Gene activity decline behind 'senior moments'

Age-related memory loss could be the result of low levels of protein in the brain, according to researchers at Columbia University Medical Center (CUMC), USA.

The team believes that the protein deficiency is due to decreased gene activity in the hippocampus - a part of the brain that is known to play a crucial role in memory.

The study, published in Science Translational Medicine, involved two research phases. First, the researchers looked at brain cells from an area of the hippocampus called the dentate gyrus in eight healthy adult brains.

'Until now, no one has been able to identify specific molecular defects involved in age-related memory loss in humans', said co-author Scott Small, Professor of Neurology and director of the Alzheimer's Research Center at CUMC.

They identified 17 genes that may be related to memory decay. The most significant changes were found to occur in a gene that controlled the production of the protein RbAp48, where a steady decline in expression was observed from the youngest to the oldest brain.

In order to establish the role of RbAp48 in age-related memory loss, the researchers blocked the RbAp48 gene in healthy young mice and measured their memory proficiency using novel object recognition and water maze memory tasks. They found that when RbAp48 was inhibited, they displayed the same symptoms of memory loss as older mice. When RbAp48 inhibition was stopped, their memory returned to its normal levels.

The researchers were also able to improve memory in older mice by increasing the expression of RbAp48 so that their performance was comparable to that of young mice.

One of the main aims of this study was to distinguish age-related memory loss from Alzheimer's disease.

'It's possible that other changes in the dentate gyrus contribute to this form of memory loss', said Dr Eric Kandel, from Columbia's Mind Brain Behaviour Institute. 'But at the very least, it shows that this protein is a major factor, and it speaks to the fact that age-related memory loss is due to a functional change in neurons of some sort. Unlike with Alzheimer's, there is no significant loss of neurons'.

Dr Simon Ridley, head of research at Alzheimer's Research UK, told the BBC that the findings of these studies are promising, but are not yet as 'clear-cut' in real life. 'Separating early changes in Alzheimer's from age-related memory decline in the clinic still presents a challenge, but understanding more about the mechanisms of each process will drive progress in this area', he said.