title: Aging delays resolution of acute inflammation in mice: reprogramming the host response with novel nano-proresolving medicines.
abstract: Aging is associated with an overt inflammatory phenotype and physiological decline. Specialized proresolving lipid mediators (SPMs) are endogenous autacoids that actively promote resolution of inflammation. In this study, we investigated resolution of acute inflammation in aging and the roles of SPMs. Using a self-resolving peritonitis and resolution indices coupled with lipid mediator metabololipidomics, we found that aged mice had both delayed resolution and reduced SPMs. The SPM precursor docosahexaenoic acid accelerated resolution via increased SPMs and promoted human monocyte reprogramming. In aged mice, novel nano-proresolving medicines carrying aspirin-triggered resolvins D1 and D3 reduced inflammation by promoting efferocytosis. These findings provide evidence for age-dependent resolution pathways in acute inflammation and novel means to activate resolution.
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
authors.forename: Hildur H
authors.initials: HH
authors.lastname: Arnardottir
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
authors.forename: Romain A
authors.initials: RA
authors.lastname: Colas
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115 cnserhan@zeus.bwh.harvard.edu.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D012898:Autacoids / Q000276:immunology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D008297:Male; D055432:Metabolomics; D051379:Mice; D008807:Mice, Inbred BALB C; D050997:Nanomedicine; D010538:Peritonitis / Q000276:immunology*; D025341:Principal Component Analysis; D015054:Zymosan / Q000276:immunology
chemical_list: D012898:Autacoids; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; C518399:resolvin D1; C583088:resolvin D3; D004281:Docosahexaenoic Acids; D015054:Zymosan; D015118:Eicosapentaenoic Acid; D001241:Aspirin