Extending life and prolonging youth has long been a fascination of the scientific community, and blood has often had a starring role in related ideas and experiments. As far back as the 17th century, Royal Society founder Robert Boyle raised the idea of "replacing the blood of the old with the blood of the young".
Young blood as a fountain of youth has captured cultural imaginations throughout history, too, in our enduring fascination with vampire stories. Most recently, the billionaire biohackers of Silicon Valley are taking an interest in the area.
Tech investment magnate and Gawker nemesis Peter Thiel, for example, is keeping an eye on life-extension technologies. "I'm looking into parabiosis stuff, which I think is really interesting. This is where they did the young blood into older mice and they found that had a massive rejuvenating effect [sic]," he told Inc. magazine over the summer.
The billionaire biohackers of Silicon Valley are taking an interest in blood
Cue a flurry of excited headlines around the idea that a blood transfusion could conquer death. While interpretations were often simplified and no, young blood can't make you live forever, there has been a number of findings over the last decade around the power of blood that have significant implications for human health and the ageing process.
Parabiosis itself is a somewhat macabre technique that was pioneered in the 1800s and revived at various times since. It involves surgically attaching two animals – usually mice – together to create a shared circulation system. Heterochronic parabiosis is when one mouse is young and one is old. Once the blood vessels are joined, blood can be mixed between the young and old partner.
Experiments in the 1950s suggested blood may hold the key to reversing ageing but the practice of parabiosis was largely ignored until the last decade. It was resurrected again as scientists learned more about stem cells and how they function. Alongside knowledge gleaned from new areas of molecular biology and genomics, the time was right for a return to parabiosis to explore key questions about ageing and regeneration.
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While working as a PhD student in the lab of Tony Wyss-Coray, neuroscientist Saul Villeda wanted to see if blood could affect the brain. In particular, whether young mouse blood could rejuvenate neural stem cell function, synaptic plasticity and cognitive function in an old mouse brain.
"At the time that seemed almost counterintuitive," he said. "There's a blood-brain barrier – how could blood be influencing something like cognition? But it was an interesting question to pursue."
At first, Villeda used parabiosis, stitching together mice for a few weeks. It sounds gruesome but scientists use the technique because it requires far fewer animals than other processes. "Of course from a translational perspective, injection is the way to go," he noted, shutting down the image of Keith Richards spending his weekends stitched up to youngsters.
The experiment showed that the young blood was affecting the brains of the older mice. Old mice that received young blood had an increase in neurons and a burst of activity in the hippocampus, the area of the brain responsible for memory. In tests, the old mice had better memories and cognitive function. Not only that, the older animals looked healthier and their hair was smoother. "They just looked better," said Villeda. When the experiment was reversed, the young mice with the old blood slowed down and their cognitive function worsened.
Parabiosis involves surgically attaching two animals together to create a shared circulation system
The results were unexpected. Villeda would not have bet on learning and memory being restored. The mice that were 18 to 19 months old were the equivalent of a human in their mid-60s. "That's taking a neuron that's been there for decades and there's a possibility of making it come back structurally, molecularly, functionally. That means ageing is not final. That means there are ways we can tweak ageing to reverse some of it and we can have effects on learning and memory. To me, that was wild."
So does that mean ageing might not be final in humans? "That's the assumption," said Villeda. "There's evidence that it gets tougher as you get into complex organisms but there's an underlying truth that we can do something to ageing, that it's malleable. I think that will translate all the way to us to some level."
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As well as cognition and memory, young blood has also been found to rejuvenate bone, muscle, liver, pancreas and myelination in the spinal cord through studies by other scientists.
Professor Robin Franklin at the University of Cambridge led a study that showed that young blood could promote regeneration of lost myelin sheaths in older mice, the tissue that is lost in multiple sclerosis. He set out to answer two specific and related questions: could the ageing stem cell be made to work like a young stem cell? And are the changes that occur in brain stem cells reversible or irreversible?
"What was rather dramatic about our experiment and has been repeated in other adult tissues – skeletal muscle, cardiac muscle – was that it turns out that actually you can make ageing stem cells regenerate as if they are young stem cells if you give them a young environment," he said.
The model suggested the tricky technique of parabiosis might not be needed at all; instead, a drug could be used to change the environment of an old stem cell and improve its function. As MS patients age, they are more in need of regeneration therapy. Franklin's work showed that the therapy could be drug-based, to galvanise the aged cells already in the brain, which is a more attractive and less risky therapy than injecting or transplanting cells.
Villeda's work showed something similar. After using parabiosis, Villeda injected just plasma into the mice and found it had the same effect. "Studies shown can recapitulate a lot of the aspects of parabiosis just by injecting the plasma. We know it's some sort of soluble factor or factors in there. You don't need the sewing part, you just need the introduction."
Franklin's lab is currently studying how stem cells become myelinating cells with the hope of designing new drugs. "The notion of drug-based regenerative medicine for MS is already in the clinic and on the brink of becoming a reality," he says.
It is early days in the field and there are obstacles to overcome and questions to be answered. "I believe there's not enough young blood in the world to treat every Alzheimer's patient so we're seeing limitations," says Villeda. "We're still figuring things out. That's where preclinical trials come in."
One thing we can't do is bring back the dead
Clinical human trials are under way. A startup called Alkahest working out of Stanford University is looking at the effect of young plasma on Alzheimer's patients. Another, called Ambrosia, is charging people $8,000 for transfusions of plasma from donors less than 25 years old for those over 35. Villeda is skeptical about the age range. It's not entirely clear when young blood stops being 'good' and bad blood starts being 'bad'.
Also, doubts remain about how effective or limited the therapy could even be for humans. "I'm super excited but I think people are trying to jump the gun, especially here in the Silicon Valley," says Villeda. "I feel for patients who email me that I don't know. I want to tell them there's hope and we have some really exciting science but you're going to have to give us a little bit of time."
But serious scientific questions about the process of ageing are certainly being answered. "One thing we can't do is bring back the dead," says Villeda. "If you get to the stage that disease is so far along that cells are dying, that's beyond the ability. But prior to that, blood could have a benefit to most of the degenerative diseases."
As people live longer and ageing better becomes more of a priority – the number of people with dementia in Britain is predicted to increase to more than one million by 2025 – this research couldn't be happening at a better time.