Rando and Wyss-Coray were deluged with phone calls from reporters and from the general public—some of them dubious, not to mention scary. There were reports of rich old men—and, yes, it usually seems to be men—procuring a ready supply of young blood to prolong their lives.
The scientists involved were more circumspect. In a 2013 journal article, the Conboys and Rando pointed out that even in highly inbred strains of mice and rats, the risk of parabiotic disease was as high as 20–30 per cent. Moreover, it was not obvious whether all of the positive effects of parabiosis could be attributed to the blood; the older animal would have also benefited from the better-functioning organs of the younger partner, such as its liver and kidneys. To test this, the Conboys conducted a study in which they exchanged blood between two animals that were not joined. They found that the adverse effects of old blood were more pronounced than the beneficial effects of young blood.
Such cautionary views did not stop lots of companies from trying to capitalize on the hype, rushing ahead before any careful human trials were completed. One company, Ambrosia, offered blood plasma from donors aged sixteen to twenty-five for $8,000 a liter. Alarmed, the US Food and Drug Administration (FDA) issued a warning that these treatments were unproven and should not be assumed to be safe, and strongly discouraged consumers from pursuing this therapy outside of clinical trials with appropriate regulatory oversight. In response, Ambrosia stopped offering the treatment, but only briefly: the people involved soon began marketing it again under the aegis of a new but short-lived business named Ivy Plasma—before returning to its original name. Ambrosia’s CEO, Jesse Karmazin, said, ‘Our patients really want the treatment. The treatment is available now. Trials are very expensive, and they take a really long time.’ Most serious scientists, including those who pioneered the discoveries, believe it is premature and potentially dangerous to offer these kinds of treatments to humans without proper clinical trials.
Beyond all the hype, Thomas Rando’s initial findings set off an extensive search for specific protein factors in blood that could be related to aging. In theory, you could have factors in young blood that stimulate growth and improve function; by the same token, old blood might contain factors that made things worse. Wyss-Coray and his colleagues showed that it was both. As they described in a 2017 article in the journal Nature, proteins from umbilical cord plasma revitalized the function of the hippocampus—a part of the brain crucial for the formation of both episodic and spatial memory. As for old blood, they zeroed in on a protein that impaired hippocampus activity; blocking it relieved some of the adverse effects.
Of course, in the parabiosis experiments, young blood improved many organs, not just the brain. Amy Wagers of Harvard University, who was a member of Rando’s original team at Stanford, screened the hundreds of protein factors in blood to pinpoint the ones more prevalent in old or young blood. A factor called GDF11 was abundant in young mice but not in old, and it could rejuvenate heart tissue. But it didn’t just act on heart tissue. She and her colleagues showed that the factor reversed age-related deterioration of muscle tissue by reviving stem cells in old muscles and making them stronger. In a second study with her Harvard colleague Lee Rubin, they showed that it spurred the growth of blood vessels and olfactory neurons in the brain.
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Stem cells can decline in number and lose function with age, and clearly some of the factors in blood work by reactivating them. But what about the old blood making the young mice worse off? A recent study by the Conboys and Judith Campisi, another leading aging researcher, showed that treating young mice with old blood quickly increased the number of senescent cells in their circulation. This means that senescence is not just a response to stress and damage from the environment, nor is it something that simply happens over time. It can also be induced rapidly. Clearing those senescent cells reversed some of the harmful effects of old blood on multiple tissues.
Blood need not even be from young animals to confer benefits. Exercise has a real benefit on many aspects of our metabolism, including insulin sensitivity and mitochondrial biology. It turns out that blood from adult mice that had been subjected to an exercise program can improve cognitive function and regeneration of neuronal tissue. Rando and WyssCoray showed that exercised blood can also rejuvenate muscle stem cells.
Using a new way of measuring effect based on which mRNAs are made in different tissues, they showed that young blood and exercised blood act in different ways. Parabiosis from young animals reduced the activity of genes that caused inflammation, whereas exercise increased the activity of genes that decline with age. Although they both stimulated growth of brain tissue, each stimulated different types of cells.
Identifying aging factors in blood and understanding how they work is now a major area of research. Scientists hope that one day it might be possible to administer a cocktail of a few factors with real anti-aging effects. This hope is spurring not only basic research but also has resulted in the creation of many biotech companies, including ones founded by some of the pioneers in the field.
While science is advancing to find out precisely which combination of blood factors is most beneficial, some billionaires are unwilling to wait. They continue to be drawn to the Dracula-like allure of young blood. For instance, Bryan Johnson, the middle-aged tech mogul behind the company Braintree Payment Solutions, spends $2 million a year on his anti-aging regimen, which includes two dozen supplements, a strict vegan diet, and, as befits a techie, lots of data, including more than 33,000 images of his bowels.
This excerpt from ‘A Touch of Genius’, edited by Rudrangshu Mukherjee, has been published with permission from Aleph Book Company.