Tony Wyss-Coray, neurologist: “We can do a blood test and find out what you’re going to die from” | The science

Molecular biologist Tony Wyss-Coray (Aarau, Switzerland, 60 years old) has been immersed in the mysteries of blood for more than ten years. This professor of neurology at Stanford University (USA) is researching the anti-aging potential of certain components of the blood of young people. Blood transfusions have been shown to have a restorative effect, especially on the brain, and this has been confirmed in patients with Alzheimer’s disease, although this study…

Molecular biologist Tony Wyss-Coray (Aarau, Switzerland, 60 years old) has been immersed in the mysteries of blood for more than ten years. This professor of neurology at Stanford University (USA) is researching the anti-aging potential of certain components of the blood of young people. He showed that blood transfusions had a restorative effect, especially on the brain, and confirmed this in patients with Alzheimer’s disease, although this study was suspended due to lack of funds. Visiting Spain for a conference at the National Center for Cancer Research (CNIO), Wyss-Corey talks in this interview about his latest discoveries, such as a blood test that determines the age of each of our organs and calculates the risk of premature death.

Ask. You said that the fountain of eternal youth is inside each of us, but over time it dries up. What do you have in mind?

Reply. With age, the composition of the blood changes dramatically. We can take young blood and give it to an old person and make him younger. This suggests that we have something inside us that keeps us young, but as we age we lose it. If you could constantly give someone young blood, their body wouldn’t age so quickly.

TO. At his conference, he explained that we age in waves. What does it mean?

R. Aging is not linear. There are youth-specific proteins that increase in levels from the time we are born until we reach middle age; and others associated with aging, the level of which begins to increase in the last third of life. We see big changes around the age of 40. Then there is a plateau, then another big change at age 60, and finally a big peak at age 80, when most of us die. This entire process is characterized by the type of proteins circulating in the blood.

TO. Can’t these waves be stopped?

R. No, because we don’t know which switches cause us to change phase. Moreover, we do not know whether these molecules are a reflection of the aging of the body or are responsible for it. We’re talking about thousands of different molecules. For each of them you will have to conduct an experiment, and this is difficult.

TO. But it has been noticed that young blood is rejuvenated.

R. There was a study led by Tom Rando (a researcher at Stanford University) that showed that young blood rejuvenates muscle stem cells. As you age, muscles stop repairing because stem cells stop doing their job. This experiment demonstrated in mice that young blood reactivates muscle stem cells. It also affects other tissues, such as the blood-forming cells that make up the immune system. We’ve seen something similar in the brain. Another interesting observation is that as we age, inflammation throughout the body increases, and young blood appears to calm this process as well.

TO. Because?

R. We do not know. I don’t think it’s stem cells, but rather the active influence of blood proteins. We also know that plasma removal in older adults is beneficial because the body is likely to accumulate toxic factors over time.

TO. You and other groups are testing these effects in patients with Alzheimer’s disease. What has been observed so far?

R. We tried giving patients plasma from young people. The same procedure, apheresis, is done in cases where it is unclear what disease the patient has, for example, autoimmune diseases or chronic fatigue syndrome. And there are advantages.

TO. What were the results for Alzheimer’s disease?

R. Grifols conducted a phase 2-3 study several years ago. This has shown clear benefits for patients. The ones we did with Alkahest, which I co-founded, weren’t as convincing because of the small number of patients; but Grifols patients showed clear improvement in a double-blind and controlled study. But no progress was made.

TO. Because?

R. Because Grifols has no money. They had a lot of problems during the pandemic and then they turned to the European Union and banks for a lot of soft loans. Interest rates have risen and now they only have debt. They were also accused of poor accounting practices. They don’t have money to continue rehearsing. The other major problem is that they couldn’t make money from it. Grifols sells plasma and it is a relatively cheap product. How could they charge five times as much to provide it to people with Alzheimer’s?

TO. Even if it turned into a treatment, you say it might not be possible to implement, why?

R. Because the benefits have been seen not only in people with Alzheimer’s disease, but also with other diseases. Sarcopenia (loss of muscle mass), heart disease. Millions of people could be treated with plasma and it would be beneficial. The problem here is that there won’t be enough plasma to cure everyone. There are rich people who pay for plasma transfusions, and they did so long before all this became known.

TO. Are these treatments reliable?

R. No. It probably has some benefit, but there are only isolated cases of improvements in overall health as well as cognitive function. In fact, this is how Alkahest was founded. The funds were provided by a wealthy family from Hong Kong. The head of the family suffered from Alzheimer’s disease. He received a blood transfusion because he also had cancer. His grandson realized that every time his grandfather had a blood transfusion, his memory returned and he could talk to him again. It was he who provided the funds. (This was Chen Ding Hwa, a Chinese-born billionaire who finally died in 2012. After seeing the extraordinary effects of blood transfusions, his relatives provided funds to create Alkahest. The company was acquired by Grifols in 2020.)

TO. Is there another way to unblock this situation?

R. I hope so, but it’s very difficult. There are tens of thousands of proteins in plasma, and among them there are hundreds of thousands of different variants. We don’t know which ones we need. Here we return to the problem of the fountain of youth. Perhaps the anti-aging proteins found in our blood are in a different conformation than if we synthesized them in the laboratory. For each of them, animal experiments will have to be carried out, but this is a huge and very expensive task; We are talking about 10,000 molecules. There are now many companies dedicated to identifying some of these anti-aging factors.

TO. Can they be turned into a drug?

R. It’s Complicated. In the European Union, the USA, in almost any geographical area, the use of one compound, a specific molecule, is usually permitted. If we need a shake of, say, 10 proteins, how do we do it? Do we test each of these separately in patient trials? How do we know those 10 are better than just five? And what’s worse, there’s nothing stopping a competitor from stealing your idea, because we’re talking about proteins found in plasma. There are many problems that need to be solved.

TO. Are you pessimistic?

R. No. I think that, no matter what, we will see some kind of treatment of this type, perhaps in the next 10 years. Because we can clearly identify the factors that are beneficial for something specific. They may not have the same beneficial effects on a whole-body level, but they are still beneficial. And then, we know very negative factors that we could neutralize. Perhaps this option is the most viable.

TO. Let’s get back to aging. I’m 44 years old, but my brain or heart may already be 55. Does this increase my risk of Alzheimer’s or premature death to a very high level, even more than smoking?

R. Just like that. The risk of death with a very old heart is five times higher than with smoking. But these are rare cases. Most people’s organs are fairly adapted to their age.

TO. How to find out the age of each organ?

R. Some proteins come from certain organs and give us information about their health. The amount of these proteins in your blood may be normal for your age or for people younger or older than you. This way we can estimate the approximate age of your organs. This makes me wonder if disease is nothing more than a reflection of aging. If your heart ages too much, there will come a time when you will be told that you have heart disease. If it is your brain, you will suffer from Alzheimer’s disease. What we don’t know is why people tend to have only one organ that is older than normal.

TO. But does it work the other way around, can a younger organ rejuvenate the rest?

R. If you have a young brain, you will live longer. If you have a young immune system. It is unclear whether this is an anti-aging effect or simply an effective immune system that protects against disease. It is the eternal question of cause and effect. Genetic? How do lifestyle and diet contribute? We do not know.

TO. The organ that poses the greatest risk of death if you are older than average is the brain. Why?

R. Dont clear. Perhaps because this organ regulates many more processes in the body than we think. Of course, it controls the production of hormones, affecting the entire body, but perhaps also other factors that regulate the functioning of other organs.

TO. One of their latest studies was based on 50,000 patients from the UK Biobank. There are already a considerable number of cases. What is needed to be able to apply these discoveries in medicine?

R. We must study people before and after a particular intervention and see how their organs react. This requires longitudinal studies, that is, multiple samples of many patients, to confirm whether the intervention is truly effective.

TO. With data from many more patients and the ability to analyze, perhaps through artificial intelligence, how far can we go?

R. We can probably do a blood test on a middle-aged person, find out what illnesses they have, and calculate when they will die.

TO. It’s pretty scary.

R. Only if you can’t do anything about it. But this has always been the case in medicine. We need to know who is most at risk. For example, high cholesterol and heart attacks. There used to be entire families in which everyone died of heart problems at 50 or 60 years old. It was later discovered that this was due to certain genetic mutations, and studies in this population helped show that controlling cholesterol levels is beneficial for everyone.

TO. What if the analysis says that the brain is very old?

R. It’s even worse because there’s nothing much to do. Although for the first time there are drugs that appear to have a small positive effect against Alzheimer’s disease. Now we conduct clinical trials on patients without knowing the age of their organs, and often the drugs do not show effectiveness. But what if we created such an experiment for patients whose brains are older than normal? We may be seeing that these discarded medications are benefiting them. That’s why I think there will soon be studies that are more focused on people at high risk of developing Alzheimer’s disease.

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