Stanford Scientists Reverse Age-Related Memory Loss by Targeting the Gut

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Health<br>Stanford Scientists Reverse Age-Related Memory Loss by Targeting the Gut<br>By Krista Conger, Stanford MedicineJuly 5, 20261 Comment9 Mins Read

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A new mouse study suggests that age-related memory decline may be influenced by signals traveling from the gut to the brain rather than by brain aging alone. Credit: ShutterstockAging changes gut bacteria in mice, weakening communication between the intestines and the brain. Restoring that connection helped older mice form memories as effectively as young mice.<br>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.<br>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.<br>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.<br>&ldquo;Although memory loss is common with age, it affects people differently and at different ages,&rdquo; said Christoph Thaiss, PhD, assistant professor of pathology. &ldquo;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&rsquo;s actively modulated in the body, and the gastrointestinal tract is a critical regulator of this process.&rdquo;<br>Christoph Thaiss. Credit: Stanford MedicineThe 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.<br>&ldquo;The degree of reversibility of age-related cognitive decline in the animals just by altering gut-brain communication was a surprise,&rdquo; Thaiss said. &ldquo;We tend to think of memory decline as a brain-intrinsic process. But this study indicates that we can enhance memory formation and brain activity by changing the composition of the gastrointestinal tract — a kind of remote control for the brain.&rdquo;<br>Thaiss, who is also a core investigator at Palo Alto-based Arc Institute, is a senior author of the study, which was published in Nature. Maayan Levy, PhD, an assistant professor of pathology and Arc Institute innovation investigator, is the other senior author. Timothy Cox, a graduate student at the University of Pennsylvania, is the lead author of the research.<br>&ldquo;Our study emphasizes that processes in the brain can be modulated through peripheral intervention,&rdquo; Levy said. &ldquo;Since the gastrointestinal tract is easily accessible orally, modulating the abundance of gut microbiome metabolites is a very appealing strategy to control brain function.&rdquo;<br>The call is coming from inside the body<br>The idea that hundreds of bacterial species live in the intestines once seemed surprising. Today, the gut microbiome receives broad attention because it is understood to influence not only digestion, but also wider health. More than 10 years ago, scientists showed that changing the gut microbiomes of rodents could alter their social and cognitive behavior. Thaiss and Levy wanted to know whether a related mechanism might help explain the memory loss and cognitive difficulties often linked to aging.<br>Signals that travel from inside the body to the brain, including messages sent from the intestines through the vagus nerve, are part of a process called interoception. By contrast, signals that come from outside the body through taste, touch, smell, vision, and hearing are called exteroception.<br>&ldquo;Exteroception is basically how we perceive the outside,&rdquo; Thaiss said. &ldquo;We have a lot of detailed knowledge about how this works. But we know much less about how the brain senses what is going on inside the body. We don&rsquo;t know how...