Age-related macular degeneration affects one million Italians. It is the leading cause of blindness in Western countries after age 55. Until now, it was thought to be irreversible. Researchers at theUC Irvine they proved the opposite: by injecting fatty acids very long-chain polyunsaturated fatty acids (VLC-PUFA) In older mice, their vision improved significantly. We're not talking about slowing the decline, but actually reversing it.
The secret is to bypass the enzyme ELOVL2, which loses efficiency with aging. The study, published in Science Translational Medicine, opens up concrete scenarios for a preventive and curative therapy for age-related sight loss.
The enzyme that betrays us over time
THEELOVL2 It's a well-established biomarker of aging. An enzyme that produces very long-chain fatty acids, essential for retinal health. With age, its activity slows. The result is predictable: fewer VLC-PUFAs, less DHA in the retina, and worsening vision. As already demonstrated in other research, DHA (docosahexaenoic acid) is essential for brain function, vision and the regulation of inflammatory phenomena. But that alone is not enough.
Dorota Skowronska-Krawczyk, associate professor in the Departments of Physiology and Biophysics and Ophthalmology of theUC Irvine, has explained:
“We have shown that we have worse vision when this ELOVL2 enzyme is not active.”
In a previous study, boosting ELOVL2 gene expression in older mice increased DHA levels in the eye and improved vision. The new research sought a way to achieve the same benefits without relying on the enzyme.
Bypassing the biological clock with fatty acids?
With aging, changes in lipid metabolism lead to a decline in very-long-chain polyunsaturated fatty acids in the retina. This decline impairs vision and contributes to macular degeneration. The ELOVL2 gene plays a crucial role in the production of both VLC-PUFAs and DHA. When researchers injected elderly mice with a specific polyunsaturated fatty acid, their visual performance improved.
“It’s a proof of concept for turning lipid injection into a potential therapy,” Skowronska-Krawczyk says.
"What's important is that we didn't see the same effect with DHA. Others have also questioned DHA's ability to slow the progression of age-related macular degeneration.
Our work really confirms the fact that DHA alone can't do the job, but we have this other fatty acid that apparently works and improves vision in older animals.
We also demonstrated at the molecular level that it actually reverses the hallmarks of aging.”
The genetics of fading vision
The researchers also found genetic variants in the ELOVL2 enzyme that correlate with faster progression of macular degeneration. "Now we actually have a genetic connection to the disease and its aging-related manifestations," says Skowronska-Krawczyk. "So we could potentially identify people at higher risk of progressive vision loss." This could lead not only to therapeutic treatment options, but also to targeted preventive interventions.
The discovery fits into a broader picture. In Italy, approximately 800.000-1.000.000 people show early signs of age-related macular degeneration. It is estimated that there are approximately 100.000 new cases each year, specifically approximately 15.000 new cases of neovascular macular degeneration each year.
The incidence increases with age: 1% over 50, 5% over 75, 13% over 85. Women are more affected than men.
Beyond the retina: the immune system ages too
Skowronska-Krawczyk is convinced: “I'm quite sure that it is one of the main aging genes that we should be looking at when we think about anti-aging therapies.” In collaboration with researchers from theUC San Diego, began to explore the role of lipid metabolism in the aging of the immune system.
That study found that the lack of the ELOVL2 enzyme induces accelerated aging of immune cells, suggesting that Systemic lipid supplementation could potentially counteract the effects of age on the immune system. He also suggested that lipid metabolism might play a role in blood cancers.
“Our initial study explored a potential therapy to address vision loss,” says Skowronska-Krawczyk, “but with the information we’ve learned about immune aging, we’re confident that supplementation therapy will also boost the immune system.”
Fatty acids, sometimes the solution is to get around the problem
The study involved researchers from theManchester University and Health and Medical University Potsdam, in Germany. The team used older mice to test whether directly administering VLC-PUFA fatty acids could improve visual function without reactivating the ELOVL2 enzyme. The results were clear: vision improved. At the molecular level, the signs of aging have been reversed.
This approach represents a paradigm shift. It's no longer about trying to "repair" the enzyme or slow its decline. It's about directly providing the body with what it needs. It's like a colleague struggling to work: instead of asking him to do more, you give him the finished work. It works.
The research is now focused on translating these findings to humans. Injections of VLC-PUFA fatty acids could become a preventative therapy for those with risky genetic variants, or a treatment for those who have already developed the first signs of macular degeneration.
As the ELOVL2 enzyme continues to be studied as a major biomarker of aging, the path to targeted lipid therapies becomes increasingly concrete.
Fading eyesight with age may no longer be an inevitable fate. You just need to know what fat to apply, and when.
