Mouse Brains Mirror Human Aging: Insights for Cognitive Decline Research

Scientists have discovered striking similarities in how the brains of mice and humans age, a finding that could accelerate research into preventing age-related cognitive decline. The research, published today in the Proceedings of the National Academy of Sciences, utilized advanced brain scanning techniques to track changes in mice over their lifespans, revealing patterns mirroring those observed in human brains.

Researchers at Columbia’s Zuckerman Institute and the University of Texas at Dallas employed functional magnetic resonance imaging (fMRI) to monitor brain activity in 82 mice from the equivalent of human ages 18 to 70. The study overcame significant technical hurdles to achieve this, including using fMRI scanners with magnetic fields more than three times stronger than those typically used for human brain imaging and developing methods to scan awake mice – a rare capability.

The team found that, as mice aged, the specialized modules within their brains – areas responsible for specific tasks like color perception or facial recognition – became less distinct in their function, a phenomenon previously observed in aging humans and linked to memory loss and other cognitive impairments. “The way the brain’s modules relate together as a whole is a measure of brain health that appears to apply similarly in both humans and mice,” said Ezra Winter-Nelson, a doctoral student at the University of Texas at Dallas and lead author of the study.

While the findings highlight shared aging patterns, they as well revealed key differences. Mouse brain modules exhibited less communication with each other compared to human brains. Gagan Wig, an associate professor of psychology at the University of Texas at Dallas and co-senior author, suggested this greater integration in human brains may contribute to uniquely human cognitive abilities, but also potentially increase vulnerability to age-related decline. “So while we as humans have this ability to integrate information across more widely distributed parts of the brain, that may leave us more vulnerable to brain and cognitive decline when compared to mice,” Wig stated.

Itamar Kahn, a principal investigator at Columbia’s Zuckerman Institute and co-senior author, emphasized the potential of using mice as a model for studying brain aging. “By looking at mice, we can see if, say, a change in diet in their youth has an effect on them in old age, and we don’t have to wait 80 years for results as we would with humans,” Kahn explained. The researchers acknowledge that their study focused on a single strain of lab mice and plan to investigate other strains to understand how genetic factors influence the aging process.

The research builds on previous neuroscience work with mice, which has sometimes faced criticism for lacking relevance to human conditions. Kahn noted that this study differs by focusing on brain networks rather than cellular-level changes, potentially offering a more translatable approach to developing therapies for age-related brain disorders. The Zuckerman Institute, led by Daphna Shohamy, focuses on understanding the biological basis of mind and behavior, with the goal of improving human health and well-being.