Single-nucleus analysis of aging primate intestines identifies NCoR1 decline as a conserved hallmark of intestinal aging, accompanied by barrier dysfunction, inflammation, and stem cell dysfunction. Metformin treatment restores NCoR1 levels and reverses these aging signatures, suggesting a mechanistic pathway for preserving intestinal integrity across the lifespan.
Key Points
- NCoR1 decline drives barrier dysfunction and inflammation with age
- Metformin restores NCoR1 and reverses intestinal aging signatures
- Findings conserved across primate models, translatable to humans
Longevity Analysis
Intestinal barrier integrity and epithelial regeneration are foundational to systemic health; compromise in these functions accelerates aging across multiple organs through increased microbial translocation, endotoxemia, and chronic inflammation. This work identifies NCoR1 as a specific molecular node controlling intestinal homeostasis during aging, and demonstrates that metformin—already established as a geroprotective agent—works partially through restoration of this pathway. For longevity strategies, this clarifies why intestinal health is not peripheral but central: preserving the intestinal barrier and epithelial renewal capacity directly mitigates the inflammatory load that drives age-related disease progression.
Original published by Nature Aging, by Jingyi Li.