For decades, age-related memory loss has largely been viewed as a problem that begins in the brain. But growing evidence suggests that some of the processes shaping cognition may start much farther south — in the gut, home to trillions of microbes that help regulate everything from digestion to immunity.

A new mouse study from researchers at Stanford Medicine and the Arc Institute in Palo Alto, California, points to a surprising gut-brain connection behind cognitive aging.

The team found that age-related changes in gut bacteria can interfere with signals traveling along the vagus nerve, a major communication highway linking the gastrointestinal tract and the brain. Their findings suggest that memory decline may be influenced by changes outside the brain itself, opening new possibilities for preserving cognitive function later in life.

“Although memory loss is common with age, it affects people differently and at different ages,” said Christoph Thaiss, PhD, assistant professor of pathology. “We wanted to understand why some very old people remain cognitively sharp while other people see significant declines beginning in their 50s or 60s. What we learned is that the timeline of memory decline is not hardwired; it’s actively modulated in the body, and the gastrointestinal tract is a critical regulator of this process.”

The study found that the gut microbiome, the natural community of bacteria living in the intestine, changes as mice grow older. Some bacterial species become more common while others decline. Immune cells in the gastrointestinal tract detect these changes and trigger inflammation that weakens signaling through the vagus nerve to the hippocampus, the brain region involved in memory formation and spatial navigation. When researchers stimulated vagus nerve activity in older mice, the animals regained the ability to remember unfamiliar objects and escape mazes as well as younger mice.