Cellular senescence in brain aging and neurodegeneration: from molecular mechanisms to translational opportunities - PubMed
2 hours ago
- #Cellular Senescence
- #Neurodegeneration
- #Brain Aging
- Cellular senescence is a key driver of brain aging and neurodegeneration, linking systemic aging to brain dysfunction.
- Senescent glial cells and 'neurescence' in neurons contribute to neuroinflammation, impaired proteostasis, and synaptic dysfunction.
- Therapeutic targets include SASP-mediated neurotoxicity and pathways like NF-κB, p38 MAPK, mTOR, and cGAS-STING.
- Senomorphic and senolytic strategies, alongside systemic interventions like plasma exchange, aim to reduce senescence burden.
- Senescence biomarkers from fluid, imaging, and multi-omics allow in vivo monitoring and stratification across disease stages.
- Central and peripheral senescence signatures partially overlap, suggesting bidirectional brain-body communication.
- Key uncertainties involve the causal role in human neurodegeneration and specificity of biomarkers.