Aging mouse brains accumulate myelin lipids that drive lysosomal dysfunction
Lysosomal multi-omics shows altered sphingolipid breakdown leads to glycosphingolipid buildup and lysosome enlargement, especially in aging microglia.
Cell reports · Sarkar C et al. · Paper published 1 Oct 2026
In mice aged 3 to 24 months, researchers tracked longitudinal changes in the lipidome and proteome of lysosomal fractions from the cerebral cortex. The team used mass spectrometry alongside multi-omics factor analysis to uncover drivers of lysosomal aging. The analysis revealed an age-dependent increase in both lipid and protein myelin components within lysosomes. This change pointed to altered sphingolipid catabolism that favors the breakdown of sphingomyelins over glycosphingolipids. Experimental validation confirmed that the age-dependent accumulation of myelin-derived glycosphingolipids associates with lysosomal enlargement and dysfunction. These cellular defects were most pronounced in microglia, exhibiting lipid changes that mirror those seen in lysosomal storage diseases.
Why it matters
The findings link impaired lipid degradation directly to organelle decline in brain aging. They demonstrate that aged microglia display clearance failures similar to lysosomal storage disorders.
Caveats
The study was conducted exclusively in mouse cortical tissue, and the abstract provides no evidence confirming whether identical lipid changes happen during human brain aging.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
Lysosomal multi-omics reveals altered sphingolipid catabolism associated with lysosomal dysfunction in the aging brain
Sarkar C, Chen Y, Nguyen DP et al.
Cell reports · 1 Oct 2026 · Peer-reviewed
- Relevance
- Core geroscience
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- Important
- Evidence
- Animals
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