Aging mouse brains show opposing shifts in two cell signals
Experiments in genetically modified mice linked brain aging to greater activity of an inflammation-regulating pathway and reduced activity of another.
Our read
Mechanisms- Studied:
- Experiments in genetically modified mice
- What changed:
- Aging mouse brains had greater NF-κB activity and lower Notch activity
- The catch:
- Effects of Notch activation on age-related brain inflammation were not measured in animals
- Why it’s aging research:
- It studies something that builds up in the body with age.
Editor of record: Boris Djordjevic · AgingResearch.News
In genetically modified mice, animal experiments linked brain aging to increased activity of NF-κB, a regulator of inflammatory genes, and reduced activity of Notch, a cell-signaling pathway. In young mice, activating NF-κB in astrocytes, cells that support nerve cells, mimicked early formation of inflammatory secretions associated with senescence, a state in which cells stop dividing. It also suppressed Notch signaling.
Analyses identified sites within genes for these secretions occupied by gene-regulating proteins from both pathways, allowing combined control. The authors also found physical interactions through which activated Notch could dampen NF-κB signaling. In a separate experiment with astrocytes grown in the lab, activating Notch with a drug reduced NF-κB-driven activity of genes for the inflammatory secretions.
Why it matters
Inflammatory secretions from senescent brain cells are linked to higher risk of neurodegenerative disorders in humans. The authors identified the interaction between these pathways as a potential target for reducing age-related brain inflammation.
Caveats
The drug experiment measured gene activity in lab-grown astrocytes, not whether activating Notch reduced age-related brain inflammation in animals or people.
The paper
Notch/NF-κB crosstalk signaling controls SASP gene expression during brain aging
University Hospital Ulm; University of Ulm
Nucleic Acids Research, Nov 5, 2026, CC BY
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