Linking lysosomal aging with lysosomal storage disorders

The researchers mapped the metabolic shifts that lysosomes undergo during the normal aging process. 

By utilizing rapid organelle purification methods (like LysoIP), the authors discovered that as mammals age normally, their lysosomes accumulate a distinct cocktail of toxic metabolites that heavily mirrors the pathology of fatal, juvenile lysosomal storage disorders (LSDs).

The study demonstrated that aged lysosomes across multiple tissues (specifically the brain, heart, skeletal muscle, and white adipose tissue) progressively accumulate two primary classes of metabolites:

Glycerophosphodiesters (GPDs): The chronic accumulation of GPDs within aging lysosomes directly mirrors the metabolic hallmark of Batten disease (a devastating juvenile neurodegenerative LSD).

Cystine: The dramatic buildup of this amino acid derivative mimics the cellular pathology of cystinosis.

The researchers also found increased levels of these structural lipids in aged lysosomes, closely tracking the profiles seen in Gaucher disease and Niemann-Pick disease.

https://www.science.org/doi/10.1126/science.ady0832