Brain of mice ages like a human’s

The human brain works as a network of specialized modules, each responsible for specific functions such as face recognition, color perception, and speech processing. However, as we age, these modules lose their distinct specialization, and the connections between them become blurred. Previous studies have observed this degradation in humans and linked it to memory decline and other cognitive impairments, but the molecular and cellular mechanisms underlying this process remain poorly understood. Experiments on humans do not allow you to quickly check how a diet in youth or a specific genetic mutation will affect the brain after half a century.

A team led by Itamar Kahn from the Zuckerman Institute and Gaghan Vig from the University of Texas at Dallas decided to find out whether a similar picture is observed in mice, whose brain is about 3,000 times smaller than the human brain in volume. To do this, the researchers had to adapt the technology of functional magnetic resonance imaging: They used scanners with a magnetic field that was more than three times higher than the standard for clinical devices, which allowed them to distinguish between small structures in the rodents’ tiny brains. Kahn’s lab is one of the few in the world that can perform fMRI scans on awake mice, rather than on animals that are under anesthesia, which brings the experimental conditions closer to those used for human scans.

The researchers tracked 82 mice from three months to 20 months of age, which roughly corresponds to the range of 18 to 70 years in humans, and scanned their brains at regular intervals. The results confirmed the hypothesis: as the mice aged, their brain modules lost their specialization and became less coordinated, mirroring the age-related pattern that neuroscientists have documented in humans.

“The way the brain modules relate to each other as a whole turned out to be a measure of brain health that applies to both humans and mice,” explained Ezra Winter-Nelson, a doctoral student in Wig’s lab and the first author of the paper.

At the same time, the differences between the two species were also revealing. In humans, the brain modules are more closely connected than in mice, and Wig believes that this deeper integration is the basis for the cognitive abilities that humans have developed more than rodents. The downside of this integration is that the age-related loss of module specialization is faster in humans than in mice, and it may make the human brain more vulnerable to cognitive decline.

The practical value of this discovery is that scientists can now model age-related brain aging in mice and test how genetics, environment, diet, or experimental drugs affect its trajectory, obtaining results in months instead of decades. “We can see if, say, a change in diet in youth will affect the state of the brain in old age, and we won’t have to wait 80 years, as is the case with humans,” Kang said.

The authors stipulate that so far they have worked with only one line of laboratory mice and plan to expand the research to other lines that are known to age differently in order to find out how the genetic background modifies age-related changes in brain networks.

Previous neuroscience studies on mice have been repeatedly criticized for their limited clinical relevance to humans, and much of this criticism has focused on studies that focused on changes at the single-cell level. Kahn emphasized that his team is analyzing the brain at the network level, and that a combination of network and cellular approaches may be more effective in developing therapies that can be applied not only to mice but also to humans.