Membrane lipid composition is an important correlate of the rate of aging of animals. Dietary methionine restriction (MetR) increases lifespan in rodents. The underlying mechanisms have not been elucidated but could include changes in tissue lipidomes. In this work we demonstrate that 80% MetR in mice induces marked changes in the brain, spinal cord and liver lipidomes. Further, at least 50% of the lipids changed are common in brain and spinal cord, but not in liver; suggesting a nervous system-specific lipidomic profile of MetR. The differentially expressed lipids includes a) specific phospholipid species, which could reflect adaptive membrane responses; b) sphingolipids, which could lead to changes in ceramide signalling pathways, and c) the physiologically redox-relevant ubiquinone 9, indicating adaptations in phase II antioxidant response metabolism. In addition, specific oxidation products derived from cholesterol, phosphatidylcholine and phosphatidylethanolamine were significantly decreased in brain, spinal cord and liver from MetR mice. These results demonstrate the importance of adaptive responses of membrane lipids leading to increased stress resistance as a major mechanistic contributor to the lowered rate of aging in MetR mice.