A literal infusion of some "young blood" has the ability to turn back the clock and restore the mental capabilities of old mice, according to a study conducted by researchers at the Stanford University School of Medicine. If similar results are seen in humans, the simple technique could lead to new treatments for forms of dementia, such as Alzheimer's disease.
The study builds on previous research conducted in 2011 that showed key regions of the brains of old mice produced more nerve cells when exposed to blood from young mice than did old mice exposed to blood from old mice. Previous experiments also showed that the opposite effect in terms of nerve-cell production was seen when the brains of young mice were exposed to blood from old mice, with their ability to navigate their environments also reduced.
What these previous experiments failed to assess was the impact of young mouse blood on the behavior of older mice. So for the new study, in addition to using sophisticated techniques to check for changes within nerve circuits and individual cells, the researchers conducted a simpler standard laboratory test of spatial memory, comparing the performance of older mice that received infusions of plasma from young versus old mice, or no plasma at all.
"This could have been done 20 years ago,” said Tony Wyss-Coray, PhD, the senior author of the study who has founded a company, Alkahest, to examine the potential therapeutic benefits of the findings. "You don’t need to know anything about how the brain works. You just give an old mouse young blood and see if the animal is smarter than before. It’s just that nobody did it."
In tests in which older mice were trained to quickly locate a submerged platform in a water-filled container, requiring them to orient themselves using memory cues provided by their surroundings, those that had been injected intravenously with plasma from young mice performed much better than older mice that didn't receive any plasma and those that received plasma from older mice.
Similar results were seen in another test in which mice were trained to freeze in fear when placed in a particular environment. Those mice that better recognize the environment freeze for longer, so young mice typically freeze for longer than older mice. That was still the case, but the length of time older mice given young plasma froze increased significantly.
"We’ve shown that at least some age-related impairments in brain function are reversible," said Saul Villeda, PhD, the lead author of the study. "They’re not final."
Although it is still unclear exactly what factors in the plasma are responsible for the boost in brain function, the team says a hint is provided by the fact that the improvements disappeared if the plasma given to the older mice had been subjected to high temperatures. Because high temperatures can change the nature of proteins, this suggests a blood-borne protein, or group of proteins, may be behind the cognitive improvements.
Wyss-Coray points out that it isn't yet known whether the same results will be seen in humans, but putting the approach to the test through a clinical trial is a near-term goal of his company.
The team's study appears in the journal Nature Medicine.
Source: Stanford School of Medicine
