Algae-derived omega-3 supplementation containing 1,397 mg DHA and 749 mg EPA selectively reduced prostaglandin E2 (PGE2) levels in 69-year-old adults over 8 weeks, independent of exercise effects. This inflammatory lipid mediator decrease correlated significantly with reduced C-reactive protein levels. This targeted reduction of PGE2 represents a mechanistically precise anti-inflammatory effect that could prove valuable for healthy aging strategies. PGE2 drives multiple inflammatory cascades associated with age-related decline, including joint inflammation, immune dysfunction, and tissue repair impairment. The algae-sourced formulation offers a sustainable alternative to fish oil while delivering therapeutic omega-3 ratios. However, the study's modest 40-person cohort and 8-week duration limit broader conclusions about long-term inflammatory control. Surprisingly, the pro-resolution mediator resolvin E1 declined despite supplementation, suggesting complex metabolic interactions in older adults. The selective PGE2 targeting, rather than broad-spectrum lipid mediator changes, indicates omega-3s may work through specific enzymatic pathways rather than general membrane incorporation. This mechanistic specificity could guide more targeted anti-aging interventions, though larger trials are needed to establish clinical significance for age-related inflammatory conditions.