Fifteen Questions: David Sinclair on Age Reversal, Exercise, and Immortal Yeast Cells

David A. Sinclair is a Professor in the Department of Genetics at Harvard Medical School. This interview has been edited for length and clarity.

FM: To start out, you study aging and longevity — why do we age?

DAS: Well, scientists still debate what fundamentally causes aging, and there are at least a dozen so-called hallmarks of aging.

In my lab, we hypothesized that there’s an underlying cause of all of these hallmarks, which is a loss of information. We call it the information theory of aging. The theory is that we lose the two types of information in the cell over time. One is genetic, and the other, which we think is most important, epigenetic — the control systems that tell each cell which genes to switch on and switch off, and so that over time, our cells lose the ability to regulate their genes, and the cells lose their identity. They become dysfunctional, and they get diseases of aging. And the theory also predicts that aging will be reversible, because we have a backup copy of useful information in every cell.

FM: Is there any evolutionary advantage of aging?

DAS: I don’t think so, except in very rare cases. The current thinking is that aging is a lack of natural selection after an age where we become dispensable. And so for humans on the African savannas after age 50, there wasn’t a great deal of use for us. We had already reproduced and produced enough children to replace ourselves, and so our bodies have not evolved to live much longer than that. Conversely, if you’re a whale and you have no predators, it makes sense that they evolved to have children less frequently. But it was useful to continue to survive for up to well over 200 years.

You live as long as you’re useful, and how long you are likely to survive.

FM: Mastering aging in humans may be quite a ways away. But how far are we from, say, an immortal mouse?

DAS: Oh, still, a long way from an immortal mouse. For the last 100 years, we’ve been working on this as a field, and the longest we’ve made a mouse to live is about three times longer.

Immortality seems a long way off currently, even for a mouse. We can’t even make an immortal yeast cell.

FM: If you could choose — how long would you like to live?

DAS: I would put it this way: If I remain healthy, then I can’t imagine there would be a day I would want to die.

I just have so much to do that I still haven’t achieved. Making a medicine that treats diseases of aging. Improving the health of children. Having aging declared a treatable medical condition.

FM: My sense is that anti-aging research has seemed to gain a lot of momentum recently. What do you think has enabled the field to grow so much?

DAS: Three things happened. One is that the field advanced to a point where we were making a lot more progress. Given trials had started, I think it became more realistic that we could not just treat worms and flies and mice, but perhaps people one day.

The second thing that happened was the pandemic forced everybody to understand their mortality, even if they were young. That led to an increase in health and wellness interest and industry.

And then the third is scientists. A few of us in the field wrote books, and those books sold well. My book has sold over a million copies, and I think that that has helped increase the public’s awareness of longevity as something that might be treatable.

FM: I know it takes a significant amount of time and due diligence to translate laboratory findings into something that can be safely used in the clinic, and my sense is that this has driven a lot of medical researchers to be somewhat guarded about what they say and the ways they share their research.

Do you think longevity researchers have been too cautious with what they share or not cautious enough? And how do you communicate promising research to the public in a way that doesn’t overpromise?

DAS: It’s difficult to talk to the legacy media and not have words twisted or hyped, and I’ve experienced that my whole career. But it’s a trade off. I do feel that scientists have a responsibility to talk about the research that the public pays for with their taxes and to start a conversation in the public about the future and also the ethics of what’s going on.

I’ve accepted interviews on occasion with the media and been as honest and transparent as I could about the research. And I know that that frustrates some colleagues who believe that scientists shouldn’t be talking to reporters often when they call. But it is very difficult to stop the exaggeration, because that’s how the media works. And even if my colleagues and I would give the nuance that we don’t know much yet, the headline would often ignore the subtleties of what we were saying and make an outrageous claim — much to the chagrin of colleagues.

FM: Why do you think a lot of this work has been met with controversy?

DAS: One reason is the psychology of it — that it was, until recently, considered selfish to talk about slowing down aging, because the prevailing view was that aging is something you have to accept. It’s natural, and you try to do anything about it — gosh, you must be so selfish to not accept what everyone else is accepting.

But more and more in the public and in the medical profession, we no longer accept that it’s okay to go blind and deaf and to lose our memory at any age.

You know, another controversy is that the field has received a lot of media attention because it’s new, and it could be world changing, and secretly, many people want to live longer — even if they don’t admit it. And so there’s some resentment that the field got and continues to get media attention.

I’d say resentment from colleagues mainly, the public just doesn’t mind.

FM: To talk a little bit more about your research specifically, your research has led to some very promising therapeutic developments, perhaps the most prominent being vision restoration. Could you talk a little bit more about that work?

DAS: The information theory of aging predicts that every cell in our bodies has a backup copy of information to be young again. We think that it’s epigenetic information, and we’re looking for where it’s stored. But we did discover — even without knowing where this backup copy of information is — how to turn it on, how to reinstall the software itself.

First of all, we showed that we could reverse aging, for the first time period, in an animal. Then we also showed that it led to improvements in the nerve function, and in the case of old age and glaucoma, marked improvements in vision.

So now we’re at the point where monkeys have been treated with the three-gene therapy, and their visual function has been improved. And if all goes well, the first blind patient will be treated in August of 2025.

In collaboration with George Church’s lab, we’ve been able to show that the lifespan of mice can be increased as well — which means it’s not just the eye that we can improve in health, it’s seemingly the entire animal. And so we’re also working on ways to rejuvenate the entire body.

Now we’re finding that reversing the age of a mouse’s brain allows it to learn again, and even seems to recover lost memories and improves memory in a model of Alzheimer’s disease — leading us to the hypothesis that diseases of aging, no matter what they are, can be cured, or at least treated, by making the body younger again. And then the body heals itself.

FM: What brought you into this specific field of medical research?

DAS: Well, it wasn’t really a field of much when I started.

My grandmother was a very forward-thinking — and also forward — person, and said, ‘David, one day I will die, your parents will die, your cat is going to be dead, and then you’ll die.’ And I was four years old, and that was a lot to take in at the moment, and I still remember that. My grandmother was a real influence on me. She inspired me to do great in the world. She had escaped from Hungary after World War II and saw the worst of humanity.

She thought that in my generation, we could reach our real potential — rather than fighting with each other, killing each other. So I was really inspired by my grandmother to make use of my life and to have as great an impact as I can. I think what’s still driving me — though she’s passed on now — is the thought that I’m trying to live up to my grandmother’s wishes.

FM: Where do you expect to see the longevity field be in the next 15 years?

DAS: I expect a merger of technologies. We’ll be monitoring our bodies continuously for illnesses that we don’t even know about yet. And then we’ll be prescribed medicines that can treat diseases by reversing aging. And so to that end, my lab is working hard to bring the cost of age reversal down from $100,000 a treatment — which would probably be the gene therapy cost — down to a few $100 for the cost of goods.

FM: In general, do you think the field is more focused on slowing the process of aging, or reversing effects of aging once they’ve already happened?

DAS: In the field of longevity, almost everybody’s focused on slowing aging. It wasn’t too long ago when it was very controversial to talk about reversing aging — and to some extent it still is, among my colleagues — but in my lab, we’ve clearly shown that aging is reversible in many tissues and organs, and even in the whole animal.

FM: Talking about drugs for longevity, drugs like metformin and rapamycin seem to be very popular for longevity and are being used off-label quite extensively. I’ve often heard you respond to questions about these drugs by sharing your own personal regimen, while cautioning that you yourself are not a medical practitioner. And so I’d like to ask you, should doctors encourage patients to be using these drugs off label?

DAS: No! They shouldn’t be encouraging them to do anything that isn’t part of a medical treatment. If a patient is interested in it and educated, then yes, they can have a conversation with the patient. I don’t think that encouraging is the right word. We don't know enough about the long term impact of rapamycin for sure — metformin is a lot less risky.

There are some signs and animal studies and some retrospective studies. I think it looks very promising, and I’ve chosen to use myself as a guinea pig.

But I don’t recommend it. I’m using myself as an experiment. I wouldn’t say that these drugs are for everybody and that lifestyle changes should be done first and foremost.

FM: Were you interested in science growing up, or was it something that you found yourself drawn into later?

DAS: I’ve always been a scientist from the beginning, my parents are scientists. At the dinner table, we talked about glucose levels.

So yeah, I really was destined to become a scientist.

FM: If you were not to work in research or healthcare, what would you do?

DAS: I couldn’t imagine doing anything else. I wanted to do what I do and worked towards it my whole life.

I might draw and paint more often, but in terms of the career I’m doing exactly what I want to be doing. I think I’ll need to be escorted out of my lab to the grave at one point.

FM: I have one last question for you right now. What should college age people be thinking about to stave off aging?

DAS: 20 years ago, we didn’t know if aging was happening early in life. Now we know aging begins at conception, and that every day matters, and there are things you can do in our lifestyle that slow the pace of aging, including at college age.

If I was in college, and I knew what I know now, I would eat less often. So I would have a smaller eating window every day. I would exercise every other day, with weights and a bit of aerobic exercise. I would eat much better than I did in college, a lot fewer pizzas and processed food. A lot more plants and unprocessed food would be in my diet. I also would get better sleep.

I’d work on learning meditation, learning stress relief. And focusing on personal growth, because it’ll pay off — not just in longevity, but you’ll have a happier life as well.

I would drink a lot less alcohol. In fact, these days, I rarely drink alcohol because it’s a neurotoxin. It’s thought to shrink the brain, and we all need our brains to be in good condition.

Remember that how you live your life now is a record — a permanent record — and your rate of aging matters. It depends on how you live each day.

— Associate Magazine Editor Corey Becker can be reached at corey.becker@thecrimson.com.