It’s fitting that the world’s oldest surviving work of literature is about a man who wanted to do just that: live on. The Epic of Gilgamesh follows the eponymous hero, a king and mighty warrior powerful enough to slay monsters but nonetheless powerless to change his fate. Time will eventually wear him down, and he will die.
It’s futile to try and evade death — but that hasn’t stopped people from trying. Advances in medicine and food production, as well as a recent trend away from international wars, have led to an increase in average life expectancy for people in many parts of the world.
Yet while many populations today live longer than their ancestors did, death is only ever postponed, never vanquished. Even if someone survives infancy, avoids plagues and wars, and eats a diet optimally tuned to keep their body healthy, age will still wreak its havoc on the body, making flesh sag and organs fail. Time may spend decades drawing its bowstring, but its arrow never misses.
Recent studies suggest the human lifespan is approaching a limit, around 125 or so, past which bodies simply cannot function, no matter how healthy or careful a person may be. At the same time, there exists a school of thought that death is merely another disease — like polio or measles — and can therefore be eradicated.
There are a number of approaches to the problem of aging, but one that has gained a lot of attention lately is the study of blood, and how the blood of the young, injected into the veins of the old, can smooth over the rough work of time. The benefits — restoring functionality to muscles, organs, even mental faculties — are intriguing, but the method is disturbing to many.
“The first experiment, proving this worked was in 1954. It was a guy at Cornell, Professor McCay, and he did this,” says Jesse Karmazin, founder of a startup called Ambrosia, which studies the rejuvenative properties of blood. “He did this experiment in mice and it worked, and people did not like this idea. I think they just didn’t think this was appropriate, basically. It’s a tremendously old idea, and I think we’re just seeing the same thing happen again, where people disagree with the premise, and so they just say it shouldn’t happen.”
The research Ambrosia is doing could be a fatal blow to mankind’s oldest enemy, but it also occupies a precarious space in the public imagination — a space where concerns over ethics, classism, and common human decency intersect.
How does aging work?
A human lifespan, like a narrative, has an arc. A rising action, as one develops from frail infant to fully-formed adult, and an eventual decline, however long, on the way to a conclusion. Poets and philosophers alike have labored to express the pathos of — and find meaning in — the body’s inevitable decline. For researchers who would combat aging, settling on a definition of aging, and a cause, is essential; to treat a disease, you must understand it.
Professor Michael R. Rose, in Evolutionary Biology of Aging, defines aging as “a persistent decline in the age-specific fitness components of an organism due to internal physiological deterioration.” Put simply, parts of the body break down over time. It’s easy to identify what aging is, but rather difficult to explain why it happens.
The prevailing theory is that aging is a product of evolution: life’s engineer of happenstance. According to our understanding of evolution, organisms mate, and their traits are passed on to offspring through genes. Although pseudo-Darwinists often try to ascribe a narrative to evolution — such as that “survival of the fittest” attempts to weed out the “weak” — it’s a process governed by coincidence. Two organisms avoid predators and survive long enough to mate, and they pass on their genes, however admirable those genes may seem to a subjective, human observer. So it is that the lowly cockroach endures alongside the mighty lion.
From the view of many biologists, our bodies break down because evolution never granted us genes for extended life. As the New Yorker’s Tad Friend puts it, “The reigning view among longevity scientists is that aging is a product not of evolutionary intent, but of evolutionary neglect: we are designed to live long enough to pass on our genes, and what happens afterward doesn’t much matter.”
Time may spend decades drawing its bowstring, but its arrow never misses.
The physical mechanics of aging are complex, and researchers’ understanding of the process often shifts. One theory of aging focused on telomeres: repeated sequences of genetic data on the ends of chromosomes. When cells divide, the DNA within must be replicated, but the process results in chromosomes with small sections missing at the end. Telomeres, repeated sequences, sit at the end of a chromosome, so that when the cell divides, a complete chromosome is the end result.
The telomeres themselves suffer the shortening, however, and in most cells they do not replenish themselves. Eventually they wear away, and the cells follow after, turning senescent and ceasing to function. Some research indicates that telomeres correlate to aging, though whether the shortening causes aging is a matter of debate.
Another proposed cause of aging, and one which has become a popular topic of late, is pumping through your veins as you read this: blood.
The rise of parabiosis
Blood has always been a potent symbol of life — a passage from the Bible remarks that “the life of a creature is in the blood” — and there has been a persistent fascination the possibility that it might grant life. The Germanic hero Siegfried, having bathed in the blood of a dragon, became invincible in every spot the blood touched. In the wake of a series of a murders orchestrated by the Hungarian countess Elizabeth Bathory, folklore portrayed her as bathing in the blood of her victims in an attempt to stay young.
Belief in the rejuvenative power of blood may seem like the stuff of folklore, but researchers have found a remarkable amount of truth in the idea. These findings grew from the concept of parabiosis, in which two subjects are joined together physically, to study the effects on their bodies.
One of the earliest known examples of parabiosis came from a scientist named Paul Bert, who surgically joined rats in such a way that they shared a single circulatory system. Though his experiments may seem grotesque today, they won Bert an award for Experimental Physiology, and paved the way for modern research into the anti-aging properties of blood.
For over a decade now, studies about the role of blood in the aging process have become frequent, and increasingly high profile. Harvard scientist Amy Wagers experimented on mice, and observed that when the circulatory systems of young mice and old mice were joined together, the hearts of the older mice — grown swollen as a result of aging — shrank to a healthier size like that of the younger mice. In trying to determine the precise cause of the rejuvenation, Wagers’ team eliminated factors like blood pressure and behavioral changes, eventually zeroing in on a blood-borne cause, a particular protein known as GDF-11.
Another study, conducted by Stanford researchers including Tony Wyss-Coray, studied the effects of young blood on cognition. As Wyss-Coray explained in a TED Talk: “Could we potentially understand more about the brain at the molecular level if we see the brain as part of the entire body. So if the body ages or gets sick, does that affect the brain? And vice versa, as the brain gets older, does that influence the rest of the body? And what connects all the different tissues in the body is blood.”
The fascination among the rich and powerful with living forever, and the imagery…has given parabiosis research a bad reputation
As the body gets older, factors that help develop and maintain tissues decrease, while factors that cause inflammation increase. The researchers connected biologically aged mice to young ones. The older mice showed increased levels of neural stem cells. Curiously, no blood cells entered the brains, and so the researchers deduced that it must be plasma that carries the factors into the brain.
The mice performed better in in memory tests. The mice were trained in a Barnes maze, a flat surface with various holes in it, one of which conceals an escape tube. The mice are exposed to bright light, driving them to seek a dark place, and are trained to locate the escape hole by memorizing landmarks. Old mice injected with saline struggled to memorize the location of the escape tube, wandering from hole to hole, aimlessly. Meanwhile mice of the same age, treated with plasma from young humans, were able to remember and seek out the proper hole.
Research into the effects of young blood on old creatures has been inspiring, and it has sparked a particular fascination among the rich and powerful. Earlier this year, The New Yorker detailed a meeting of Silicon Valley investors, celebrities, and scientists who gathered in Los Angeles to discuss technologies that might extend the human lifespan. In episode of the popular TV show Silicon Valley, creator Mike Judge took a jab at parabiosis specifically with a scene that depicted a wealthy entrepreneur who paid a young man to function as his “blood boy.”
The fascination among the rich and powerful with living forever, and the imagery of blood flowing from young bodies to old — a sort of techno-vampirism — has given parabiosis research a bad reputation, and Karmazin is well aware of it.
“…there’s lots of people who don’t think blood should be used in this way,” he said. “Coming from a medical background, it’s such a ubiquitous [criticism].” The problem, according to Karmazin, is a lack of understanding among the public. While parabiosis experiments in mice often involve stitching two specimens together, treatment in humans is far less gruesome, and can be performed through a simple blood transfusion.
“There’s like ten million transfusions each year in the U.S. It actually is an extremely common and extremely safe procedure,” Karmazin adds.
One could argue that even though Ambrosia’s research is safe, it might constitute a waste of resources, given that “Approximately 36,000 units of red blood cells are needed every day in the U.S.,” according to the Red Cross.
Karmazin emphasizes, however, that Ambrosia’s treatment doesn’t actually use blood, but rather, like Stanford’s experiment, plasma — the solution in which red and white blood cells are suspended. As he explains, “when people donate blood, the red blood cells, they spin them out of the plasma, and then they discard the plasma, essentially. Sometimes it gets sold, and people make drugs out of it, but a lot of times it just expires, there’s no use for it. We’ve essentially been throwing away all this young plasma since blood banks were invented.” From Ambrosia’s perspective, the research utilizes a resource that often would not help people anyway.
If parabiosis lives up to its promise, concerns about resource allocation may fall by the wayside. Although society may look at the reversal of aging — or at least its effects on the body — as a frivolous indulgence for the rich and powerful, the health benefits appear tremendous. Aging’s effects are more than skin-deep; the aging process grinds away at organs, leading to disease. As researchers like Wagers and Wyss-Coray have demonstrated through their work, reversing the effects of aging can restore mental faculties and organ functions.
Among Ambrosia’s targets are diseases like diabetes and Alzheimer’s, which afflict millions of Americans. “We’ve treated Alzheimer’s patients and had remarkable improvements,” Karmazin says.
The possibilities are exciting, and Karmazin drifts into speculation. “It looks like there’s no theoretical limit,” he speculates. “You could simply march back someone’s appearance and health as far as you want, to the point of being a teenager, although I would expect it to be diminishing returns. The biggest differences probably happen at the beginning, and then it probably gets slower and slower, but maybe not.”
Ambrosia’s study is not without flaws. The most noteworthy is that the study lacks a control group. An essential part of many experiments, control groups help researchers to identify intervening variables. In the case of a medical study like this, for example, scientists might give one group the actual treatment while giving another group a placebo, to test if the young blood is actually what causes changes in subjects.
Karmazin admits the design is not perfect, but argues that it’s a necessary compromise. “If we had a control group, most people wouldn’t be signing up. It would take even longer, or maybe it wouldn’t even happen at all, that we would learn about how this treatment helps people,” he explains. “And it doesn’t make the study of zero value, it just means it’s less informative than a placebo-controlled study.” Ambrosia was able to secure FDA approval for the study, despite its flaws., a point Karmazin emphasizes. However insidious the research may appear to mainstream observers, it has the government’s seal of approval.
Just how effective has Ambrosia’s treatment been? It’s too early for the company to make any definitive claims, Karmazin tells us. At the time we spoke, the study included 100 or so people; Karmazin hopes to expand to at least two or three hundred (still small, for a medical study) before he considers publishing results. He was, however, able to offer at least a hint as to what he had seen so far: “I think the results from even a single dose are long lasting. That’s essentially what I’m allowed to say at this point.”
For now, parabiosis remains a fringe topic, largely brought up for its controversial aspects. The research will continue, however; if the results are positive, humanity could see a future without aging, although it remains in question who would be able to reap those benefits.