A collaborative study published in eLife assessed the possibility of using fundus retinal imaging as markers and predictors for chronological age.
Give me some background.
While other predictive aging clocks exist—such as phenotypic age and epigenetic clocks—many require invasive sample collection. Unfortunately, these clocks have limited accuracy in short-time scales.
Previous research has shown that the microvasculature in the retina could be a reliable indicator of the overall health of the brain and the body’s circulatory system. Many changes in the vascular system first appear in the smallest blood vessels, and retinal capillaries are some of the smallest in the body.
Talk about the study.
In collaboration with Google Research, which previously developed deep-learning models to detect diabetic retinopathy, investigators designed a retinal aging clock called eyeAge.
This model was trained on the EyePACS—a U.S.-based medical screening service—dataset and then applied to the EyePACS and UK Biobank cohorts, which cumulatively involve more than 164,000 patients.
What else?
Researchers from the Buck Institute for Research on Aging led a genome-wide analysis (GWAS) of the UK Biobank cohort to reinforce the individual-specific nature of eyeAge.
To validate these results, a knockdown technique (which temporarily stops or decreases the expression of a target gene) was performed on Alk, a Drosophila homolog of the top locus from the GWAS.
Findings?
The model showed a strong correlation between chronological age and eyeAge, with a mean absolute error (MAE) of 2.86 and 3.30 years on quality-filtered data from EyePACS and UK Biobank, respectively.
Investigators also found that eyeAge was independent of blood marker-based measures of biological age, maintaining an all-cause mortality hazard ratio of 1.026, even when adjusted for phenotypic age.
Lastly, by knocking down the gene ALKAL2, which enables tyrosine kinase activity, age-related vision loss slowed down and extended the lifespan of flies.
Significance?
Because fundus imaging is non-invasive and cost efficient, eyeAge provides an opportunity for “longitudinal patient analysis to assess the rate of aging,” the study authors concluded.
Additionally, the study outlines the potential for using a retinal aging clock to study age-related disease and “quantitatively measure aging on very short time scales, allowing for quick and actionable evaluation of gero-protective therapeutics.”
Expert thoughts?
According to Pankaj Kapahi, PhD, co-author of the study: "This is human data that provides targets for potential treatments for age-related diseases. The fact that we might be able to track their efficacy in such a low cost, non-invasive way is a huge plus."