Scientists on how to age well: ‘Sleep is democratic, universal, cheap, and free, and yet no one sleeps enough’

The only way to live a long life is by growing old. However, aging is sometimes seen as something undesirable — even as a disease that needs to be cured. The problem is that no one yet knows how to do that; there isn’t even a way to stop the inexorable effects of the passage of time on our bodies.

Despite this, our understanding of aging at the cellular level has advanced significantly in recent years. One of the main figures behind this progress is biologist and physician Ana María Cuervo, 58. Cuervo co-directs the Einstein Institute for Aging Research in New York, which, among other initiatives, is promoting a much-anticipated clinical trial with centenarians to try to uncover the keys to why some people age worse than others. This could one day give all humans the ability to live longer without suffering from age-related diseases — even without following particularly healthy lifestyles, as some centenarians manage to do thanks to privileged genetics.

Cuervo visited Madrid on Tuesday to receive the Conchita Rábago de Jiménez Díaz Memorial Lecture Award, a distinction previously granted to other major figures in research, such as Katalin Karikó, the creator of the COVID-19 vaccines, and paleoanthropologist Juan Luis Arsuaga, who nominated Cuervo. A day earlier, both scientists sat down together to reflect on what aging really is — and whether it’s inevitable. Arsuaga offers the first thought: “We’ve gone from living as long as a chimpanzee — around 45 years — to about 85, in just two million years. We’re not doing badly.”

Question: Does that progress have a limit?

Ana María Cuervo. Before, people died at 50 and suffered for a year. Now, what we’ve achieved is to extend the period of your life in which you are no longer fully functional, you’ve lost your independence, you can no longer drive because you no longer see well, and on top of that, you’re more susceptible to age-related diseases. The challenge now is to ensure that the extra years we gain are lived in the best possible condition — and for that, we need to change the way we age.

Q. Is aging inevitable after a certain age?

A.M.C. There’s a programmed factor, which is genetics. Those who come from centenarian families can go to McDonald’s every day and smoke as much as they want because they have good genes. We asked one of our centenarians if doctors hadn’t told her to quit smoking, and she replied, “Three doctors have already told me, but all three are dead.” What we want to learn from them is what genes or cellular pathways are involved so that the rest of us — who don’t come from centenarian families — can reach their level and functionality. Aside from this, there’s also an environmental component. One topic we’re very interested in is nutrition, and how that exposure is contributing to decline. We begin aging from birth. Everything you’ve done and everything you’ve been exposed to is going to influence how you age.

Juan Luis Arsuaga. Since our entire development is programmed from birth — infancy, puberty, even the end of a woman’s fertile life with menopause — why not think that old age is also programmed? It has even been thought that death is programmed, and it was argued that this would serve the species, by allowing for renewal. But the bad news is that the vast majority of biologists believe that aging is not programmed. That’s why we can’t hack it.

Q. Are there any interventions or treatments that actually extend people’s lives?

A.M.C. For now, there are no drugs specifically approved to prolong longevity in humans. A major limitation has been the lack of regulation for conducting clinical trials targeting aging. The first study of this type in the United States, called TAME, will test metformin, a diabetes drug. Retrospective studies in Nordic countries suggest that diabetics treated with metformin live longer than the general population, but it remains to be seen whether this effect is replicated in other groups or if it may be harmful to some. In Singapore, studies are about to begin on acarbose. Rapamycin — an immunosuppressant — is also being investigated for its possible benefit in reducing chronic inflammation associated with aging. Results are still pending.

Q. Ana María, you advocate for geromedicine. What does it consist of?

A.M.C. We seek to apply advances in the biology of aging to personalized clinical medicine. The idea is that, say at age 50, people could undergo periodic check-ups to detect which aging mechanisms — such as mitochondrial function or cellular cleaning through autophagy — are impaired in each individual. Based on the results, specific treatments would be applied to improve those areas. What’s interesting is that it’s not necessary to fix all damaged processes: the pillars of aging are interconnected, and improving one can have positive effects on the others. It’s a preventive approach tailored to each person. In the lab, we have genetically modified mice whose autophagy does not deteriorate, and they’re perfect — not a single gray hair, no health problems, despite being very old.

Q. Can that be replicated in humans?

A.M.C. Not directly, because it’s genetic modification. But now, thanks to the repurposing of already approved drugs and artificial intelligence, there are hardly any limits to finding molecules that slow these processes.

Q. Do humans today age better than those of previous generations?

J.L.A. No. Life expectancy at birth is declining in the United States and Germany. And it’s basically due to obesity and diet. Life expectancy improved significantly in the last century, especially due to the decline in infant mortality. Now, there’s virtually no infant mortality. Almost everyone born today reach adulthood. However, as much as medicine has improved, it’s not advancing enough to compensate for increasingly poor lifestyle habits.

A.M.C. A lot depends on where you live. In the United States, if you’re from the East or West Coast, you’ll live much longer than in some areas of the interior. If you don’t have money, you can go to McDonald’s and get the whole family a meal for a dollar. The biggest predictor is your zip code, which is linked to your educational level.

J.L.A. The only way to be thin is to starve yourself, to control your diet. Exercise is great, but not for losing a lot of weight. Historically, those who went hungry were the poor. Today, cheap food means you don’t go hungry, no matter how poor you are. Nowadays, it’s the rich who go hungry, because they take care of themselves.

Q. So it’s no longer just about how many calories you consume per day?

A.M.C. Autophagy doesn’t depend on the number of calories, but rather on the spacing between meals and the type of diet. A balanced diet like the Mediterranean one is key — more than counting calories. Factors like sex and genetics play a role. What matters is creating periods in which insulin levels drop, which promotes cellular cleansing. An 8/16 regimen (eating over an eight-hour period, fasting for 16) can be useful, but it must be tailored to each person. The time you eat also plays a role. Mice, which are nocturnal animals, show no benefits if they’re fed during their rest period. Something similar happens in humans: people who concentrate their only meal of the day at unsuitable times, like 2 a.m., have worse outcomes than those who distribute their diet more evenly throughout the day. For example, with lunch and dinner or breakfast and lunch. The circadian rhythm plays a role in how the body responds to eating and fasting.

Q. The brain is the organ that most defines us as a species. Dementia is an age-related disease, but the rate of mental illnesses like depression skyrockets after age 85. Furthermore, loneliness is increasing. Could all of this also be treated with drugs?

A.M. C. Exercise, diet, sleep, which is democratic, universal, cheap, and free, and yet no one sleeps enough in this country or anywhere else. Then there are two other components that until now haven’t been given much importance, which are precisely social relationships, social interactions, and their beneficial or harmful effect, depending on the nature of those relationships. You either use your brain or lose it. Just by listening to me, you’re making new brain connections.

There’s also a negative aspect, like stress and abuse. We see it in the lab. You put a bully mouse in the cage and in the other four, cellular cleaning decreases just from the stress. The last factor that’s been added recently is attitude. There seems to be a very good correlation because you have more endorphins. There are many biological benefits to seeing the glass half full. There’s a genetic component here, but also an environmental one. I come from a very positive family. My father, no matter what happened, always said, “I’m the tallest and the most handsome.” The key is that there’s constant stress that we don’t manage well. If you can at least find a way to manage it in a healthy way, that’s great.

Q: How long do we have to wait before we can get a blood or genetic test and be told what to take to treat aging?

A.M.C. Biomarkers of aging are already being researched, and their clinical application could arrive soon. Circulating factors are being sought to assess functions such as autophagy, mitochondrial health, and telomere status with a simple blood test, similar to current routine tests. The idea is to create a “biological signature” or barcode that reflects the aging status of each person. However, it will still take time before specific personalized interventions can be prescribed — except in cases where clinically approved treatments already exist. That’s why I’m so excited about clinical trials, because the amount of information that will come back to the labs is tremendous.

J.L.A. The big problem with human aging is that we’re a slow-growing species; it’s much harder to experiment, and not just for ethical reasons. If you die at a certain age, it’s impossible to know: if I had done things differently, could I have lived longer? There’s only one solution, and that’s to be able to reverse aging. That will be the day when there’s no doubt that we control it. If it’s an epigenetic process, not a genetic one, then we can reverse it. Epigenetics is like software; we can change it. But genetics is hardware, and if it’s broken, there’s nothing you can do.

A.M.C. But that’s already been done. When you take an adult cell from an older person and reprogram it — what we call an iPSC — the epigenetic markers disappear. And you have a stem cell again. But you haven’t reversed aging, just the epigenetic markers.

Q. What do you think of initiatives like Altos Labs, funded by billionaires who want to find a cure for aging as soon as possible?

A.M.C. Billionaire investment in aging research, like at Altos Labs, isn’t a bad thing if it’s managed carefully. Although their interest is sometimes purely selfish — wanting to stay young forever — their contributions can benefit society as a whole by driving scientific advances. I don’t feel guilty about receiving money from these people because we know we can do something about aging. It’s better for them to spend it on this than on other things.

Q. Science is going through a very difficult time under Donald Trump. Is it affecting you?

A.M.C. It’s best not to comment directly on the situation, but I do want to convey a positive message. Scientists are trained to be resilient, and research will continue, one way or another. What worries me most is ensuring we don’t lose a generation of scientists. In Spain, cutting-edge science is done with very few resources, thanks to ingenuity and creativity. And that shows that resilience is possible. But we also need young people to see the enthusiasm, not just the complaints. The best is yet to be discovered, and science remains the best possible career.

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