Lysosomal multi-omics reveals altered sphingolipid catabolism associated with lysosomal dysfunction in the aging brain.

Lysosomal lipid and protein changes in the aging brain show increased myelin components and disrupted sphingolipid breakdown, especially in microglia, indicating dysfunction.

• Why it matters: Understanding lipid alterations in lysosomes during aging is crucial because they impact brain health and may contribute to neurodegenerative diseases, yet their specific roles are unclear.
• What they did: Using mass spectrometry and multi-omics analysis on murine cortical lysosomes from 3 to 24 months, the study identified age-related shifts in lipid and protein composition, highlighting altered sphingolipid metabolism.
• The result: Findings reveal that aging causes lysosomal enlargement and dysfunction linked to accumulation of myelin-derived glycosphingolipids, resembling lysosomal storage diseases and emphasizing the importance of organelle-specific lipid analysis.