Blood from human infants appears to improve learning and memory in older mice, a new study shows. The research is the latest in a new field of inquiry, where scientists are looking to see if blood from the very young can rejuvenate the old.
In the study, published April 19 in the journal Nature, researchers from Stanford University found that plasma from blood in human umbilical cords had a stimulatory effect on the brains of mice. The young blood appears to promote to the formation of new neurons in the mouse hippocampus, a brain region heavily involved in forming new memories. Mice injected with human cord plasma also learned a task in a maze more quickly compared with mice injected with saline.
The researchers also sought to identify factors within the blood that could help explain its effect. They singled out a protein called TIMP2, which appears to prompt formation of new neurons and the promotion of neuroplasticity, or the ability to change and learn based on new experiences.
The study suggests there are components of young blood that appear to stimulate the brain—at leasts in mice—which hadn’t previously been established, says lead author Tony Wyss-Coray, a Stanford professor of neurology. Previously Wyss-Coray’s group had shown that injecting old mice with blood from young mice improved their cognition, he says. One motivation for using young human blood in the newer experiment: It is easier to get in larger quantities than that of mice, and scientists don't yet know which of its components could improve cognition.
“Up until this point we had no idea whether there was any of this rejuvenating material in humans,” says first author Joseph Castellano, a Stanford neurology instructor and researcher.
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There are already several trials underway to inject elderly humans with plasma from the very young. Wyss-Coray founded a company called Alkahest that, in collaboration with Stanford, is performing a phase I safety study of this process in 18 people with Alzheimer’s disease, the results of which are currently being analyzed. There is also a startup called Ambrosia looking to see if transfusions of blood from young to older people can improve cognition. That company is the subject of scientific and ethical controversy because it charges participants a hefty sum to be involved and doesn’t include controls given no treatment, which is considered a necessary component of most scientific studies. It clearly remains to be seen if this kind of therapy will help treat problems like Alzheimer’s or to “reverse aging,” as some have put it.
“We need to find out if it works in serious human trials,” Wyss-Coray says.
Rudolph Tanzi, a researcher at Harvard who wasn’t involved in the most recent study, says it takes a “smart” approach to show that young human blood contains factors that cause more “firing and wiring” in the aged mouse brain, but “we still can’t say what that means for cognition in humans. This study has just scratched the surface,” he says.
While most animal studies have suggested some benefit in giving young blood to the elderly, there remain many scientific unknowns. Many of the earlier studies relied on a process called parabiosis, in which pairs of young and old mice had their veins and blood supplies connected. These experiments generally showed a benefit for the older mice, but there may be other reasons besides blood-swapping—like sharing organs—that could explain why this would provide a boost to the elderly animal. A Nature Communications study published in November also suggested transferring blood between young and old mice provided little benefit, and suggested “the inhibitory effects of old blood are more pronounced than the benefits of young.”
The co-lead author of that study, Berkeley researcher Irina Conboy, says this Nature paper suffers from some limitations. For one, the mice given human blood were immunocompromised (otherwise their bodies would reject material from another species), and not as old as mice should be to properly gauge the effect of young plasma. Wyss-Coray disagrees, however, saying that the immunodeficient mice show accelerated aging characteristics that make "them a particularly useful screening tool." Conboy also questioned the wisdom of singling out TIMP-2, which varies amongst different demographic groups and doesn’t decrease much with age, and which some studies have shown to be elevated in cerebrospinal fluid of people with Alzheimer’s and in the brains of those with a degenerative condition called progressive supranuclear palsy. However, other researchers say that TIMP-2 rises in these cases as a response to these diseases (specifically, to prevent protein-degradation), and aren’t likely to be causative.
Castellano concedes that “further studies will be needed to comprehensively characterize TIMP2 [levels and expression] over more precise age ranges and over varied demographic” groups, but defends its use in their study, as its effect on neuroplasticity appear positive and hadn't been studied before. “There’s a lot of complexity here to unravel," he says.
“I think it’s too early to say that adding TIMP-2 to the brain of any adult is going to help them think better,” Tanzi says. And while “it’s all very nice preliminary data,” he says, there are dozens if not hundreds of other proteins that need to be looked at before anybody can say with confidence if these substances—or more generally speaking, a transfusion of blood from young to old—could help treat Alzheimer’s or otherwise be useful in humans.
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