Scientists at Virginia Tech report that tuning specific molecular pathways with CRISPR-based tools improved memory in older rats across two peer‑reviewed studies, pointing to possible routes for tackling age‑related cognitive decline.
New research from Virginia Tech indicates that age‑related memory problems may be modifiable. In two studies led by associate professor Timothy Jarome and graduate researchers, the team used CRISPR tools to adjust molecular changes linked to memory decline in aging rats, a common model for human brain aging. (sciencedaily.com)
In the first study, published in Neuroscience on August 6, 2025, Jarome and doctoral student Yeeun Bae examined lysine‑63 (K63) polyubiquitination, a protein‑tagging process involved in neuron communication. They found that K63 tagging increases with age in the hippocampus, which supports memory formation and retrieval, but decreases in the amygdala, which is important for emotional memory. Using a CRISPR‑dCas13 RNA system, the researchers reduced K63 polyubiquitination in the hippocampus and further lowered it in the amygdala of aged rats, which improved contextual fear‑memory performance; these manipulations did not affect middle‑aged rats. “Adjusting this one molecular process helped improve memory,” Jarome said. (pubmed.ncbi.nlm.nih.gov)
A second paper, published October 1, 2025, in Brain Research Bulletin, targeted the imprinted memory‑supporting gene IGF2, whose activity declines in the aging hippocampus. The team showed that IGF2 is silenced with age via DNA methylation and used CRISPR‑dCas9 to increase 5‑hydroxymethylation at the Igf2 promoter—an epigenetic edit that reactivated the gene. Reactivating IGF2 improved memory and long‑term potentiation in aged, but not middle‑aged, rats. “We essentially turned the gene back on,” Jarome said. (pubmed.ncbi.nlm.nih.gov)
Taken together, the studies suggest that multiple molecular systems contribute to memory decline in aging and that precise interventions can restore performance in old animals. About one‑third of U.S. adults over 70 experience cognitive decline, underscoring the need for such mechanistic insights; the authors note that the work could help illuminate what goes wrong in dementia, though the findings are limited to animal models and far from clinical application. (pubmed.ncbi.nlm.nih.gov)
According to Virginia Tech, the projects were led by graduate researchers and carried out with collaborators at Rosalind Franklin University, Indiana University, and Penn State. The university also reports funding from the National Institutes of Health and the American Federation for Aging Research. NIH support is additionally documented in the journal records via listed grant numbers. (sciencedaily.com)
