Nobody wants to get old. Or no one wants to experience the slow decline of physical and mental capacities associated with aging. Billionaire venture capitalist Peter Thiel has expressed his reluctance to age quite vocally. He has also put his money where is mouth is by investing in startups that take anti-aging technologies from extreme basic research to potential therapies.
The most notorious of these ideas is parabiosis. In Thiel’s case, he means transfusing blood plasma from the young in order to fight aging. It sounds more vampiric than it is—no one is talking about drinking it. But early studies in mice have shown that there maybe some promise. There is some evidence that blood from young mice contain protein messengers that ramp up innate cellular repair and regeneration capacities in older mice.
New data presented at Society for Neuroscience meeting in November took the research to the next level. Researchers took blood from young human adults and transfused that into aging mice. Their memories improved. That was likely because some component of the transfused blood stimulated replication of neural stem cells in the hippocampus, the brains memory center. Neural stem cells decline significantly with age.
The idea of parabiosis has been around for more than 150 years. First experiments were done by surgically grafting the circulatory systems of a young mouse and an old mouse. The old mice would start doing better and the young mice would begin prematurely aging. Effects of parabiosis have been documented in many different organs. But scientists realized they could get the same results more simply by transfusing blood, specifically plasma. Megan Sculldelari at Nature explains the procedure:
By joining the circulatory system of an old mouse to that of a young mouse, scientists have produced some remarkable results. In the heart, brain, muscles and almost every other tissue examined, the blood of young mice seems to bring new life to ageing organs, making old mice stronger, smarter and healthier. It even makes their fur shinier. Now these labs have begun to identify the components of young blood that are responsible for these changes.
If this research holds up and plasma from young people becomes an anti-aging treatment, blood transfusions on a mass scale would be difficult to pull off. So the search for the active-ingredients in plasma is aggressively underway. It seemed early on that one protein, growth differentiation factor (GDF)11 and its cousin GDF 8, might be the important component. From Helen Thompson at New Scientist:
In both mice and humans, GDF11 falls with age. We don’t know why it declines, but we know it is involved in several mechanisms that control growth. It is also thought to mediate some age-related effects on the brain, in part by activation of another protein that is involved in neuronal growth and long-term memory. So the billion-dollar question is: would a GDF11 boost have the same effect in humans?
But researchers seem to agree that there are likely many active ingredients. Subsequent research has gone back and forth about whether GDF-11 declines naturally with age and whether it causes tissue regeneration and repair on its own. And it’s unknown if the effect is transient, meaning you’d need continuous transfusions to have the same effect.
Some human studies are underway. One study is giving older adults with Alzheimers disease transfusions of blood from younger people. It’s run by a startup called Alkahest, founded by one of the scientists who published results in mice. The other, run by a startup called Ambrosia is more controversial, according to Science:
The firm’s co-founder and trial principal investigator is a 31-year-old physician named Jesse Karmazin. His company, Ambrosia in Monterey, California, plans to charge participants $8000 for lab tests and a one-time treatment with young plasma. The volunteers don’t have to be sick or even particularly aged—the trial is open to anyone 35 and older. Karmazin notes that the study passed ethical review and argues that it’s not that unusual to charge people to participate in clinical trials.
There is high potential for side effects, as well. When cells grow and divide unchecked they can create cancers:
There are also lingering concerns as to whether activating stem cells — which is what the young blood most often seems to do — over a long period of time would result in too much cell division. “My suspicion is that chronic treatments with anything — plasma, drugs — that rejuvenate cells in old animals is going to lead to an increase in cancer,” says [Thomas] Rando, a Stanford neurologist. “Even if we learn how to make cells young, it’s something we’ll want to do judiciously.”
Another side effect, seen in mouse studies, is ‘parabiosis disease’ a form of rejection that occurs despite blood type matching. In experiments, researchers use genetically engineered mice to get around this problem, but that would not be possible for humans.
And there are many ethical implications. Where do we get this surplus blood from? Steven Novella at Science Based Medicine paints a dim picture:
The article focuses on how billionaire Peter Thiel is interested in plasma transfusions from young donors as a life extension and rejuvenation treatment, based on the science of parabiosis. I can’t help but also see the supervillain angle to this story – an aging billionaire, desperate to live forever, is feeding off the blood of young healthy victims. Of course, to get the full effect, a simple transfusion will not do. He will have to connect their circulatory system to his own.
Even the way we talk about this line of research is telling. Although it’s largely framed as what young blood can do to help aging, let’s not forget all those young mice who prematurely aged during the experiments. Parabiosis research may have as more to tell us about aging than how to artificially stay young. We can already gentetically engineer mice to model human diseases of aging. Adding that to parabiosis research could provide a lot of information about how aging and genetic risk for disease interact. In terms of basic research, parabiosis might be on track for a revival, a group of parabiosis scientists wrote in a Swiss medical journal:
Parabiosis and heterochronic parabiosis in particular could help answering some of the fundamental questions in this regard: are circulatory factors or cells in a young organism protecting against age-related disease, and vice versa, are factors or cells in the old organism predisposing or promoting disease in a younger organism?
Meredith Knight is a frequent contributor to the Genetic Literacy Project and a freelance science and health writer based in Austin, Texas. Follow her @meremereknight