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0Researchers developed innovative bioorthogonal tools to monitor the life cycle of proteins within specific brain cells of living mice. Their study reveals that neuronal protein degradation slows significantly with age, with the average protein lifespan doubling in older subjects. This decline in maintenance leads to the formation of an aged neuronal "aggregome," a collection of over 1,700 proteins that fail to break down and instead form clumps. Many of these accumulating proteins are linked to synaptic function and neurodegenerative risk genes, suggesting a direct connection to cognitive decline. Additionally, the study found that microglia increasingly collect these slow-degrading synaptic proteins as the brain ages. These findings highlight how a breakdown in cellular waste management contributes to the progression of age-related brain diseases.
References:
Guldner I H, Wagner V P, Moran-Losada P, et al. Ageing promotes microglial accumulation of slow-degrading synaptic proteins[J]. Nature, 2026: 1-12.
