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Young blood rejuvenates brains and muscles of old mice

By Sharon Begley

NEW YORK (Reuters) - If three discoveries in mice reported on Sunday are applicable to people, making old brains and old muscles perform like young ones may require simply a blood transfusion.

In two of the studies, giving the blood of young mice to old ones undid age-related impairments in the brain, reversing declines in learning and memory and boosting the creation of new neurons and the ability of the brain to change its structure in response to experience.

The third study found that a protein in the blood of young mice improved the ability of old ones (comparable to a 70-year-old person) to exercise.

"I think the study is quite wonderful," said neuroscientist Eric Kandel of Columbia University, who shared the 2000 Nobel Prize in medicine for his studies on the molecular basis of memory, referring to one of the brain papers.

"It suggests there may be diffusible factors in the blood that are age-dependent, and if you can isolate these substances you might be able to give them as dietary supplements," added Kandel, who was not involved in the studies and at 84 continues to conduct research.

Previous studies had shown that giving young mice blood from old mice impaired their cognitive function. But these discoveries are the first to show the opposite: young blood can reverse age-related impairments.

IMPROVED LEARNING AND MEMORY

In a paper published in Nature Medicine, biologists led by Tony Wyss-Coray of Stanford University and Saul Villeda of the University of California San Francisco described two ways of exposing old mice to young blood. They either injected plasma from 3-month-old mice (young adults) into 18-month olds, which are near the end of their lifespan, or surgically connected the circulatory system of a young mouse to that of an old one.

Old codgers exposed to young blood improved markedly on two standard tests of learning and memory. They made fewer errors navigating a "water maze" and they learned that a specific environment was associated with an electric shock.

Examining the brains of aged mice exposed to young blood, the scientists found both structural and molecular differences from regular old brains.

The treated brains had more "dendritic spines", structures on neurons through which one communicates with another. In addition, the rejuvenated brains produced more of a molecule whose levels rise during learning. And they showed a greater ability to strengthen connections between neurons, the cellular basis for learning and memory.

"We've shown that at least some age-related impairments in brain function are reversible," Villeda said in a statement. "They're not final," since exposure to young blood "counteracts aging at the molecular, structural, functional and cognitive levels in the aged hippocampus," the scientists wrote.

The hippocampus plays a leading role in learning and memory, remembering where we left our keys and what we ate for lunch, and is one of the brain structures most subject to the ravages of both normal aging and Alzheimer's disease.

It is not clear what component of blood acts as a fountain of youth, the Stanford scientists said. But heating the blood abolishes the rejuvenating effects, pointing to some protein whose structure is warped by high temperatures.

The two other mouse studies identified what may be the Ponce de Leon molecule: a growth factor in blood.

In one study, Lee Rubin of Harvard University and colleagues also surgically connected the circulatory systems of an old and a young mouse, they report in a paper to be published by Science on Friday. Result: the old brains created more new neurons in the region that processes smells and their sense of smell became about as sharp as younger mice's.

"Regardless of the age of the old brain . . . young blood is still able to rejuvenate the aged brain," Rubin's team wrote.

Earlier research had suggested that the magic elixir in young blood is a growth factor called GDF11, which is found in both humans and mice.

In the third study, also in Science, biologists led by Harvard's Amy Wagers used similar techniques to expose old mice to young blood, finding that GDF11 improved the ability of old mice to exercise.

Rubin and Wagers each expect to test GDF11 in people within three to five years.

Stanford's Wyss-Coray believes strongly enough in the therapeutic possibilities of young blood that he co-founded a company, Alkahest, to test its effect in humans. "Alkahest" is the name medieval alchemists gave to a hypothetical substance that would act as an "immortal liquor".

(Reporting by Sharon Begley; Editing by Stephen Powell)

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