Specific Lipidome Signatures in Central Nervous System from Methionine-Restricted Mice

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.