Specialized pro-resolving mediators (SPMs)

Specialized pro-resolving mediators (SPMs) are endogenous bioactive lipids from polyunsaturated fatty acids: lipoxins arise from arachidonic acid (omega-6), while resolvins, protectins (neuroprotectins), and maresins are enzymatically synthesized from EPA and DHA (omega-3) during resolution of acute inflammation. SPMs actively terminate inflammation: they stimulate macrophage efferocytosis (clearance of apoptotic cells), limit neutrophil recruitment, enhance microbial killing, and promote tissue repair — a distinction Charles Serhan established in his 2014 Nature review defining resolution as a biosynthetically driven process. Resolvin D1 (RvD1) and maresin-1 (MaR1) are measurable in human plasma via liquid chromatography-tandem mass spectrometry (LC-MS/MS) and decline with age as pro-inflammatory eicosanoids rise. Impaired SPM biosynthesis contributes to inflammaging: aged tissues show elevated leukotriene-to-resolvin ratios and defective efferocytosis, accelerating senescent-cell accumulation. In murine aging models, RvD1 rescues efferocytosis defects by preventing MerTK cleavage on macrophages (Rymut et al. 2020). Human evidence from omega-3 supplementation trials remains largely mechanistic; no SPM-based therapeutic has received regulatory approval.