The scientists then sampled 10 more healthy human brains, ranging from 41 to 89 years at the time of death. Once again, the amount of RbAp48 protein declined with age in the dentate gyrus. They next confirmed that RbAp48 protein was also less abundant in the dentate gyrus of old mice compared to young ones.
For the final step, the scientists had to nail down whether the missing protein caused age-related memory loss. They genetically engineered mice whose RbAp48 genes were disabled. Result: The young mice had memories as poor as animals four times their age (the mouse equivalent of late middle age), and they had terrible trouble navigating a water maze or differentiating objects they had seen before from novel ones.
Crucially, the scientists also did the reverse experiment, engineering mice so their brains had extra doses of RbAp48. The mice’s memories returned to the flower of youth.
“With RbAp48, we were able to reverse age-related memory loss in the mice,” said Columbia’s Dr Eric Kandel, who shared the 2000 Nobel Prize in medicine for discoveries of the molecular basis of memory and led the research. “Unlike in Alzheimer’s, there is no significant cell death in age-related memory loss, which gives us hope it can be prevented or reversed.”