Plasma component restores some of youth’s vibrancy to elderly mice
Vampires knew it all along, but now scientists have discovered that young blood can keep an old brain sharp. Plasma or blood from a young mouse — or even a single protein from plasma — rejuvenates sluggish bodies and minds in a host of ways, three new studies find.
Throughout the ages, people have searched far and wide for an elixir that replenishes the body. “Maybe they were just looking too far,” says Tony Wyss-Coray of Stanford University School of Medicine, coauthor of a May 4 study in Nature Medicine.
Young blood recharges old neurons, improving mice’s ability to learn and remember things, Wyss-Coray and colleagues found. Two other papers, appearing May 4 in Science, identified a particular ingredient in young blood that improves both brain and muscles.
Scientists had already found benefits of young plasma on other tissues, such as the heart, liver and pancreas. Finding that the brain can be refreshed too may point out ways to counter age-related declines, either with plasma from young people or drugs made to mimic important parts of it, scientists say.
That the elderly brain can be rescued suggests that cognitive decline with aging may be avoidable, says Lee Rubin of Harvard University, coauthor of one of the Science papers. “It’s not a unilateral descent into complete degeneration in an inexorable kind of way.”
The premise of the experiments was deceptively simple: Scientists surgically linked the circulatory system of an old mouse to that of a young one, allowing their blood to mingle. In earlier experiments, Wyss-Coray and colleagues had found that this surgery to make mouse Siamese twins is bad for the young mouse. Ingredients in old blood harm the young mouse’s brain, the researchers reported in 2011.
This time around, he and his colleagues looked for benefits that young blood might confer on older mice.
In the experiment, 18-month-old mice — the rodent equivalent of about a 55- to 70-year-old person – were tethered to 3-month-old mice, the equivalent of about a 20- to 30-year-old. The infusion of young blood kicked off a cascade of changes in the behavior of genes important for neuron behavior, the team found. And the neurons themselves appeared to sprout more docking places for other neurons to connect, a property of healthy neurons in young brains. These changes weren’t present in old mice that had been surgically connected to other old mice.
Directly injecting old mice with plasma from young mice created benefits too — no surgery required. After receiving intravenous injections of young plasma eight times over 24 days, old mice were better at remembering the location of a hidden platform and responded more strongly to a scary environment, compared with old mice that had received injections of plasma from other old mice. No improvements occurred when the plasma was heated before it was injected, a process that can destroy sensitive proteins.
In a different experiment that connected mouse circulatory systems, Rubin and colleagues found that young blood increases the rate of cell birth in a brain region of the mouse called the subventricular zone. This region gives birth to cells that help a mouse smell. Old mice surgically linked to a young mouse were better able to discriminate odors, the team found.
The benefits weren’t restricted to the smell system. Rubin and colleagues found that new blood remodels blood vessels in a way that boosts flow. “The increase in blood vessels and blood flow is all over the brain, so we think that there will be other benefits to the older brain,” he says.
Rubin thinks that the positive effects of young blood probably last several weeks. “Maybe you wouldn’t have to be a Dracula feeding on fresh blood every day.” (Here’s another way vampires might have gone wrong: The beneficial molecules probably wouldn’t survive a trip through the digestive system, Wyss-Coray says.)
Of course, there would be no need to drain blood from young donors (or victims) if the key ingredients could be isolated. The Science studies identify one such contender: a protein called GDF11, which normally declines with age. Delivering this molecule partially mimicked some of the gains in the brain, Rubin and colleagues found, and in skeletal muscle, as described in a paper by Amy Wagers of Harvard Medical School and colleagues.
In the brain, GDF11 alone remodeled brain blood vessels and enhanced the birthrate of new cells in the subventricular zone, Rubin and colleagues found. But it’s unlikely that GDF11 acts alone. Perhaps the benefits come from both a boost in positive ingredients in the young blood and a reduction of harmful ingredients in old blood, Rubin says.
“All of these studies concentrate on what’s being enhanced,” says immunotherapy expert Dobri Kiprov of California Pacific Medical Center in San Francisco. “What they address to a much lesser extent is what’s being removed.” Inflammatory molecules that rise with age may be important to consider, he says.
The results suggest that one day, designed molecules may stave off decline in the entire body. But much more work needs to be done to reach that point. Moving the research into human experiments will be difficult, but Wyss-Coray has started a biotechnology company, Alkahest, and plans to test the effects of plasma from young donors on people with Alzheimer’s disease. He hopes to start in a few months.
S.A. Villeda et al. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nature Medicine. Published online May 4, 2014. doi:10.1038/nm.3569
L. Katsimpardi et al. Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Science. Published online May 4, 2014. doi: 10.1126/science.1251141
M. Sinha et al. Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science. Published online May 4, 2014. doi: 10.1126/science.1251152.
L. Sanders. Brain chemicals help worms live long and prosper. Science News. Vol. 185, April 19, 2014, p. 10.
S. Villeda et al. The aging system milieu negatively regulates neurogenesis and cognitive function. Nature, Vol. 477, September 1, 2011. doi:10.1038/nature10357.