Young Blood, Old Monsters and Rejuvenated Rodents
Author: Patrick Wilson
This essay was originally posted on the Staying Alive (Path findings) Substack.
Imagine a future in which affluent older people can reverse the ageing process through regular transfusions or injections of youthful blood plasma. In Andrew Barrer’s 2020 Young Blood trilogy, a corporation sets up idyllic ‘farms’ offering a life of hedonistic bliss for aimless post-millennials. They also get their student loans paid off in return for having their blood harvested.
But perhaps that future is already here, or at least in Monterey, California. In August 2017, the world’s press enjoyed a feeding frenzy over the launch of a new ‘trial’ of blood plasma transfusions, as The Guardian reported:
“Ambrosia, the vampiric startup concerned, is run by a 32-year-old doctor called Jesse Karmazin, who bills $8,000 (£6,200) a pop for participation in what he has dubbed a “study”. So far, he has 600 clients, with a median age of 60. The blood is collected from local blood banks, then separated and combined – it takes multiple donors to make one package.
The satirical sitcom Silicon Valley featured a tech guru who kept a teenage ‘blood boy’ for regular transfusions. This character was supposedly based on PayPal billionaire Peter Thiel, who was in turn rumoured, possibly by Karmazin himself to drum up business, to be spending thousands on treatment.
Meanwhile in the grey havens of Florida, Dr Maharaj, a physician specialising in traditional and ‘alternative’ anti-ageing treatments, was reportedly promoting a scheme charging participants $285,000 per person for a series of transfusions. The normally sober BBC raved: “…the super-wealthy are now pumping themselves with the blood of young people in an attempt to prevent themselves from ageing.”
So is the vampire, our old foe and seducer, now alive and sucking? While legends of undead blood-feeders are found in folklore worldwide, they took their modern literary and aristocratic turn two centuries ago with a truly Byronic tale.
It was a dark and stormy night…
…in June 1816, the ‘year without summer’, when the eruption of Mount Tambora cast its gothic pall over the globe, bringing worldwide crop failure and famine. Lord Byron, on the run from his scandalous affairs in England, was holed up in a rented villa on Lake Geneva with like-minded libertines Percy Shelley, Mary Godwin, Claire Clairmont and the brilliant but socially awkward 20 year-old Dr John Polidori, his personal physician.
High on laudanum and readings of Fantasmagoriana, the young literati held a ghost story contest, that famously unleashed Mary’s Frankenstein: The Modern Prometheus on an unsuspecting world, giving birth to modern horror and sci-fi. Byron himself improvised a story about the gruesome death of a dissolute aristocrat. Inspired by this tale, and by the character of Byron himself, Polidori later wrote a novella about a mysterious monstrous English Earl, travelling around Europe and returning from the grave to seduce young women and tear their throats out in gruesome fashion.
Published in 1819, The Vampyre was a sensation, not least because Polidori published it as "A Tale by Lord Byron", who promptly denied it. Finished as a physician, poor Polidori received scant acclaim or profit as an author; afflicted by depression and gambling debts, he died just two years later at 26. Meanwhile, his creation The Vampyre had ignited a craze across Europe, spawning translations, imitations, dramatic plays, operas. It was the inspration for later gothic romances like Bram Stoker’s Dracula and much of the genre we now call horror.
Some of these stories took a scientific turn. In Mary Elizabeth Braddon's 1869 novel Good Lady Ducayne , the eponymous aristocrat 'born the day Louis XVI was guillotined' employs a progressive doctor, who transfuses blood from a series of young female paid companions to keep her in wonderfully wicked health over the years. Tragically, the girls all sicken and die, suggesting either his methods or their immune systems are compromised.
So is Dr Karmazin the latest antihero in this scandalous tradition? Ambrosia suspended its ‘trial’ in 2019 after the US Food and Drug Administration (FDA) issued a statement that:
"simply put, we’re concerned that some patients are being preyed upon by unscrupulous actors touting treatments of plasma from young donors as cures and remedies. Such treatments have no proven clinical benefits for the uses for which these clinics are advertising them and are potentially harmful. There are reports of bad actors charging thousands of dollars for infusions that are unproven and not guided by evidence from adequate and well-controlled trials.”
Aptly, after spending several months reassessing the rules, the company rose from its coffin, deciding their service was technically legal. Karmazin launched Ivy Plasma, a new therapy venture offering off-label transfusions from donors who aren’t exclusively young. As The Huffington Post reported:
“Our deep dive into Ambrosia outlined a laundry list of issues: its secretive purchase of plasma from a blood bank that recruited teenage donors for “saving lives”; Karmazin’s mysterious agreement with authorities to stop practicing medicine in Massachusetts; turmoil among the small circle of people who worked for Ambrosia; Karmazin’s repeated refusal to release the results of Ambrosia’s controversial pay-to-participate clinical trial; and his many wild, scientifically unsupported claims about his treatment’s alleged benefits (including age reversal and near-immortality) for people suffering from a variety of ailments.”
There was also the small matter of Karmazin’s having lied about a 65-year old participant who died after taking transfusions, claiming he was in fact alive, and then when the Post revealed a copy of the death certificate, that he had faked his own death for personal reasons.
“Although he has been unsuccessful as a doctor and an entrepreneur, Karmazin is a master at twisting narratives and bending the truth.”
In true Byronic style, the results of his ongoing ‘trials’ remain shrouded in mystery. This is not entirely surprising, as without a control group to compare with, it is difficult to discern any effects the transfusions may have. This problem is inherent in ‘paid trial’ model; after all, would you pay $8,000 a shot for a 50% chance of getting a plasma placebo?
The nexus of blood and cash makes great stories, but despite the drama and deception, blood transfusion is a well-tested and generally safe procedure. There is now a wealth of evidence that there is something in young blood can help slow and even reverse the effects of ageing, at least in rodents.
This is a fascinating area of research that might soon bring great therapeutic benefits, but it also involves animal experiments that would not be out of place in a Victorian horror novel. Dear reader, if you are anti-vivisection or of a sensitive disposition, feel free to skip the gory detail and cut to the bloody climax…
Of mice and monsters
Evoking echoes of Frankenstein, ‘heterochronic parabiosis’ is the technical term for the gothic procedure by which older organisms can be rejuvenated by physically connecting their circulatory systems to younger individuals of the same species. Parabiosis, which just means ‘living together’, occurs naturally in plants and fungi, and in animals as conjoined twins.
As an experimental technique, it was pioneered by French physiologist Paul Bert, who won an Academy prize in 1866 for surgically sewing together the blood vessels of a pair of rats. He injected one rat with belladonna, the active ingredient of deadly nightshade, and soon after the pupils of both animals dilated, demonstrating that they shared a circulatory system. Over the 150 years since, parabiosis studies have led to advances in our understanding of hormones, the immune system, and cancers.
‘Heterochronic’ refers to the conjoining of older and younger animals. In the 1950s Clive McCay, the veteran professor of animal husbandry at Cornell University, and his team sewed 69 pairs of rats into parabiosis. Many of these pairs died quickly, probably due to infection, but others survived for many months, and though the results were inconclusive, there was some evidence that bone density of the older rats improved.
Several decades earlier, McCay had pioneered the study of nutrition and ageing. He demonstrated that dietary restriction increases the lifespans of rats, and also helped develop healthy rations for the US forces in World War II. Cutting calories has since been shown to extend healthy lifespans, sometimes radically, in many animals including humans. This is also a fast-developing field of research, but rather than take a dietary diversion, let’s save the guts for later and go with the blood flow.
McCay’s parabiosis experiments were rather primitive and poorly controlled, but follow-up work in the 1970s showed that the circulation of blood from young mice increased both the longevity and the tissue function of older mice. After a 30-year hiatus, this work was picked up again at the dawn of the new millennium by the conjugally conjoined couple Irina and Michael Conboy and their team at UC Berkeley. They tested how well muscle, liver and brain tissues healed in various combinations of conjoined mice.
Their results were dramatic: old mice attached to young mice healed as well as young mice attached to other young mice. Using genetically engineered young mice with green glowing cells, they proved that this effect must be caused by some factor in the blood of the younger mice that reactivated the clapped-out stem cells of their older partners, rather than youthful cells themselves transported into the older mice.
They also did in vitro experiments, bathing older mouse cells in young blood plasma, which restored the cells to their youthful state, creating a media splash when their work was published in 2005. However, the true picture, like the blood, turned out to be mixed. The younger mice were clearly disadvantaged by their parabiotic partners, and when the team tried injecting youthful plasma into old mice, the benefits were less clear than those achieved by parabiosis.
While no one has yet tried parabiosis on humans (if anyone has, they have not admitted it), several safer and more ethically sound trials in which people are injected with young plasma are yet to report any positive results. For example, a US trial in Alzheimer’s patients didn’t succeed in slowing the disease. The research in humans to date has also been complicated by lack of consistency about the transfusion products used in trials, which makes comparison difficult. It is clear that a simple infusion of young blood is no silver bullet.
Extracellular vesicles: elixirs of youth?
So is there some secret ingredient in young blood that can help delay or reverse ageing? Or alternatively, does older animals’ blood contain something that degrades their cells’ ability to regenerate and repair? The answer from the Conboys and other researchers is, as usual in science, ‘it’s complicated’!
Just across the bay at Stanford, Tony Wyss-Coray and his team have been working over the past decade to identify the factors in young blood that are responsible for the rejuvenating effect in older mice, and those in old blood that cause age-related degeneration. Their results suggest that it is a complex signalling environment, and that many molecules and metabolic processes are involved.
Promising candidates for therapeutic interventions include oxytocin, the ‘love hormone’ that plays a complex role in signalling and is known to decline with age. Combined with already approved drugs called ALK-5 inhibitors, which effectively ‘reawaken’ stem cells in the tissues of mice and humans, injections of oxytocin in mice appear to promote regeneration of brain, muscle and liver.
More recent research has examined the role of extracellular vesicles (EVs), tiny bubbles containing micro-RNA and proteins released from stem cells that appear to have a key role in signalling. They can switch genes in their target cells on or off, thus changing the behaviour of the cells.
In March 2022, New Scientist reported the findings of Consuelo Borrás at the University of Valencia in Spain, on a five-year study of the role of extracellular vesicles on ageing in mice. When Prof. Borrás injected small EVs from stem cells derived from the fat tissues of young mice into old mice, the effects were dramatic. Within a few weeks, the mice appeared younger and stronger. Two control groups of old mice showed no such rejuvenation; one was given only saline injections, and the other was injected with EVs from other old mice.
The treated rodents not only demonstrated enhanced muscle strength and improved coordination and endurance across a range of tests, but they had also grown lustrous new fur. The researchers plucked small patches of the mice’s skins bare just before injection; after two weeks, the hair had completely regrown in the mice given the EVs, but only partially in the controls.
However, the rejuvenation turned out to be temporary: two months after the injections, the effects had faded, and the mice reverted to their feeble old selves. In April, Prof. Borrás kindly agreed to speak with me, and with her permission, I quote excerpts from our correspondence.
“We started working on extracellular vesicles (EVs) in 2017 with the first experiments in vivo. I thought that stem cells exert some of their effects through the EVs, so maybe injecting EVs from young mice into old mice could benefit them. It is in principle a safe procedure; EVs don’t generate immune reactions in the host, and they are in general safer than stem cells.
“I was very surprised – we didn't expect to obtain such good results… the treatment was effective in all mice that we treated. We started with a very small number of animals, so until we repeated the experiment and increased the numbers we didn’t trust them!”
In September I happened to visit Valencia and interview Prof. Borras. Her team is now trying to identify the specific components within the EVs that may be responsible for these effects. She is also preparing experiments in humans: not injecting anything, but instead testing formulations of EVs in skin cream to apply to pressure sores in older patients. These lesions are essentially areas of skin tissue in which cellular signalling has broken down, partly due to ageing.
This progress is impressive, but Consuelo counsels caution:
“I think that these studies are important to find the factors that are responsible for the protective effect of the blood or other tissues from young animals, such as stem cells from adipose tissues, and use these factors to develop new drugs effective for age-associated diseases or for delaying the process of ageing.
“I think it opens new possibilities to treat age-associated diseases and delay the ageing process. However, we are a long way from translating these experiments to humans. The methodology is very complicated and the treatment needs to be repeated, so we need to investigate more and find which components are responsible.”
“I don’t think that “young blood” should be used directly in old individuals. Ageing is a very complex process… I don’t think you can do something for ageing with only one molecule or only one thing. There are likely to be several elements at least.”
The prospect of being able to slow or reverse the degeneration of our bodies associated with ageing has powerful appeal. It is natural for people, even those of us who are not ‘super-wealthy’ to wish for longer, healthier lives. If you are comfortably retired in Florida, the price of golf club fees might be a small one to pay for a treatment that offers the chance of a few more years. After all, there’s not much point being on the golf course if you’re too frail to hold a club.
Current advances in research in animals and humans are showing great promise, and are likely to bring therapeutic products within the next decade. We may look forward to safe, well-tested treatments for the diseases of ageing as they affect specific tissues.
Further ahead, we might envisage older people being given regular injections of factors that younger people that stimulate cellular repair and regeneration, and prevent defunct senescent cells from spreading signals that lead to inflammation and tissue damage. If the R&D is managed well, these should be widely available through the NHS and other health systems.
Of course blood studies are only one stream in the growing body of research in bio-gerontology, the science of the mechanisms of ageing. In future blog posts I will address other areas of research including nutrition, exercise and genomics.
The happy ending to this chapter, is that you won’t need to be a vampire, bio-hacker, tech billionaire or evil corporation to benefit from the revitalising molecules abundant in young blood. Thanks to these scientists and their experimental mice, we soon might all have access to life-extending and life-enhancing treatments.
About the Author
Patrick Wilson is Head of Global Health Communications & Stakeholder Engagement at the UK’s National Institute for Health and Care Research (NIHR) and has more than 20 years’ experience leading communications in universities, research institutes and NGOs focusing on science, health and international development.
He is passionate about helping people live longer and healthier lives, and is active in various science, technology, health and ‘rationalist/ish’ networks. He is writing a book on advances in ageing science, and recently started a blog - Staying Alive (Path findings) | Patrick | Substack.
He's a husband, dad of 3, samba drummer, dancer, football (soccer) coach and player, river swimmer, naturalist & junglist. Connect on (1) Patrick Wilson | LinkedIn
One point you missed is that the longevity benefits might be due to the removal of pathogens/negative factors, as opposed to the addition of positive factors. This means you could filter blood as opposed to requiring transfusions