期刊
JOURNAL OF PROTEOME RESEARCH
卷 12, 期 6, 页码 2679-2689出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr400064a
关键词
membrane unsaturation; phospholipids oxidation; rate of aging; mitochondria; free radicals; phase-II antioxidants
资金
- Spanish Ministry of Science and Innovation [BFU2009-11879/BFI]
- Autonomous Government of Catalunya [2009SGR735]
- Spanish Ministry of Health [PI081843, PI111532]
- COST Action B35
- Autonomous Government of Catalonia
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 the brain and spinal cord but not in the 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 signaling 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 the 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.
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