As you age, your brain slows down. You may forget where you left your glasses or have trouble picking up a new skill. Now there’s hope from rodent experiments that some of these declines could be reversed—but it takes guts. New research shows a transplant of gut microbes, in the form of feces, from young mice to old ones can turn back the clock on the aging brain.
The study is “a tour de force” for the scope of data it collected, says Sean Gibbons, a gut microbe researcher at the Institute for Systems Biology. Still, he says, more work must be done before anyone considers doing anything similar with humans.
The bacteria in our intestines influence everything from our daily moods to our overall health. This “gut microbiome” also changes over the course of our lives. But whereas some studies have shown young blood can have rejuvenating effects on old mice, the microbiome’s impact on age-related declines hasn’t been clear.
To test whether a young microbiome could reverse signs of aging, researchers took fecal samples from 3- to 4-month-old mice, the equivalent of young adults, and transplanted them into 20-month-old animals—ancient by mouse standards. The scientists fed a slurry of feces to the old mice using a feeding tube twice a week for 8 weeks. As controls, old mice received transplants from fellow old mice, and young from young.
The first thing the team noticed was that the gut microbiomes of the old mice given young mouse microbes began to resemble those of the younger ones. The common gut microbe Enterococcus became much more abundant in old mice, just as it is in young mice, for example.
There were changes in the brain as well. The hippocampus of old mice—a region of the brain associated with learning and memory—became more physically and chemically similar to the hippocampus of young mice. The old mice that received young mouse poop also learned to solve mazes faster and were better at remembering the maze layout on subsequent attempts, the team reports today in Nature Aging. None of these effects was seen in old mice given old mouse feces.
“It’s almost like … we could press the rewind button on the aging process,” says John Cryan, a neuroscientist at University College Cork who led the new study.
However, some things did not noticeably change for older mice given young feces. Many types of gut bacteria remained the same, for example, and the old mice didn’t become more social, which Cryan found surprising, because he’s seen the microbiome impact social interactions in other studies.
Arya Biragyn, a molecular biologist at the National Institute on Aging, says he would have liked the team to have done more to show the microbiomes had actually changed in the older mice. Because the researchers checked for differences in the gut microbiome soon after the transplants, there’s no way to know whether the new microbes had truly moved in or were just passing through, he argues.
Gibbons also notes that the field of fecal transplants in mice remains a mixed bag. Whereas some studies have found such procedures appear to be beneficial, he says, at least one has found that they can lead to cognitive declines.
Cryan himself cautions about jumping the gun to humans, given that the study was entirely based on rodents. Still, he argues, the work offers hope. “The good thing about your microbiome—as opposed to your genome—is that you can change it.”
sciencemag.org, 9 August 2021