Organelle Aging Predicts Human Disease

Premature aging of four or more organelle compartments in plasma and cerebrospinal fluid proteomes is linked to up to 22-fold higher kidney disease risk and up to 8-fold mortality risk.

• Why it matters: It is unknown whether subcellular organelle aging can predict human disease, despite evidence that organelles age differently across the lifespan.
• What they did: The study modeled aging of 10 organelles using organelle-enriched proteins from plasma and cerebrospinal fluid proteomes in 61,931 individuals, estimating accelerated compartments and organelle aging signatures.
• The result: Disease groups show distinct organelle aging signatures, with risk increasing as the number of accelerated organelles rises; APOE-ε4 dosage is associated with lysosomal and mitochondrial aging and reduced PDP1 levels.

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