# Specialized pro-resolving mediators (SPMs)

Specialized pro-resolving mediators (SPMs) are your body's 'stop' signals for inflammation. They are bioactive fats made from polyunsaturated fatty acids. Lipoxins come from arachidonic acid (an omega-6), while resolvins, protectins, and maresins are built from the omega-3s EPA and DHA as inflammation winds down. SPMs do not just passively let inflammation fade; they actively end it. They tell immune cells (macrophages) to clear out dead cells (efferocytosis), hold back incoming neutrophils, boost germ-killing, and help tissue heal. Charles Serhan established this in his 2014 Nature review, defining resolution as an active, built process. Two SPMs, Resolvin D1 (RvD1) and Maresin-1 (MaR1), can be measured in your blood (by LC-MS/MS), and they fall with age as pro-inflammatory signals rise. That shift feeds 'inflammaging': aged tissues show a high ratio of inflammatory leukotrienes to resolvins and poor dead-cell clearance, which lets senescent cells pile up. In aging mice, RvD1 restores that clearance by protecting a receptor (MerTK) on macrophages (Rymut et al. 2020). In humans, the omega-3 trial evidence is still mostly mechanistic, and no SPM-based drug is approved yet.

## Sources

- Serhan CN. (2014). Pro-resolving lipid mediators are leads for resolution physiology. Nature. https://doi.org/10.1038/nature13479
- Serhan CN, Levy BD. (2018). Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. Journal of Clinical Investigation. https://doi.org/10.1172/JCI97943
- Rymut N, Heinz J, Sadhu S, Hosseini Z, Riley CO, Marinello M, Maloney J, MacNamara KC, Spite M, Fredman G. (2020). Resolvin D1 promotes efferocytosis in aging by limiting senescent cell-induced MerTK cleavage. FASEB Journal. https://doi.org/10.1096/fj.201902126R

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_Canonical: https://longevity-switzerland.com/en/glossary/specialized-pro-resolving-mediators · Part of Longevity Cities · Updated 2026-06-22_