Primate guts reveal ageing at the single-cell level
The small intestine ages, and that process has now been mapped in detail at the level of individual cells for the first time.
Scientists analysed the small intestine of non-human primates at single-nucleus resolution, using a technique called single-nucleus profiling. They identified what changes as the gut ages: the barrier function of the intestinal wall weakens, inflammatory activity increases, and stem cells more often adopt the wrong cell fate. The study was published in Nature Aging.
NCoR1 as a key molecule
One of the most striking findings: the protein NCoR1 declines as the gut ages. NCoR1 is a co-repressor, a molecule that regulates the activity of other genes by dampening them. When NCoR1 is lost, the way genes in intestinal cells are switched on and off changes. This appears to be associated with weakened barrier function and increased inflammation.
The researchers then tested whether metformin, a drug used for decades to treat type 2 diabetes, could reverse these changes. Metformin has attracted growing interest in recent years as a possible ageing-slowing agent. In this study, metformin treatment restored NCoR1 levels and slowed signs of intestinal ageing. These are findings from animal experiments, not human trials.
Why the gut matters for ageing
The small intestine is more than a digestive organ. It is an active barrier between the outside world and the bloodstream, and a key player in immune regulation. When that barrier deteriorates with age, substances that would normally be blocked can enter the circulation. This may contribute to the low-grade chronic inflammation, known as inflammaging, associated with ageing and age-related disease.
The finding that metformin restores NCoR1 and slows intestinal ageing is worth noting from a longevity perspective, but the authors stress that further research is needed to understand how this plays out in humans.