Toren Finkel, gerontologist: ‘We may have hit a biological wall in the fight to prolong life, but walls come down’

This morning, Toren Finkel had a coffee with milk for breakfast, and that ruined everything. The American biologist — who was born in 1957 — said to himself: “What the hell.” He then proceeded to eat croissants, tortilla skewers and puff pastries.

Intermittent fasting is a very good routine. Finkel has been practicing it for more than four years. However, since he arrived in Spain to attend the Longevity World Forum in Alicante, he’s allowed himself to make some exceptions.

The professor of Medicine and director of the Aging Institute at the University of Pittsburgh has come to lecture about a future in which we can avoid old age with pills, as if it were a disease. But until that time comes, he explains, intermittent fasting is the best tool we have at hand. He’s betting on metformin — or the elimination of senescent cells — in the medium-term. And he believes that revolutionary anti-obesity drugs can also be of help.

Dr. Finkel sat down with EL PAÍS to discuss all of this in Alicante, after having a snack during a coffee break.

Question. Why did you decide to study aging?

Answer. Because it’s a biological process that — if we’re lucky — we’ll all go through. And, at the same time, it’s the least understood biological process. We have a fairly clear idea of how cancer begins and how heart disease occurs, but for many years, we had no real idea about how and why we age.

Q. When did this start to change?

A. About 20 years ago, people started studying aging by using very simple models, such as worms. And it was shown that, by changing a single gene, the worm could live longer. This discovery changed the idea that people had about aging. Before this, it was thought that nothing could be done about it, that it was a random and inevitable process. Metal rusts, while living organisms age. But these experiments in very simple animals showed that, by modifying a gene, you could live 15% longer. So, aging obeys certain rules. And, if it’s regulated, that means you can do something about it — it’s not inevitable. So, this question arose: how is it regulated? How does it work? I think it’s the biggest question in biology.

Q. We’re genetically programmed to age and die… is there a way to hack that program?

A. It’s not clear. Our genes were created to make us grow when we’re young and to reproduce and to pass that on. Once we get older, from an evolutionary point of view, we’ve done our job. Some experts believe that the genes that made you grow and reproduce are the ones that make you age as well, but it doesn’t have to be that way. There’s no genetic pressure, because the next generation is the one that matters. So, we wonder if we can take genetic control of aging. And I don’t think anyone knows for sure [whether we can or not].

Q. First, it was religion, then cosmetics and now medicine. We’ve been promising eternal youth all our lives. And the promise continues to be compelling. Why is that?

A. That’s a very complicated question and I don’t think there’s a common answer for everyone. There are some good things about getting older: maybe you’re a little wiser, a little more patient and you see life with a certain perspective. But there are some things that aren’t so good, like your knees hurting, or your back hurting. And people would like to retain their wisdom and lose their discomfort. So, it’s a very attractive idea to think that there’s something that can be done about it. People don’t want to feel powerless in this process; they’d like to take control. That’s why, at certain ages, things like your diet start to become more important. People like the feeling of controlling their destiny, instead of just receiving it helplessly.

Q. And you, on a personal level, do you do anything to fight aging?

A. I don’t take any drugs, but I only eat at night. In the morning, I have a black coffee for breakfast and then I try not to eat until dinner. In the United States, we have dinner at 6 p.m. I don’t know if I could do this routine in Spain, [where they eat dinner much later]. In any case, I try to have a window of between 14 and 18 hours without consuming calories. I’ve been doing it for about four or five years and it works very well for me. Although I’m skipping it here.

Q. Why is it believed that this type of diet can help us to prolong our lifespan?

A. Because of the concept of autophagy. This process [which starts after going many hours without eating] was first described in yeast and the person who discovered it [Japanese biologist Yoshinori Ohsumi] won the Nobel Prize. It’s a very complex process, but the most remarkable thing is that it recognizes damaged proteins and components in your cell and wraps them up in a kind of garbage bag — which is called an autophagosome — and then delivers it to an organelle called a lysosome, which is like a garbage disposal. And every cell has this process where it can clean itself up. It’s like an automated cleaning system inside every cell and tissue in your body. And this is a way of removing accumulated damage.

The idea is that, as we age, we’re not necessarily producing more garbage, we’re just not getting rid of it as efficiently. So, if you don’t throw out your trash, it will build up in your house. It’s thought that this can contribute to developing diseases like Alzheimer’s. So, if we do intermittent fasting — if we encourage autophagy — in theory, we could keep cellular trash at youthful levels and delay the point at which we start to get these diseases.

Q. Studies in mice say that this starts to happen if they reduce their caloric intake by 40%. Is it realistic to think that a person can do that for their entire life?

A. I understand that it’s not easy. There are people who voluntarily eat only the minimum amount of food necessary to survive — which is different for each person — but yes, it’s very difficult. Most people cannot do it. That’s why, in recent years, scientists have begun to wonder if it’s possible to get a drug that stimulates the same process without having to stop eating. It would be like we say in the United States: eating your cake and having it, too. And it’s virtually possible, but at the moment, there’s no way to do it.

Q. And what role could drugs like Ozempic play in all this?

A. It’ll be interesting to see what their effect is on life expectancy and aging. To see if there’s any difference between people who have to make an effort not to eat — because they’re hungry — and those who don’t eat because they feel full, due to these satiating drugs. There may be differences in your body’s response. The effect of not eating may be different if you’re hungry or not hungry, which is interesting because it’s not the same, even though the caloric reduction is the same. Your body physiologically responds differently when it feels full or when it’s hungry. With these drugs, you can achieve caloric restriction, but it still has no effect on longevity. But I think that will come to light with long-term observation of people who are taking these drugs.

Q. You’ve studied anti-cancer drugs that have been reformulated to treat senescent cells, such as PARP1 inhibitors. What can you say about these drugs?

A. People are very excited about this concept of eliminating senescent cells [damaged and aged cells that stop dividing, but don’t die. Many diseases — such as type 2 diabetes, cataracts, arthritis, or cancer — have been linked to the accumulation of senescent cells]. Human clinical trials are underway to try to eliminate these cells with drugs. And my personal feeling is that these aren’t going to be the best drugs. In this field, we’re at the same point that we were with chemotherapy in the 1950s: to kill cancer cells, you killed a lot of other cells, and the side effects were much stronger than today. We need to take that lesson and apply it to aging. Instead of killing senescent cells, we should go back and understand what their unique vulnerabilities are. And then, based on that understanding, design more targeted therapies.

Q. So, what’s on the market right now? If I go to the pharmacy and ask for something to combat the effects of aging, what would they give me?

A. There’s nothing approved specifically for aging. People are taking drugs that have been approved for other ailments, like metformin. It’s a diabetes drug that’s taken by millions of people around the world. Epidemiologically, it’s been observed that diabetics who take metformin live longer. They seem to develop fewer cancers and improve markers that really have nothing to do with diabetes. So, people started to think that this might work in a more general way. And there’s some evidence to be found in animals that are given metformin. It can, for example, extend the lifespan of non-diabetic mice.

There are lots of different theories about how it works. But it seems to regulate some sort of central metabolism of the person taking it, rewiring their metabolism in a way that perhaps mimics fasting. At the moment, however, it’s not approved for use beyond diabetes.

Q. Why is it so hard to find a drug that will help counteract the harmful effects of aging?

A. This is a relatively young field. People have been studying aging for a long time, but they’ve basically been looking at what goes wrong — not why it goes wrong. Also, there’s no single path that leads to old age: we don’t age uniformly. There are people whose brains are perfectly fine at 90, but whose hearts are not. And there are other people who have exactly the opposite situation. Life expectancy is a certain number, but our cells and tissues probably age due to different pathways and mechanisms and at different rates depending on the person. So, it’s a complex problem. It’s so complex that there won’t be a single pill that will cure it, or a single drug that will cure everything and everyone.

Q. In recent years, life expectancy has increased, but quality of life has not. Age-related diseases continue to appear at the same ages they used to appear in the past. Have we reached a biological limit, or is there something we’re doing wrong?

A. Age is the biggest risk factor for almost every disease we get. But it’s not the same as the disease itself. One hundred years ago, life expectancy was much lower. It could be around 40 years on average. We’ve been increasing it, but around the age of 70 and 80, we’ve hit a biological wall. And, recently, a major study came out claiming that Western countries have seen the rise in life expectancy slow down. All the increases that have occurred in the last few decades are starting to slow down.

Now, we may have hit a biological wall in the fight to prolong life, but walls come down. In the 1950s, it was unthinkable that someone could run a mile in less than four minutes. But training, nutrition and equipment improved and, finally, someone beat that record. And they beat it again. And it has been reduced more and more, little by little — not suddenly or drastically. I think aging is very much the same thing. I don’t think that people’s life expectancy will change much in the next 10 or 20 years. But thanks to medicine, nutrition, and healthcare, we’ll be able to continue improving.

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