Cellular senescence in brain aging and neurodegeneration: from molecular mechanisms to translational opportunities.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic and translational concepts without original data or systematic review
PubMed 42239645 · doi:10.3389/fncel.2026.1805691
What was done
This narrative review synthesized molecular, cellular, and translational findings regarding cellular senescence in brain aging and neurodegenerative disorders such as Alzheimer's disease. The authors evaluated mechanisms of glial senescence, neuronal senescence ("neurescence"), senescence-associated secretory phenotype pathways (NF-κB, p38 MAPK, mTOR, cGAS-STING), multi-omic and imaging biomarkers, and therapeutic approaches including senolytics, senomorphics, and therapeutic plasma exchange.
What was found
The abstract reports no quantitative metrics or statistical values. It conceptually describes how senescent glial cells and post-mitotic neurons contribute to neuroinflammation, proteostasis impairment, and synaptic dysfunction. It reports that central and peripheral senescence signatures only partially overlap, indicating bidirectional communication across the brain-body axis.
Why it matters
The review frames brain senescence as a systemic, bidirectional brain-body process rather than a cell-autonomous brain disorder, mapping out biomarker and therapeutic opportunities for neurodegeneration.
Limits
This is a narrative review with no original clinical data or systematic study selection. Direct evidence causally linking senescent cells to human brain dysfunction is currently limited, biomarker specificity remains uncertain, and criteria separating adaptive from maladaptive senescence are not established.
Cited by
- context Astrocytes are the predominant cell type in the brain to become senescent.