Clocking POAG Progression

A recent study published in medRxiv has revealed a significant link between accelerated epigenetic aging and the speed of progression in primary open-angle glaucoma (POAG). Conducted by researchers from the Bascom Palmer Eye Institute, University of Miami, and Duke Eye Center, Duke University, the study utilized epigenetic clocks to assess the biological age of 200 POAG patients – 100 with fast glaucoma progression and 100 with slow progression.

Epigenetic clocks, like the widely recognized Horvath and Hannum clocks, estimate biological age by examining DNA methylation patterns – chemical modifications in DNA that are cell and tissue specific – at specific sites of the body. In this particular study, epigenetic age acceleration was calculated as the residual difference between an individual’s chronological and biological age based on these clocks. Positive values indicate that a person’s biological age is higher than their chronological age, suggesting faster biological aging.

The results from the study demonstrated that fast-progressing POAG patients had significantly greater biological age acceleration than those with slower disease progression. The Horvath clock showed the strongest association between the two variables: on average fast progressors had an epigenetic age almost three years greater than slow progressors. Further analysis revealed that, for each additional year of accelerated biological age according to the Horvath clock, the likelihood of fast glaucoma progression increased by 15 percent, even after adjusting for other factors like intraocular pressure (IOP), central corneal thickness, and baseline disease severity.

The study underscores the potential for accelerated epigenetic aging – as reflected by DNA methylation – being used as a prognostic biomarker for glaucoma progression, especially in cases where other risk factors, such as IOP, are well-managed. Interestingly, the association between age acceleration and rapid glaucoma progression was even stronger in patients with relatively low IOP levels, suggesting that biological aging may independently increase optic nerve susceptibility to damage. These findings are consistent with prior research linking accelerated biological aging to vulnerability in neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

The study authors conclude that this observed association between biological aging and glaucoma progression could lead to innovative neuroprotective strategies targeting age-related mechanisms. Compounds like nicotinamide mononucleotide (NMN), which has shown neuroprotective potential in animal studies, could help to slow glaucoma progression by supporting cellular resilience against age-related stressors. However, the authors note that further studies are now needed to validate these findings and explore the therapeutic possibilities of slowing biological aging to mitigate glaucoma’s progression.