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Scientists Discover Key to Normal Memory Lapses in Seniors

FILE- Researcher holds human brain in laboratory at Northwestern University's cognitive neurology and Alzheimer's disease center, Chicago, July 29, 2013.
FILE- Researcher holds human brain in laboratory at Northwestern University's cognitive neurology and Alzheimer's disease center, Chicago, July 29, 2013.
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Reuters
— Scientists have good news for all the older adults who occasionally forget why they walked into a room — and panic that they are getting Alzheimer's disease.
Not only is age-related memory loss a syndrome in its own right and completely unrelated to that dread disease, but unlike Alzheimer's it may be reversible or even preventable, researchers led by a Nobel laureate said in a study published on Wednesday.

Using human brains that had been donated to science as well as the brains of lab mice, the study for the first time pinpointed the molecular defects that cause cognitive aging.

In an unusual ray of hope for a field that has had almost nothing to offer older adults whose memory is failing, the study's authors conclude that drugs, foods or even behaviors might be identified that affect those molecular mechanisms, helping to restore memory.

Any such interventions would represent a significant advance over the paltry offerings science has come up with so far to prevent memory decline, such as advice to keep cognitively active and healthy — which helps some people, but not all, and has only a flimsy scientific foundation. By identifying the “where did I park the car?” molecule, the discovery could also kick-start the mostly moribund efforts to develop drugs to slow or roll back the memory lapses that accompany normal aging.

“This is a lovely set of studies,” said Molly Wagster of the National Institute on Aging, an expert on normal age-related memory decline who was not involved in the new study. “They provide clues to the underlying mechanism of age-related memory decline and will, hopefully, move us down the road toward targeted therapeutics.”

About 40 percent of Americans age 85 and older say they experience some memory loss, a 2009 survey by the Pew Research Center found, as did 27 percent of those 75 to 84 and 20 percent of those ages 65 to 74.

Brain bank

The researchers began with eight brains from the New York Brain Bank at Columbia University donated by people aged 33 to 88 who were free of brain disease when they died. They extracted two structures in the hippocampus, a vital cog in the brain's memory machinery: the dentate gyrus, a boomerang-shaped region whose function declines with age but is not affected by Alzheimer's, and the entorhinal cortex, which is largely unaffected by aging but is where Alzheimer's first takes hold, killing neurons.

The scientists then measured which genes had been active in each structure, and found one suspicious difference: 17 genes in the dentate gyrus became more active, or less, as the age of the brain increased.

The most significant change was that the gene for a protein called RbAp48 had essentially retired: The gene's activity tailed off dramatically the older a brain got. As a result, old brains had about half the RbAp48 of young brains, the scientists report online in the journal Science Translational Medicine.

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.”

Exactly how RbAp48 does that is not clear. The protein acts as a sort of genetic master key: By causing chromosomes to loosen their hold on the molecular spool they are wound around like thread, it allows genes to be turned on. Among the activated genes, Kandel explained, are those involved in forming memories.

The emerging picture is that levels of RbAp48 decline with age, allowing chromosomes to maintain a death grip on their spools. Memory genes remain dormant, and you can't remember that you promised your spouse you would make dinner.

The researchers plan to see what social and dietary factors might boost RbAp48 in mice, said Kandel, who will be 84 in November. Pharmaceuticals, nutraceuticals, physical and cognitive exercise are all candidates, said Columbia's Dr. Scott Small, co-senior author of the study.

Testing such interventions in mice should be more useful to humans than tests of drugs for Alzheimer's, he said. RbAp48 “is different,” Small said. “Alzheimer's does not occur naturally in the mouse. Here, we've caused age-related memory loss in the mouse, and we've shown it to be relevant to human aging.”

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by: Julie from: New York
August 30, 2013 7:09 AM
Staying healthy is essential especially as you age and the best way to do that is to stay physically active, eat the right things and keep mentally sharp. I just checked out the site Retirement And Good Living that has some great pages and post on exercise, mental health and nutrition as well as many other retirement related topics including various games to keep your mind active.

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