel was associated with a 15% increased odds of fast glaucoma progression (OR 1.15, P<0.001), after adjusting for confounders.
• Hannum and GrimAge clocks also showed significant associations with fast progression; association was stronger with lower intraocular pressure.

Conclusions:

• Accelerated epigenetic aging is significantly associated with faster glaucoma progression.
• These findings suggest that biological age, as indicated by DNA methylation patterns, may influence optic nerve susceptibility to damage.
• Epigenetic age acceleration emerges as a potential prognostic biomarker for glaucoma progression.