A team of researchers from the Columbia University Medical Center has not only pinpointed a major cause of age-related memory loss, but also demonstrated that this type of memory loss may be reversible.
By examining parts of the brain in deceased subjects between the ages of 33 and 88, the researchers were able to identify which genes change the most with age. Of the 17 genes they identified as possible candidates, the most significant changes occurred in a gene called RbAp48, which showed a distinct decline with age.
Their findings, published online Wednesday in the journal Science Translational Medicine, show that increasing or decreasing the function of RbAp48 has an impact on memory loss.
To test their theory, the team manipulated the expression of that gene in mice. After confirming that there was also a decline of RbAp48 as mice aged, the researchers inhibited the gene and made young mice look like old mice cognitively. The inverse was also true – when they increased the expression of RbAp48 in older mice, their memories began functioning like young mice again.
"We now have a better anatomical and molecular understanding of age-related memory loss," co-senior author Scott Small told U.S. News. "Hopefully that information can be used clinically to better distinguish it from Alzheimer's disease and develop more effective interventions."
It was initially thought that age-related memory loss was an early manifestation of Alzheimer's disease, but recent research has suggested the two originate in different subregions of the hippocampus, the part of the brain that plays a role in converting short-term memory to long-term memory. As such, another goal of the study was to distinguish age-related memory loss from Alzheimer's disease. The part of the hippocampus where the researchers found the deficiency of RbAp48 supported the idea that this area is affected by aging and not Alzheimer's disease.
"There are now tools that could measure its function in humans," Small says. "Down the line the question is, 'Can we rely on the molecular finding to identify pills that increase its function?'"
Such treatments have shown success in rodent test subjects, but the team still has to confirm that they would also be successful in humans.
"Whether these compounds will work in humans is not known," Small said in a statement. "But the broader point is that to develop effective interventions, you first have to find the right target. Now we have a good target, and with the mouse we've developed, we have a way to screen therapies that might be effective, be they pharmaceuticals, nutraceuticals, or physical and cognitive exercises."