How Omega-3s May Help Counter Age-Related Protein Damage

This review looks at advanced glycation end products (AGEs) — compounds that build up in the body over time when sugars react with proteins, fats, or DNA. As people age, AGEs accumulate more easily due to increased oxidative stress, low-grade inflammation, and reduced ability of the kidneys and enzymes to clear them out. AGEs are thought to contribute to tissue stiffening and inflammatory signaling through a receptor called RAGE.

The authors summarized existing lab, animal, and human studies exploring whether omega-3 fatty acids (EPA and DHA) can influence these AGE-related pathways. Preclinical research suggested omega-3s may reduce oxidative stress and inflammatory signaling, partly by affecting the RAGE pathway and activating a receptor called PPARγ. Some clinical studies found that omega-3 supplementation was linked to lower blood levels of AGEs, RAGE, and a related marker called pentosidine, along with increased levels of a protective receptor (AGER1).

Omega-3 intake was also associated with improvements in inflammation markers, cardiometabolic risk factors, cognitive performance, and physical function in older adults. However, the authors noted that few well-designed trials have directly measured AGE buildup in tissue (using methods like skin autofluorescence) in elderly populations, so more targeted research is needed.