Blood from young mice improved learning and memory in older mice, and increased connections between their brain cells
It is rumoured that the late Kim Jong-il would inject himself with blood from healthy young virgins in a bid to slow the ageing process. Remarkably, the North Korean dictator might have been onto something. Experiments on mice have shown that it is possible to rejuvenate the brains of old animals by injecting them with blood from the young.
Saul Villeda of Stanford University, who led the work, found that blood from young mice reversed some of the effects of ageing in the older mice, improving learning and memory to a level comparable with much younger animals. He said that the technique could one day help people stave off the worst effects of ageing, including conditions such as Alzheimer's.
"Do I think that giving young blood could have an effect on a human? I'm thinking more and more that it might," said Villeda. "I did not, for sure, three years ago."
Villeda connected the circulatory systems of an old and young mouse so that their blood could mingle. This is a well-established technique used by scientists to study the immune system called heterochronic parabiosis. When he examined the old mouse after several days, he found several clear signs that the ageing process had slowed down.
The number of stem cells in the brain, for example, had increased. More important, he found a 20% increase in connections between brain cells. "One of the main things that changes with ageing are these connections, there are a lot less of them as we get older," said Villeda. "That is thought to underlie memory impairment – if you have less connections, neurons aren't communicating, all of a sudden you have [problems] in learning and memory."
The work builds on a paper published last year in Nature where Villeda and his colleagues at the Stanford University School of Medicine found that the brains of young mice began to age more rapidly when exposed to blood from an older mouse. The number of stem cells in the older mice's brains also increased after receiving blood from the younger mice.
In the latest study, which has not yet been published in a peer-reviewed journal, Villeda also tested the behaviour of the rejuvenated mice. He took blood plasma – the fluid portion of blood that is not cells – from two-month-old mice and injected small amounts, around 5% of the total amount of blood in a mouse by volume, into 18-month-old animals eight times over the course of a month.
When he put the animals into a water maze, a test where they have to remember the location of a hidden platform, he found that the older mice did almost as well as mice of 4-6 months old. Untreated older mice would make many errors and swim down blind alleys in their attempts to find the hidden platform, whereas the mice that had received plasma from young mice located the platform first time, in most cases.
Villeda said that the young blood most likely reversed ageing by topping up levels of key chemical factors that tend to decline in the blood as animals age. Reintroduce these and "all of a sudden you have all of these plasticity and learning and memory-related genes that are coming back". Which factors in particular are causing the effect is unclear since there are hundreds of thousands in blood.
Turning the idea into a therapy for humans will take much more research, but Villeda said there was no reason not to think that, at some point in the future, people in their 40s or 50s could take therapies based on the rejuvenating chemical factors in younger people's blood, as a preventative against the degenerative effects of ageing.
Andrew Randall, a professor in applied neurophysiology at Exeter and Bristol Universities, said that the brain and other organs inevitably deteriorate as part of the ageing process. "Although this [research] may suggest that Bram Stoker had ideas way ahead of his time, temporarily plumbing teenagers' blood supplies into those of their great-grandparents does not seem a particularly feasible future therapy for cognitive decline in ageing. Instead this fascinating work suggests there may be significant benefit in working out what the 'good stuff' is in the high octane young blood, so that we can provide just those key components to the elderly."
Chris Mason, professor of regenerative medicine bioprocessing at University College London, said that real scientific breakthroughs "are often the result of an astonishing observation that if robustly examined may occasionally contain a nugget of great value. This may be one such occasion. The important questions are: what is in the blood of the younger mice that impacts the ageing process, and is it applicable to humans? Neither will be easy questions to answer."
He added: "Even if the finding leads only to a drug that prevents, rather than reverses the normal effects of ageing on the brain, the impact upon future generations will be substantial – potentially outweighing other wonder drugs such as penicillin."