Reactivating a gene that supports memory

A second study, published in the Brain Research Bulletin and led by Jarome with doctoral student Shannon Kincaid, focused on IGF2, a growth-factor gene that supports memory formation. As the brain ages, IGF2 activity drops as the gene becomes chemically silenced in the hippocampus.

“IGF2 is one of a small number of genes in our DNA that’s imprinted, which means it’s expressed from only one parental copy,” Jarome said. “When that single copy starts to shut down with age, you lose its benefit.”

The researchers found that this silencing happens through DNA methylation, a natural process in which chemical tags accumulate on the gene and switch it off. Using a precise gene-editing tool, CRISPR-dCas9, they removed those tags and reactivated the gene. The result was better memory in older rats.

“We essentially turned the gene back on,” Jarome said. “When we did that, the older animals performed much better. Middle-aged animals that didn’t yet have memory problems weren’t affected, which tells us timing matters. You have to intervene when things start to go wrong.”

Together, the two studies show that memory loss is not caused by a single molecule or pathway and that multiple molecular systems likely contribute to how the brain ages.

“We tend to look at one molecule at a time, but the reality is that many things are happening at once,” he said. “If we want to understand why memory declines with age or why we develop Alzheimer’s disease, we have to look at the broader picture.”

Collaborative, graduate-led research

Both studies were driven by graduate researchers in Jarome’s lab and supported through collaborations with scientists at Rosalind Franklin University, Indiana University, and Penn State. Yeeun Bae, who completed her doctoral work with Jarome in the School of Animal Sciences, led the study on K63 polyubiquitination. Shannon Kincaid, a doctoral student in the same program, led the study on IGF2.

“These projects represent the kind of graduate-led, collaborative research that defines our work,” Jarome said. “Our students are deeply involved in designing experiments, analyzing data, and helping shape the scientific questions we pursue.”

The research was supported by the National Institutes of Health and the American Federation for Aging Research.

“Everyone has some memory decline as they get older,” he said. “But when it becomes abnormal, the risk for Alzheimer’s disease rises. What we’re learning is that some of those changes happening at a molecular level can be corrected — and that gives us a path forward to potential treatments.”

Original study: https://doi.org/10.1016/j.neuroscience.2025.06.032

Original study: https://doi.org/10.1016/j.brainresbull.2025.111509