Reversing age-related vision decline

(Press-News.org) Changes in vision are often a common sign of aging. If you sit in a dimly lit restaurant with anyone over the age of 60, you’ll likely hear the person say, “Hold on — let me pull out my cell phone. I need more light to read the menu!” But what if we could reverse age-related visual decline?

In a new study, UC Irvine researchers explore a possible therapy for addressing “aging” in the eye and for preventing diseases such as age-related macular degeneration (AMD).

“We show the potential for reversing age-related vision loss,” says Dorota Skowronska-Krawczyk, PhD, an associate professor in the Department of Physiology and Biophysics and the Department of Ophthalmology and Visual Sciences. The study was a collaboration between researchers from UC Irvine, the Polish Academy of Sciences, and the Health and Medical University in Potsdam, Germany.

They outline their findings in “Retinal polyunsaturated fatty acid supplementation reverses aging-related vision decline in mice,” a paper published in Science Translational Medicine.

Understanding the “Aging” Gene
The work is a follow-up to an earlier study on Elongation of Very Long Chain Fatty Acids Protein 2 (ELOVL2), an established biomarker of age. “We showed that we have lower vision when this ELOVL2 enzyme isn’t active,” says Skowronska-Krawczyk, also a faculty member in the Robert M. Brunson Center for Translational Vision Research at the UC Irvine School of Medicine. In that work, the researchers found that enhancing ELOVL2 gene expression in aging mice boosted levels of the omega−3 fatty acid docosahexaenoic acid (DHA) in the eye and improved vision.

The more recent study sought to identify a way to bypass the need for the ELOVL2 enzyme.

As we age, changes in lipid metabolism lead to a decline in very-long-chain polyunsaturated fatty acids (VLC-PUFAs) in the retina, which in turn affects our vision and can lead to AMD. The ELOVL2 gene is a key enzyme in the production of VLC-PUFAs as well as DHA.

Injecting aged mice with the polyunsaturated fatty acid improved visual function. “It’s a proof-of-concept for turning lipid injection into a possible therapy,” says Skowronska-Krawczyk. “What is important is that we didn’t see the same effect with DHA.” Others have also questioned the ability of DHA to slow AMD progression.

“Our work really confirms the fact that DHA alone cannot do the work, but we have this other fatty acid that is seemingly working and improving vision in aged animals,” says Skowronska-Krawczyk. “We have also shown on a molecular level that it actually reverses the aging features.”

Furthermore, the researchers found genetic variants in the ELOVL2 enzyme that correlate with faster progression of AMD. “Now we actually have a genetic connection to the disease and its aging aspect,” says Skowronska-Krawczyk, “so we could potentially identify people at higher risk for vision loss progression.” This could lead to not only therapeutic treatment options but also targeted interventions for prevention.

These findings have only further solidified Skowronska-Krawczyk’s view of the importance of the ELOVL2 enzyme. “I am pretty convinced it’s one of the top aging genes that we should look at when we think about anti-aging therapies.”

Looking Beyond the Retina
In a collaboration with researchers from UC San Diego, Skowronska-Krawczyk has also started to explore the role of lipid metabolism in immune system aging. That study found that the lack of ELOVL2 enzyme induces accelerated aging of immune cells, suggesting that systemic lipid supplementation could potentially counteract the effects of age on the immune system. It also suggested that lipid metabolism might play a role in blood cancers.

“Our first study explored a potential therapy to address vision loss,” says Skowronska-Krawczyk, “but with the information we’ve since learned about immune aging, we are hopeful the supplementation therapy will boost the immune system as well.”

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