It is years since Libavius proposed that young blood could rejuvenate older people. At the time, the idea was radical and dangerous. Even though modern science has made blood transfusions safe, blood remains a mysterious fluid: Wyss-Coray suspects that among them are factors that orchestrate the ageing process. If scientists can understand how they work, the ageing process might be laid bare. It could be slowed down, or perhaps even reversed.
When Wyss-Coray was in his 20s and 30s, he did not much care about ageing. Sitting in his office at the Veterans Affairs hospital, surrounded by books on immunology and biology, Wyss-Coray was fashionably unshaven, with a crop of blonde hair and lively blue eyes framed by dark rimmed glasses.
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And now it happens to me. It annoys the crap out of me. For Wyss-Coray, ageing has become much more than a personal bugbear. In , the prestigious US journal, Science, named his work on young blood one of its breakthroughs of the year. Another question also crops up: Wyss-Coray was the first in his family to go to university.
From the start, he set his sights on a career in the US. This kind of experimentation has major limitations. For humans, however, nothing so far has worked. Frustrated by the limitations of his experiments, Wyss-Coray looked for better ways to understand how the disease first arose in humans. Brain scans and cognitive tests were out — neither revealed anything about disease at the molecular level. Nor would it make sense to study the brains of the dead, as scientists had traditionally done: Wyss-Coray wondered if blood might hold the answer.
Human blood travels 96, kilometres along the arteries, veins and capillaries of the circulatory system. It circulates through every organ. What if blood picked up information as it streamed around the body? What if its molecular makeup reflected the state of the brain, as it aged and changed with disease? He assembled an international team of two dozen scientists to test the idea. The findings, published in , made headlines around the world.
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Wyss-Coray set up Satoris, a private company, to commercialise the research. The study was too good to be true. In the course of this work, however, he had come across something intriguing. He noticed that in healthy people, the levels of certain proteins in blood fell with age. By 20 years old, most had already dropped steeply.
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Meanwhile, the levels of other proteins ramped up. Some doubled or tripled in old age. What the changes meant, no one knew. On his desk sits a small display of chemistry lab glassware and dozens of miniature figurines of the New York Giants. It was Rando who hired Wyss-Coray in The question Rando wanted to investigate centred on stem cells. Rando wondered whether stem cells failed in old animals because they no longer got the right signals.
What if something in young blood turned them back on again? Perhaps he could make older people heal as fast as young ones. This procedure, pioneered by the 19th-century French physiologist Paul Bert, is known as parabiosis. For a long time, experiments involving parabiosis were gruesome. Not knowing what to make of their findings, researchers moved on to other projects.
Only when parabiosis was resurrected at Stanford did scientists start to make sense of the anti-ageing effects. Parabiosis is different today: The animals are genetically matched, so there is no risk of immune rejection. Once they have recovered from the operation, paired animals tend to eat normally and to make nests together. But the procedure is still disturbing — it would be a stretch to call the animals happy.
The young blood activated stem cells in the old mice that swiftly regenerated their damaged muscles. The young mice, however, fared worse for their exposure to old blood. Their stem cells became sluggish, and their tissues healed more slowly.
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Rando saw hints of another effect too, but needed more evidence before he could publish: The results led Wyss-Coray and Rando to collaborate. The kinds of proteins Wyss-Coray had seen rise and fall in blood were known to have effects on biological processes. What if they had driven the changes Rando had seen in muscle? Might they similarly revitalise the brain? Rather than being mere signatures of age, the proteins might be chemical cues for the ageing process itself.
Villeda grew up in Pasadena on the outskirts of Los Angeles. His parents had immigrated illegally from Guatemala in the s, and took jobs in factories, or as janitors. They became legal residents when Saul was a boy. Villeda had not planned on being a scientist when he went to college at the University of California in LA. But he enjoyed physiology classes: After Villeda presented his work on conjoined mice to Wyss-Coray at the lab meeting in August , he went on to look at proteins in old and young blood.
He found that the old mice, like old humans, had high levels of a protein called CCL11 in their blood. If you injected CCL11 into young mice, their learning and memory declined. The protein hampered the growth of new neurons. The young mice struggled to remember the location of a hidden platform in a water maze, and took longer to recognise a place where they had received a small but unpleasant electric shock. Villeda published the landmark research in But the study failed to answer a major question: Testing this was by no means easy.
It would be impossible to know how much one had led the other. Wyss-Coray believed that rather than experimenting with conjoined mice, the only option was to take blood from young mice, strip out the blood cells, and inject the plasma into old ones. This, too, was difficult. One mouse yields about microlitres of plasma, the yellowish fluid that contains all the proteins.
That is enough for two injections into another mouse. For an experiment that requires 10 injections into 10 old mice, you need to siphon the blood from 50 young mice. Villeda was reluctant to do the experiment. But he changed his mind when he performed electrical measurements on slices of brain tissue and found that exposure to young blood strengthened the connections between neurons that had weakened in old mice.
He went ahead with the plasma injections. Each mouse had one injection every three days for 24 days. The plasma came from three-month-old mice, the equivalent of human beings in their 20s, and went into month-old mice, the equivalent of a human in their 60s. The results were dramatic. Old mice given young plasma jabs aced the water-maze test, and quickly remembered the cage where they had earlier received an electric shock. They performed like mice half their age. Not everyone was impressed. The journal Nature rejected the study in ; its reviewers felt the work was not a big enough leap forward.
The editors there wanted to know precisely how young blood helped old mice. Villeda, who had just opened his own lab at the University of California in San Francisco, said he would find out. Villeda looked at how young blood altered the way genes are expressed in old mice. He noticed a stark difference among genes that help neural connections strengthen and weaken, a process crucial for learning and memory.
Young plasma jabs ramped the gene activity back up again. From the pattern of genes affected, Villeda traced the mechanism back to a master regulator in the brain, a protein known as CREB, which behaves like a switch that turns on many genes at once, and is instrumental in memory and learning from birth. When they injected the virus into old mice, young plasma had a much reduced effect on their brains.
The animals performed better, but only slightly. It showed that young plasma worked through CREB, though not exclusively. The study was published in Nature Medicine in So did numerous aged billionaires. One, who flies around in a jet with his name emblazoned on the side, invited Wyss-Coray to an Oscars after-party this year. Another correspondent wrote with a more disturbing offer: Wyss-Coray and Villeda were not the only scientists making headway in this area.
Another, Amy Wagers, had begun working at Harvard. She showed that when given young plasma, old mice regained their stamina. On a treadmill, the treated mice ran for an hour on average, compared with only 35 minutes for untreated ones. Wagers picked out one factor, known as GDF11, as a rejuvenating protein in young blood. The studies all point in one direction. Among the hundreds of substances found in blood are proteins that keep tissues youthful, and proteins that make them more aged. Wyss-Coray has a hypothesis: In adulthood, the levels of these proteins plummet.
The tissues that secrete them might produce less because they get old and wear out, or the levels might be suppressed by an active genetic programme.
Can we reverse the ageing process by putting young blood into older people?
Either way, as these pro-youthful proteins vanish from the blood, tissues around the body start to deteriorate. The body responds by releasing pro-inflammatory proteins, which build up in the blood, causing chronic inflammation that damages cells and accelerates ageing. It tells us that the age of an organism, or an organ like the brain, is not written in stone. As a business proposition, the transfusion of young blood raises all kinds of fears.
It raises the spectre of a macabre black market, where teenagers bleed for the highest bidder, and young children go missing from the streets. Then there is the danger of unscrupulous dealers selling fake plasma, or plasma unsafe for human infusion. The fears are not unfounded: Havocscope , an online database, tracks the latest prices of all manner of black market goods and services.
The services of a group of former military snipers? The list includes human organs too, mostly lungs, kidneys and livers. In some countries, there is already a legal market for blood plasma. The fresh plasma is separated from the blood, and the red blood cells returned to the bloodstream, in a sitting that lasts 90 minutes.
The plasma is used in medical procedures, to treat coagulation disorders and immune deficiencies. The business is completely legitimate, but if young plasma is proved to have anti-ageing effects, the risk of backstreet operators setting up will soar. When I asked Wyss-Coray if the prospect worried him, he looked serious.
These are worst-case scenarios. The Stanford trial may find that simply injecting young plasma into old people has little or no effect. In the time when our Lord still walked this earth, he and St. Peter stopped one evening at a smith's and received free quarters. Then it came to pass that a poor beggar, hardly pressed by age and infirmity, came to this house and begged alms of the smith. Peter had compassion on him and said, "Lord and master, if it please thee, cure his torments that he may be able to win his own bread. Peter blew the bellows, and when the coal fire sparkled up large and high our Lord took the little old man, pushed him in the forge in the midst of the red-hot fire, so that he glowed like a rose-bush, and praised God with a loud voice.
After that the Lord went to the quenching tub, put the glowing little man into it so that the water closed over him, and after he had carefully cooled him, gave him his blessing, when behold the little man sprang nimbly out, looking fresh, straight, healthy, and as if he were but twenty.
The smith, who had watched everything closely and attentively, invited them all to supper.
He, however, had an old half-blind crooked, mother-in-law who went to the youth, and with great earnestness asked if the fire had burnt him much. He answered that he had never felt more comfortable, and that he had sat in the red heat as if he had been in cool dew. The youth's words echoed in the ears of the old woman all night long, and early next morning, when the Lord had gone on his way again and had heartily thanked the smith, the latter thought he might make his old mother-in-law young again likewise, as he had watched everything so carefully, and it lay in the province of his trade.
So he called to ask her if she, too, would like to go bounding about like a girl of eighteen.