Nir Barzilai, gerontologist: ‘Just because you look young doesn’t mean you’re healthy’

The doctor asked the elderly woman about her lifestyle. She answered by taking a long drag on her cigarette. “Many doctors have recommended that I quit,” she said through curls of smoke. “But all of them have died.”

The patient was Helen Reichert, and she was 100 years old at the time. Throughout her life, Reichert shared with anyone willing to listen her own peculiar secret for reaching such an age: hamburgers, chocolate, beer, cigarettes, and enjoying New York nightlife. She died at 109.

The doctor asking the question was Nir Barzilai, president of the Academy of Geroscience. Barzilai told the story in Madrid last February, during his talk at the Longevity World Forum, which held its fourth edition in the Spanish capital.

It wasn’t just an anecdote fit for a TED talk; it was a way of illustrating what he does. The Israeli gerontologist has been studying healthy centenarians for years and has observed that many follow a pattern similar to Reichert’s. They do not always lead a monastic, carefully balanced life. There is a great deal of biological lottery involved in longevity. But Barzilai wants to hack that lottery — to understand which numbers are the winning ones and pass them on to the rest of humanity. That is why he has sequenced the genomes of several centenarians.

Barzilai is not a centenarian — he is approaching 70 — but he shows enviable energy, especially considering that he is a bit jet-lagged. He arrived the day before from New York, where he serves as director of the Institute for Aging Research at Albert Einstein College of Medicine.

“It’s because I take pretty good care of myself,” he admits before sitting down to answer questions from EL PAÍS.

Question. Life expectancy has been stagnating or even declining for years. Have we hit a biological wall?

Answer. Statistically, our maximum lifespan as a human species is 115 years. We currently die at 80, so we have a 35-year window. That is a lot, especially if they are healthy years. The question is: can we break this roof? I think so, but I give it 50 years, maybe it will happen in more accelerated rates, but not today.

Q. There are people who reach that age in excellent health. What have you discovered about centenarians, and how can these discoveries be applied to the rest of the population?

A. The reason we analyze the genomes of centenarians is because we believe their advantages are encrypted there. Until recently, we said that longevity was 20% genetic and 80% environmental, but we now know that was incorrect. It’s really a collaboration between both factors, and the number isn’t so important. But in the case of centenarians, things change. It’s more as if they have 80 or 90% genetics, and the environment has very little to do with most of them. That’s why it’s important to study their genes, to see which genetic variations slow down the cellular aging process. We’ve already discovered two genes with a variant that affected their function. We then designed a drug that mimics their effects; these have already become medications.

[The genes with mutations identified by Barzilai’s team were CETP and APOC3. In the former, many centenarians had a variant that increased good cholesterol and reduced the risk of cognitive decline. CETP inhibitors were developed, but they have not been commercially available. Another variant found in 25% of centenarians is in the APOC3 gene, which reduces triglycerides and inflammation. There are medications that mimic its effect, but they are prescription-only and recommended only for patients with extremely high triglycerides who do not respond to conventional treatments.]

Q. In your talk, you mentioned a study that showed the positive effects of the Mediterranean diet could not be replicated in non-Mediterranean populations. That the same diet had three times less protective effect outside of Spain. Why is it so difficult to replicate and export the so-called Blue Zones?

A. Blue Zones have an effect if you’re born there. All aging begins at conception, so it’s difficult to say, “Okay, let’s replicate this healthy lifestyle at 70 and see what effect it has.” Perhaps nothing will be seen because it was something that happened during puberty, or perhaps adherence is lower because it’s not culturally ingrained.

This study caused quite a stir. In all the places where the Mediterranean diet was replicated, the benefits were always less pronounced than in Spain, so it’s possible it’s a combination of the Mediterranean diet and something about Spanish culture. Maybe it only works if you eat dinner at 10 p.m. [laughs]. Maybe the weather is better, life is more sociable... I think it’s another interaction with the environment that’s very difficult to replicate. Especially since your only intervention is olive oil (and by the way, the olive oil in these studies wasn’t the same as what’s consumed here), you might be missing something.

Q. In any case, if life expectancy in Spain is higher than in the United States, I don’t think it can be explained by a collection of individual choices alone, can it? To what extent is living a healthy life a personal choice, and to what extent is it shaped by public policies or by the broader social context?

A. In every part of the world, in every city, including Madrid, poor people live 10 to 20 years less than the rich. [In Madrid, one study put the difference at four years.] There are places where poor people don’t have access to fruits and vegetables. They can’t buy fish. They can’t afford a gym membership, or there isn’t even one in their neighborhood. You can tell them they have to do all these things — everyone knows how to live a healthy life — but to do it, you need money. I would love for everyone we recommend exercise and diet to actually do it, but I know, I see it in my clinic in the Bronx, that when I tell people, maybe only 3% follow through. It’s easy to say, but not so easy to do.

Q. You are very critical of multivitamin supplements…

A. The main benefit of vitamin supplements is that they’re good for the economy. There’s no data to support their use; they’re based on pure hope. And I’m particularly concerned that when taking multiple supplements, assuming they all have some biological basis, some might interact with each other, maybe even antagonize one another. We simply don’t have enough data, and that’s a problem. There’s a study that followed 300,000 people for 20 years, and those who took many supplements had higher mortality. It was only 4% higher, not significant, but you have to keep in mind that we’re talking about people who take good enough care of themselves to spend money on supplements, people who exercise and diet. So it doesn’t seem like they work.

Q. The aging industry was estimated to be worth $610 billion globally in 2025. There’s a lot of money invested in the sector…

A. I’m one of the executives at the Longevity Biotech Association. It’s a global association that brings together all the companies that have a drug that targets the biology of aging from different perspectives. We’re trying to give them knowledge. And I see there’s a lot of interest in the field now. Biotech has had some tough years, but I think a lot of people know that this is the next frontier. Pharmaceutical companies understand that it’s more lucrative to design a drug that you take for life, that will be long-lasting, rather than antibiotics that you take for eight days. In the case of diabetes, you take medicine for years, but targeting the entire population is much more profitable. So there are no longer any difficulties in obtaining funding.

Q. This economic interest has also led to the flourishing of businesses that have little to do with science and much to do with fiction. What are your thoughts on immortalism and transhumanism?

A. Scientists are not immortalists. Immortality is a belief. A faith that arises, probably, from the fear of death. But I don’t think it’s relevant to talk about it in our time. Perhaps someday it will be appropriate, but we’re not there yet. There are immortalists who follow us. They come to conferences. In fact, there are some immortalists here... And when they see the advances, see how we are talking, they understand the timeline and realize that they are mortal.

That’s why they start talking about cryopreservation. It’s not just a scientific plan, it’s a business plan. Let’s say you want to be immortal. You go to one of these companies and they tell you: “Take out a $2-million-dollar life insurance policy and name us as beneficiaries.” The idea is that they cryogenically freeze you with that money. From an economic point of view, it’s perfect, but from a scientific point of view, it has some shortcomings. We can freeze cells from some small animals and then thaw them. They come back to life. With mammals, for the moment, it can’t be done. I’m not saying it can’t be done in the future; I don’t think it will be easy, but they might find a long-term solution. And then what? When they thaw you out, you need two things: a cure for whatever killed you — cancer, heart attack, whatever. And also a cure for aging.

Q. In these cases, the model isn’t the little old Sicilian woman who lives to be 110, but Demi Moore in The Substance. This is not about healthy ageing, but about eternal youth. There is a very important aesthetic dimension to it, not just a medical one.

A. Some of the available medications that have global effects on aging also affect the skin. Many drugs that target the characteristics of aging, such as senolytics and others, are now being developed for the skin [they are still in the experimental phase]. But I agree, I think it’s much more important to focus on the whole body. Just because you look young doesn’t mean you’re healthy. Your body is going to age regardless, despite creams or Botox.

Q. You have training as a diabetologist, how do you explain that metformin and GLP-1 analogues — two drugs originally intended for diabetics — appear to affect aging?

A. Obesity drives aging and disease, so that part is obvious. But we believe that obesity is only about a third of what GLP-1 analogs are doing. They prevent diseases that aren’t related to diabetes or obesity. There was a paper last month where mice were given a fairly low dose of GLP-1 and the same amount of food, so their body weight was similar. But those with GLP-1 showed they lived longer [between 7% and 10%]. Now they’re doing a study to see if they can prevent Alzheimer’s... I think in the future many non-obese people will be using these drugs, perhaps at lower doses. The doses we’re giving now are very high and might make sense if you have diabetes and want to get rid of it in a few months, but for the rest of the population, a lower dose could be sufficient.

Q. And what about metformin?

A. The French lilac extract, from which metformin is derived, was already being used in the 1920s to prevent arthritis; its original use was the same as we are beginning to see now. When it was approved as an antidiabetic drug, they saw that people taking metformin, and not other diabetes medications, had fewer heart diseases and fewer cancers. It also prevented cognitive decline, even mortality. It’s funny, because when I was a fellow at Yale, in 1987 and 1988, I published the first article on the mechanism of action of metformin in diabetes. When I now argue that it can be effective against aging and people tell me no, that it’s only good for diabetes, I ask them to send me a paper that proves it. And they usually send me the one I wrote. And that’s fine, it’s a good article, but one has the right to change their mind, right?

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