New research finds infusing aging mice with the blood of young mice appears to recharge the brain so it functions more like a younger one. Led by Stanford School of Medicine in California, the study introduces the idea that age-related decline is reversible, pointing the way to potential new treatments for Alzheimer's disease and other dementias.
In the journal Nature Medicine, senior author Tony Wyss-Coray and colleagues describe how they infused plasma (blood stripped of cells) from young mice into older mice and found they performed better in spatial memory tests than older mice that had received plasma from other older mice, or none at all.
The main purpose of the study was to use sophisticated methods to test a number of important molecular and biological changes that occur in the brains of older mice when they share the blood of younger mice.
But the team decided to include an extra test on memory performance, and this is how they made their discovery, as Prof. Wyss-Coray, who is also senior research career scientist at the Veterans Affairs Palo Alto Health Care System, explains:
"This could have been done 20 years ago. 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."
Study examined pairs of mice with shared blood supply
The study involved examining pairs of mice whose circulation systems were surgically conjoined. So-called parabiotic mice share a pooled blood supply. The experiments involved two kinds of pairs: a young mouse paired with an old mouse, and two old mice paired together.
The team has published work on the effect of blood on aging using parabiotic mice before. For instance, in a study reported in Nature in 2011 they concluded blood factors appear to cause aging in brains of mice.
In that study, they showed how more new cells grew in key parts of the brain of older mice paired with young mice than in old mice paired with other old mice. And conversely, they also found exposing young mice to blood from old mice had the opposite result on nerve cell production, and the young mice were less able to find their way around their environments.
But what the team had not done previously was measure the effect of young blood on the brains of the older mice in simple memory tests. In this latest study, they did both - they looked for changes in brain circuits and cells, and they tested changes in learning and memory.
Researchers focused on changes to the hippocampus
When infused with plasma from younger mice, the older mice performed much better in spatial memory tests.
The researchers were particularly interested in examining what happened to the hippocampus in the brains of the parabiotic mice. The hippocampus is important for recalling and recognizing spatial patterns, both in mice and humans.
This part of the brain. Prof. Wyss-Coray explains, is the part you use when you are trying "to find your car in a parking lot or navigate around a city without using your GPS system."
The hippocampus can change depending on brain activity. For instance, one study found brain changes in London cab drivers. Trainees who after 3 or 4 years passed the exam called "The Knowledge," showed an increase in grey matter at the back of the hippocampus compared to the ones who did not pass the exam.
The hippocampus is also very vulnerable to aging. Its function erodes in all brains as they age, but it occurs faster in people with dementia like Alzheimer's disease, who eventually cannot form new memories.
When they looked at the variously paired parabiotic mice, the researchers found consistent differences in the way the hippocampus behaved biochemically, and electrically, as well as what it looked like.
Hippocampus was 'younger looking' in older mice infused with young blood
The hippocampi of older mice were more similar to those of younger mice when they were paired with younger mice than with older mice. Also, when paired with younger mice, the hippocampi of older mice made more chemicals linked to learning, than those of older mice paired with other older mice.
The nerve cells in older mice paired with younger mice were also more able to stronger connections to other nerve cells, compared with the nerve cells in the older pairs. These connections are an important feature for making new memories and learning.
Prof. Wyss-Coray says it was "as if these old brains were recharged by young blood."
As well as examining these various changes in the brains of the mice, the team put differently aged mice through tests where they had to quickly orient themselves in new and challenging situations - using memory cues from their surroundings.
The older mice, as expected, tended to perform worse than the younger mice, as they did when infused with plasma from other older mice.
But, when infused with plasma from younger mice, the older mice performed much better.
However, improvement in performance disappeared if the plasma was heated to a high temperature before being given to the mice. Heat can alter proteins, suggesting proteins in the young blood infused into the old mice could be responsible for the changes in their cognitive performance.
The team is now trying to discover what these proteins might be, and which tissues they come from.
Prof. Wyss-Coray is co-founder of Alkahest, a biotechnology company that is exploring the therapeutic potential of the study. He says they do not yet know if what they found will work in humans, but is hoping they can set up a trial sooner rather than later.
The US Department of Veteran Affairs, the California Institute for Regenerative Medicine and the National Institute of Aging helped fund the study.