NOVATO, Calif. — Many believe the eyes are the window to the soul, but Buck Institute professor Pankaj Kapahi believes they’re a window to aging. His lab has successfully shown how imaging of the fundus (the blood vessel-rich tissue found in the retina) can help doctors track human aging. This method is non-invasive, less expensive, and more accurate than other aging clocks currently available.
The research team also performed a genome-wide association study (GWAS) to establish the genetic basis for this “clock,” which they call eyeAge. Study authors conducted this project in collaboration with Google Health and Zuckerberg San Francisco General Hospital.
“This type of imaging could be really valuable in tracking the efficacy of interventions aimed at slowing the aging process,” says Kapahi, a senior co-author of the study, in a media release. “The results suggest that potentially, in less than one year we should be able to determine the trajectory of aging with 71% accuracy by noting discernable changes in the eyes of those being treated, providing an actionable evaluation of gero-protective therapeutics.”
Prof. Kapahi notes that retinal scans are likely more reliable due to changes in the eye being less susceptible to day-to-day fluctuations in comparison to other common biomarkers from the blood that are more dynamic. Something as simple as eating a meal or a mild infection can influence these other biomarkers.
Examining the eyes is a great way to find disease
Meanwhile, a growing body of evidence indicates that the microvasculature in the retina may be a reliable indicator of the overall health of the body’s circulatory system and brain. After all, changes in the eye accompany aging and various age-related diseases including age-related macular degeneration (AMD), diabetic retinopathy, Parkinson’s, and Alzheimer’s disease.
Ophthalmologists routinely identify the early symptoms of AIDS, chronic high blood pressure, and tumors in the eyes. While this may sound shocking to some, researchers explain that any subtle changes in the vascular system first appear in the smallest blood vessels – and capillaries in the retina are among the smallest in the body.
Still, subtle changes in these small blood vessels often go undetected by even the most sophisticated modern instruments, making it necessary to use deep learning – an effort spearheaded by Google Research. The team from Google (and elsewhere) put together a series of models for predicting diabetic retinopathy from retinal images. Researchers have since gone on to use retinal images to identify at least 39 eye diseases such as glaucoma, diabetic retinopathy, and AMD, as well as non-eye diseases including chronic kidney disease and cardiovascular disease.
In all, Google researchers trained and tuned the model for eyeAge using the well-studied EyePACS data set that involved over 100,000 patients, and then applied it to more than 64,000 patients from the UK Biobank.
“Our study emphasizes the value of longitudinal data for analyzing accurate aging trajectories. Through EyePACS longitudinal dataset involving multiple scans from individual people over time our results show a more accurate positive prediction ratio for two consecutive visits of individual rather than random, time-matched individuals,” explains Sara Ahadi, co-corresponding author and a former Fellow at Google Research, who is now Senior Computational Biologist at Alkahest.
Ahadi also notes that eyeAge is independent from phenotypic age (a well-established aging clock based on blood markers).
“We are looking at aging through a different lens and bringing more information to the table. We hope eyeAge will be utilized along with other clocks to make tracking aging more robust, powerful and comprehensive.”
Researchers performed the genome study at the Buck Institute using biological samples provided by the UK Biobank. Kenneth Wilson, a postdoc at the Buck Institute, validated some of the genes highlighted in this analysis, building on previous Buck research that uncovered a connection between diet, eye health, and lifespan in Drosophila (fruit flies).
At the time, Wilson identified nearly 30 genes in patient samples associated with visual decline, diabetes, hearing loss, Alzheimer’s disease, cardiovascular disease, and stroke. One of the genes in particular, ALKAL2, has been shown to extend lifespan in Drosophila (via the fly homolog ALK). When Wilson knocked down the gene in the flies, their vision improved later in life and their lifespans increased.
All in all, Prof. Kapahi says the results from this research set the stage nicely for follow-up studies.
“It would be really informative to understand how these genes, which are already linked to other age-related diseases, are affecting the changes we are seeing in the eye,” he concludes. “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.”
The study is published in the journal eLife.