An Aging Clock from Aqueous Humor
Our biochemistry changes with age in ways that are broadly similar from person to person, occurring due to the same underlying mechanisms of aging. Any sufficiently large set of biological data can in principle be used to find an aging clock, some combination of weighted measures that assesses biological age or chronological age. As an illustration of that point, researchers here use the contents of aqueous humor from the eye to do just that. This approach is unlikely to be widely used, given that clocks based on blood samples or other more easily accessible data work just as well when it comes to determining biological age, but researchers note the possibility of assessing risk or progression of neurodegenerative conditions based on this approach.
To map protein production by different types of cells within the eye, researchers used a high-resolution method to characterize proteins in 120 liquid biopsies taken from the aqueous or vitreous humor of patients undergoing eye surgery. Altogether, they identified 5,953 proteins and were able to trace each protein back to specific cell types.
To investigate the relationship between disease and molecular aging, the researchers built a machine learning model that can predict the molecular age of the eye based on a subset of 26 proteins. The model was able to accurately predict the age of healthy eyes but showed that diseases were associated with significant molecular aging. For diabetic retinopathy, the degree of aging increased with disease progression and this aging was accelerated by as much as 30 years for individuals with severe (proliferative) diabetic retinopathy. These signs of aging were sometimes observable before the patient displayed clinical symptoms of the underlying disease and lingered in patients who had been successfully treated.
The researchers also detected several proteins that are associated with Parkinson's disease. These proteins are usually identified postmortem and current diagnostic methods aren't capable of testing for them, which is one reason Parkinson's diagnoses are so difficult. Screening for these markers in eye fluid could enable earlier diagnosis of Parkinson's disease and later therapeutic monitoring.