Healthcare (Commonwealth Union) – Memory decline might not just be an inevitable part of aging. New findings from Virginia Tech reveal that it’s linked to precise molecular shifts in the brain — and that fine-tuning these mechanisms could enhance memory function.
In two related studies, Associate Professor Timothy Jarome from the College of Agriculture and Life Sciences’ School of Animal Sciences, together with his graduate students, applied gene-editing techniques to address these age-related brain changes and boost memory performance in older subjects.
Jarome, who holds an appointment in the School of Neuroscience as well indicated that memory loss has an impact on over a third of individuals who are over 70 years old, and it is a key risk factor for Alzheimer’s disease.
He further pointed out that research indicates that memory decline is associated with specific molecular alterations that can be targeted and researched and if can can know what is driving it at the molecular level, they can begin to grasp what goes wrong in dementia and eventually utilise that knowledge to bring about new ways of treatment.
In the first study, featured in the journal Neuroscience and led by Timothy Jarome along with doctoral student Yeeun Bae, researchers explored a mechanism known as K63 polyubiquitination — a molecular tagging process that directs how brain proteins function. Under normal conditions, this system supports communication between brain cells and aids in memory formation.
The team discovered that aging interferes with K63 polyubiquitination in two key brain regions. In the hippocampus, which governs memory creation and retrieval, K63 polyubiquitination levels rise with age. By using the CRISPR-dCas13 RNA editing tool to lower these levels, the scientists successfully enhanced memory in older rats which were used in the study.
In contrast, within the amygdala, a region tied to emotional memory, K63 polyubiquitination naturally decreases over time. When the researchers further reduced its activity there, they again observed improvements in memory among older rats.
“Together, these findings reveal the important functions of K63 polyubiquitination in the brain’s aging process,” explained Jarome. “In both regions, adjusting this one molecular process helped improve memory.”
A second study, featured in the Brain Research Bulletin and led by Jarome alongside doctoral student Shannon Kincaid, explored the role of IGF2 — a growth factor gene crucial for memory development. As the brain ages, IGF2 activity declines because the gene becomes chemically silenced within the hippocampus.
Jarome indicated that IGF2 is part of a rare group of genes in our DNA known as imprinted genes, meaning only one copy—either maternal or paternal—is active. He pointed out that when that single active copy begins to shut down with age, we lose its positive effects.
The team discovered that this silencing occurs through DNA methylation, a natural mechanism where chemical markers attach to the gene and deactivate it. By applying a precise gene-editing method known as CRISPR-dCas9, they were able to remove these markers and reactivate IGF2. The intervention led to improved memory in older rats.
Jarome stated that in essence, we switched the gene back on. He pointed out that once they did that, the older rats showed marked improvements in memory. Interestingly, middle-aged rats without noticeable memory decline were unaffected — suggesting that timing is key and there is a need to step in as soon as the system begins to fail.
Together, both studies reveal that memory loss is not caused by a single molecule or pathway and that many molecular systems possibly play a role in the way 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 explained. “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.”
