OLD Gut, YOUNG Gut: What's the Difference?

Growing old can be a pain in the neck—or a pain in the stomach. As you age, you’re more prone to constipation, acid reflux, and bowel control problems. Some of that’s due to medications older people are more likely to take, chronic diseases, or inactivity, but it may also be due to changes in the gut, according to Laren Becker, MD, PhD. A physician-scientist in the Division of Gastroenterology & Hepatology and an instructor of medicine, Becker has advised undergraduate and graduate students during their research rotations during the past several years.

Recently, Becker studied the guts of mice, which led him to discover another factor driving gut problems: immune cells change with age and drive inflammation, which in turn, change the function of the GI tract.

“If this is also true in humans, and we could find a way to prevent these changes, we wouldn’t have this overwhelming burden of GI problems in older people,” says Becker, whose research was published in Gut in February 2017.

Immune System to Blame

Like every other system in the body, the digestive system is chock full of immune cells that patrol for invading pathogens that we might have swallowed with our food. In the muscle layer of the gut, the most plentiful of these cells are muscularis macrophages, immune cells that surround the nerve cells of the intestines. Becker wanted to study how these macrophages—which, aside from their defensive role, are known to help coordinate the cross-talk between the nervous system and GI tract—change during aging. In initial studies, he turned to young and old mice to make the comparisons. Here’s what he found:

To sum up, the entire population of muscularis macrophages in the gut changed as the mice aged, promoting inflammation and killing off lots of neurons in the gut. This could lead to all sorts of gastrointestinal conditions, Becker says, since those neurons are critical to keeping the gut moving.

"Targeting these cells could be a way to RESTORE many parts of the body to a more youthful state"

Next, Becker wants to see whether the findings made in mice hold true in humans. He’s also curious which factors are initially responsible for the shift in FoxO3 levels and macrophage function. The microbiome—the collection of bacteria that live in your gut—may play a role, for instance. And more work is needed to reveal whether macrophages in other organs of the body make similar shifts toward inflammation during aging.

“If we have a better understanding of how macrophages change with age, targeting these cells could be a way to restore many parts of the body to a more youthful state,” Becker says.