Background and aims: Oxylipins, including eicosanoids, are highly bioactive molecules endogenously produced from polyunsaturated fatty acids. Oxylipins play a key role in chronic disease progression. It is possible, but unknown, if oxylipin concentrations change with the consumption of functional foods or differ with subject age. Methods: Therefore, in a parallel comparator trial, 20 healthy individuals were recruited into a younger (1928 years) or older (45-64 years) age group (n = 10/group). Participants ingested one muffin/day containing 30 g of milled flaxseed (6 g alpha-linolenic acid) for 4 weeks. Plasma oxylipins were isolated through solid phase extraction, analyzed with HPLC-MS/MS targeted lipidomics, and quantified with the stable isotope dilution method. Results: At baseline, the older group exhibited 13 oxylipins >= 2-fold the concentration of the younger group. Specifically, pro-inflammatory oxylipins 5-hydroxyeicosatetraenoic acid, 9,10,13-trihydroxyoctadecenoic acid, and 9,12,13-trihydroxyoctadecenoic acid were significantly greater in the older (1.1 +/- 0.23 nM, 5.6 +/- 0.84 nM, and 4.5 +/- 0.58 nM, respectively) versus the younger group (0.34 +/- 0.12 nM, 3.5 +/- 0.33 nM, and 3.0 +/- 0.24 nM, respectively) (p < 0.05). After 4 weeks of flaxseed consumption the number of oxylipins that were >= 2-fold higher in the older versus the younger group was reduced to 3. 5-Hydroxyeicosatetraenoic acid, 9,10,13-trihydroxyoctadecenoic acid, and 9,12,13-trihydroxyoctadecenoic acid decreased in the older group to concentrations equivalent to the younger group after flaxseed consumption. Conclusion: These data suggest a potential role for oxylipins in the aging process and how nutritional interventions like flaxseed can beneficially disrupt these biological changes associated with inflammation and aging. (C) 2014 Elsevier Inc. All rights reserved.