Mice Vampirism is a bloody fountain of youth – Young blood can rejuvenate muscle, brain, heart and blood vessels

NExtbigfuture covered research last year on the blood protein GDF11 from young mice which seems to rejuvenate older mice.

In recent years, researchers studying mice found that giving old animals blood from young ones can reverse some signs of aging, and last year one team identified a growth factor in the blood that they think is partly responsible for the anti-aging effect on a specific tissue–the heart. Now that group has shown this same factor can also rejuvenate muscle and the brain.

“This is the first demonstration of a rejuvenation factor” that is naturally produced, declines with age, and reverses aging in multiple tissues, says Harvard stem cell researcher Amy Wagers, who led efforts to isolate and study the protein. Independently, another team has found that simply injecting plasma from young mice into old mice can boost learning.

So far only two other interventions–the drug rapamycin and caloric restriction—have been shown convincingly to slow or reverse aging in multiple tissues, says Kaeberlein. Wagers points out that GDF11 could be safer than a drug because it’s found naturally in blood. Harvard has filed for patents on GDF11, and Wagers says she and her colleagues are “in the process of talking with people” about commercializing it to treat diseases such as Alzheimer’s and heart disease. Giving GDF11 itself “would require huge amounts of protein,” Wagers says, so it may be better to use a modified form or to target the GDF11 pathway with a different molecule. “These are tractable problems,” Wagers says. “The most important hurdle was figuring out a pathway to go after.”

Already, GDF11 has a potential rival treatment. In Nature Medicine today, Wyss-Coray’s lab at Stanford reports that parabiosis can rejuvenate another part of the mouse brain, the hippocampus, where memories are made and stored. Old mice that underwent parabiosis formed more new connections between nerve cells there. Although Wyss-Coray’s group has not yet isolated any rejuvenation factors from the young blood, they have found what might be an alternative. When Wyss-Coray’s team tried a simpler experiment than parabiosis—giving old mice injections of plasma from young mice—they saw similar effects on the hippocampal neurons. The old mice also performed significantly better than untreated animals on tests of learning and memory.

Plasma is given routinely to patients, so trials of this approach, unlike testing a new protein, would not require U.S. Food and Drug Administration approval, Wyss-Coray says. His group has started a company that is planning a small clinical trial that would give Alzheimer’s patients a series of injections of plasma from young donors. In mouse models of Alzheimer’s, they have already seen positive effects, he says.

Nature Medicine – Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice.

As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts—in which circulatory systems of young and aged animals are connected—identified synaptic plasticity–related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function.

19 pages of supplemental information

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