Lipidomic profiling reveals age-dependent changes in plasma membrane lipids that affect neural stem cell aging

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• The aging brain experiences reduced neural stem cell (NSC) regenerative capacity.
• The specific role of complex lipids in NSC aging is not well understood.

Purpose of the Study:

• To investigate age-related changes in complex lipids within quiescent neural stem cells.
• To determine the functional impact of these lipid alterations on NSC activation and regenerative potential.

Main Methods:

• Lipidomic profiling (mass spectrometry) and spatial lipidomics were used to analyze lipid changes in NSCs in vitro and in vivo.
• Plasma membrane vesicles were isolated for detailed lipid composition analysis.
• Genetic manipulation (MBOAT2 knockout and overexpression) and lipid supplementation studies were conducted.

Main Results:

• Significant age-related changes in complex lipids, including increased polyunsaturated fatty acids, were identified in quiescent NSCs.
• Aging decreased plasma membrane order, a critical biophysical property.
• MBOAT2 deficiency worsened lipid changes and impaired NSC activation, while MBOAT2 overexpression and lipid supplementation from young NSCs restored NSC activation.

Conclusions:

• Age-related alterations in plasma membrane lipids, particularly affecting membrane order, impair neural stem cell function.
• Targeting MBOAT2 or supplementing specific lipids presents a potential therapeutic strategy to rejuvenate aging NSCs and counteract brain aging.