Recent research has uncovered evidence of cellular senescence in neurons within the aging brain. Despite being post-mitotic cells, neurons can still become senescent, particularly in response to damage or toxicity. In the context of neurodegenerative diseases, more neurons are found to re-enter the cell cycle, leading to senescence. This discovery adds support to the potential use of senolytic drugs in treating neurodegenerative conditions.
Moreover, a study using bioinformatics analysis of single-nucleus transcriptome datasets has identified rare cell populations in the brain that exhibit cell cycle-related events, primarily in excitatory neurons. These cells are prone to cellular senescence, with their numbers increasing in late-onset Alzheimer’s disease and other conditions like Parkinson’s disease-Lewy body dementia. Transcriptomic profiling revealed disease-specific differences in these neurons, indicating increased inflammation and metabolic disruption in affected brains.
Further validation in a mouse model of brain aging confirmed the relationship between the cell cycle and senescence processes in neurons. This research highlights the potential importance of targeting senescent neurons in neurodegenerative diseases. The full study can be accessed at: https://doi.org/10.1371/journal.pbio.3002559.
