People say memory declines with age. But not everyone ages the same. Some keep sharp cognitive abilities past 100, while others experience memory decline starting in middle age. Recently, the scientific community has focused not only on the aging brain itself for the cause of age-related forgetfulness, but also on how the body's other organs and the brain are connected through consolidation.
An international team, including the Arc Institute in the United States, found clues outside the brain. The researchers confirmed that a specific substance produced in the gastrointestinal tract of older mice weakens the nerve signals that link the gut and the brain, reducing memory and learning ability. The findings were published in Nature on the 12th.
Evidence has steadily shown that changes occurring in other parts of the body affect the brain's memory capacity. Several studies have reported that the gut microbiota (a community of bacteria living in the gut) influences learning, memory, and behavior. However, it has not been clearly identified through which specific pathways this consolidation operates.
To determine whether changes in the gut microbiota affect cognitive decline, the researchers exposed young mice to the microbiota of older mice. As a result, the gut environment of the young mice shifted in the same direction as that of the older mice, and their scores in memory and cognitive tests dropped noticeably. Both the ability to remember new objects and to escape a maze declined.
Conversely, when the gut microbes of these mice were greatly reduced with antibiotics, memory function recovered. In germ-free mice with no gut microbes at all, age-related memory decline appeared much more slowly. Based on this, the researchers concluded that specific components or byproducts produced by an aged gut microbiota could be the cause of memory loss.
In particular, a bacterium called "Parabacteroides goldsteinii" was found more frequently in the intestines of older mice and was linked to memory decline. When this bacterium increases, a substance called medium-chain fatty acids rises, which stimulates immune cells in the gut to produce inflammatory signaling molecules. These molecules impair the function of the vagus nerve's sensory neurons, which transmit the state of organs to the brain, and ultimately affect the hippocampus, a brain region critical for memory formation.
The researchers said that even in older mice with already diminished memory, multiple interventions could restore cognitive function. The simplest approach is to reduce gut microbes with antibiotics, but that has limits for long-term use. So they used bacteriophages (viruses that infect bacteria) targeting specific bacteria, which suppressed the activity of Parabacteroides goldsteinii, lowered medium-chain fatty acid levels, and improved memory.
Another approach is to stimulate the vagus nerve itself. The researchers said they boosted vagus nerve activity using the gut hormones cholecystokinin (CCK) or a glucagon-like peptide-1 (GLP-1) receptor agonist, and memory in older mice improved. GLP-1 receptor agonists are a class of drugs that act similarly to GLP-1, a hormone secreted after meals, to lower blood sugar and aid weight loss; Saxenda and Wegovy are representative examples.
The researchers said, "A treatment that delivers fine electrical stimulation to the vagus nerve is sometimes used for patients with severe epilepsy or those recovering from stroke, and cognitive improvement has been reported among patients who received this procedure," adding, "Ultimately, we hope these findings will be applied in clinical settings to help prevent age-related cognitive decline."
References
Nature (2026), DOI: https://doi.org/10.1038/s41586-026-10191-6