Researchers identify protein that causes age-related memory loss
US scientists from Columbia University in New York have found out how natural memory loss is caused in old age. A lack of “RbAp48, a histone-binding protein that modifies histone acetylation, plays a major role in this,” reports the research team led by Nobel laureate Eric Kandel in the journal “Science Translational Medicine”.
After investigating the brain of eight deceased patients, the researchers found a noticeable age-related decrease in the protein RbAp48 in the area of the hippocampus, and in trials with mice they checked whether this could possibly trigger the memory loss in old age. It was not about the pathological impairment of memory, as can be seen in Alzheimer's disease, but about the naturally weakening memory in old age. While Alzheimer's has been linked to the build-up of so-called plaques in the brain, the usual age-related memory loss is based on an undersupply of the hippocampus with the protein RbAp48, according to the researchers.
Lack of RbAp48 cause of memory loss
According to the researchers, the examination of the human brain suggested that there may be a connection between the memory impairment in old age and the age-related decline in RbAp48 in the hippocampus or its sub-section in the dentate gyrus. "To test whether the RbAp48 decrease could be responsible for age-related memory loss, we used mice and found that, in line with humans, RbAp48 was less abundant in the dentate gyrus in old mice than in young mice," the researchers write in the journal Science Translational Medicine. In the next step of the investigation, genetically modified mice were generated, in whose brain the RbAp48 proteins were inhibited. "Inhibition of RbAp48 in young mice causes hippocampus-dependent memory deficits similar to those associated with aging," Kandel and colleagues report.
Can age-related memory loss be remedied?
In contrast to Alzheimer's, the age-related memory loss due to an RbAp48 deficiency can generally be remedied by adding RbAp48 or improving absorption, the researchers explain. The tests on the mice had confirmed this. The memory capacity of the aged mice has improved significantly after the RbAp48 release has been artificially increased. This has alleviated the "age-related hippocampus-based memory loss and the changes in histone acetylation", Kandel and colleagues write. "Together, these results show that the dentate gyrus as a region in the hippocampus is subject to age-related changes and we were able to identify molecular mechanisms of cognitive aging that could serve as valid targets for therapeutic intervention," the US scientists concluded.
Age forgetfulness is subject to different laws than Alzheimer's
The current study provides solid evidence that age-forgiveness is subject to different laws than Alzheimer's, Kandel explained. The success in remedying the memory loss of the older mice by increasing the RbAp48 release was particularly encouraging. Here, the researchers see considerable therapeutic potential for the future. So far it remains unclear whether other factors influence age-related memory loss, but it can be assumed that the lack of RbAp48 plays a decisive role, explained Eric Kandel. (fp)
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