IN A GROUNDBREAKING study that could transform our understanding of ageing and cognition, researchers have found a way to restore memory in aged rats by fine-tuning a single molecular process in the brain. The discovery reveals that reducing a specific type of protein modification, known as K63 polyubiquitination, can significantly improve memory performance in older animals.
K63 Polyubiquitination: A Key to Memory in Ageing Brains
The research focused on two critical regions linked to memory and emotion: the hippocampus and the amygdala. Using advanced proteomic analysis, scientists discovered that levels of K63 polyubiquitination rise with age in the hippocampus but fall in the amygdala, two opposing trends that both appear to contribute to memory decline.
When the team used a cutting-edge CRISPR-dCas13 RNA editing system to reduce K63 polyubiquitination in the hippocampus of aged rats, memory performance improved dramatically. The same intervention in middle-aged rats, whose memory was still intact, had no effect, suggesting this molecular change plays a role specifically in age-related cognitive decline.
In the amygdala, further reducing already low K63 levels also enhanced memory in aged animals but did not alter performance in younger ones. These findings reveal a delicate, region-specific balance of protein regulation that may hold the key to maintaining cognitive health over time.
A New Path to Tackling Memory Loss
By demonstrating that targeted molecular editing can reverse memory loss in ageing brains, this research opens an entirely new direction for therapies aimed at neurodegenerative diseases and age-related cognitive decline. Rather than focusing solely on preventing damage, scientists may now explore how to recalibrate the brain’s molecular machinery to restore lost function.
The study’s authors emphasise that while the findings are early and based on animal models, they represent powerful proof that ageing-related memory decline may not be irreversible after all.
Reference
Bae Y et al. Age-related dysregulation of proteasome-independent K63 polyubiquitination in the hippocampus and amygdala. Neuroscience. 2025;580:18-26.
