Age-related forgetfulness may be due to a deficiency of a brain protein that helps form memories, and targeting the gene that produces the protein could lead to new therapies for old people, new research shows.
Scientists identified the protein, called RbAp48, in human brain cells and showed that inhibiting it in mice made the animals forgetful while raising the protein improved their memories. That suggests that age-related memory loss may be reversible, researchers said.
"All of us are living longer, and we want to stay engaged in a cognitively complex world," said Scott Small, a study author and neurologist at Columbia University. The mouse studies show that too little of the protein is causing memory loss, he said.
The findings also confirm that age-related memory loss is different from the deficits seen in Alzheimer's disease. The research was published Wednesday in the journal Science Translational Medicine.
The researchers took the postmortem brains of eight people ages 33 to 88 who were disease-free and examined the function of 17 genes in a part of the hippocampus, an area that is involved in memory. That section, called the dentate gyrus, has been shown before to change with age. The strongest changes were found in a gene that expressed RbAp48, which declines in function as brains age.
When the researchers suppressed that gene in healthy young mice, the mice performed worse on object recognition and water maze tests.
When the researchers allowed the gene to go back to normal function, the mice's memory improved.
In another group of older mice, researchers used a virus to put extra copies of the RbAp48 gene in the animals' brains. That led them to produce more of the associated protein in their dentate gyruses. Their performance on cognitive tests improved to the levels seen in young mice.
The results suggest that changes in RbAp48 in humans may be a cause of memory loss, Small said. The mouse models here are significant than in other brain disease, since most mammals undergo similar decreases in that gene level naturally as they age, he said.