PUFA Therapy May Reverse Vision Loss in Aging Mice

A new study led by researchers at UC Irvine, in collaboration with the Polish Academy of Sciences and the Health and Medical University in Potsdam, reveals that polyunsaturated fatty acid (PUFA) supplementation may reverse age-related visual decline in mice. Published in Science Translational Medicine, the study builds on previous research identifying ELOVL2 as a critical gene involved in visual aging and proposes a new therapeutic approach that bypasses direct gene activation.

Revisiting ELOVL2: A Key Gene in Visual Aging

The study expands on earlier work investigating the role of Elongation of Very Long Chain Fatty Acids Protein 2 (ELOVL2), an enzyme recognized as a biomarker of aging and crucial for synthesizing very-long-chain polyunsaturated fatty acids (VLC-PUFAs) and docosahexaenoic acid (DHA). In prior studies, boosting ELOVL2 gene expression in aging mice increased retinal DHA levels and improved visual function.

However, the new research aimed to identify a therapeutic path that bypasses ELOVL2 activation, focusing instead on direct supplementation with specific lipids.

PUFA Injections Improve Vision in Aged Mice

The research team found that injecting aged mice with a particular polyunsaturated fatty acid led to improved visual function, suggesting a proof-of-concept for lipid-based therapy targeting visual aging. Importantly, the same effect was not observed with DHA alone, a commonly studied omega-3 fatty acid.

“Our work really confirms the fact that DHA alone cannot do the work,” said Dorota Skowronska-Krawczyk, PhD, Associate Professor of Ophthalmology and Physiology & Biophysics at UC Irvine. “But we have this other fatty acid that is seemingly working and improving vision in aged animals.”

The study also showed that PUFA injections reversed molecular markers of aging in the retina, offering insight into the mechanisms of action and therapeutic potential.

Genetic Link Between ELOVL2 and AMD Progression

In addition to demonstrating a functional benefit in animal models, the researchers identified genetic variants in the ELOVL2 enzyme associated with faster progression of age-related macular degeneration (AMD). This genetic link strengthens the case for ELOVL2 as both a therapeutic target and a predictive biomarker for AMD risk.

“Now we actually have a genetic connection to the disease and its aging aspect,” said Skowronska-Krawczyk, “so we could potentially identify people at higher risk for vision loss progression.”

Beyond Vision: Implications for Immune Aging and Systemic Health

In collaboration with UC San Diego, the team has begun investigating the role of lipid metabolism in immune system aging. Early findings suggest that loss of ELOVL2 function accelerates immune cell aging, raising the possibility that systemic lipid supplementation could provide broader anti-aging benefits, including potential roles in blood cancer biology.

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

Reference:

Fangyuan Gao et al, Retinal polyunsaturated fatty acid supplementation reverses aging-related vision decline in mice, Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.ads5769