Aging researcher Coleen Murphy: ‘All the doctors in the longevity field are taking metformin’

In 1974, Sydney Brenner published a paper on the genetics of a worm, Caenorhabditis elegans, which founded a new field of study. That tiny animal, just one millimeter long, became a surprisingly reliable model for understanding the genetic regulation of many processes, including aging. Millions of years of evolution may separate humans from the worm, but it has been proven time and again that many of the mechanisms observed in the worm are also seen in flies and mice, the favorite animal of biomedical research.

American researcher Coleen Murphy became interested in these worms when she learned of the work of Cynthia Kenyon, who discovered how a single genetic mutation, in the daf-2 gene, doubled the lifespan of the C. elegans. First as a postdoctoral student at Kenyon and later as director of the LSI Genomics Institute in Princeton, she has used worms to understand how aging affects learning, memory and reproduction. Last year, she published How We Age: The Science of Longevity, a book which reviews the latest advances in the science of longevity and considers how they can prolong healthy living in humans.

Question. What is the goal of aging research?

Answer. There are people in the field of longevity concerned about extending life, but that is not the reality for most people, who consider slowing down the onset of diseases that come with age: neurodegenerative disorders, cardiovascular diseases and certain types of cancer. It’s about keeping people as healthy as possible, as long as possible.

Q. Is it possible to treat aging as a disease?

A. The FDA does not consider aging a disease; for this reason, progress in the development of anti-aging drugs has been slow. There is a trial by Nir Barzilai and others who are trying to do that type of trial with metformin [a drug used for diabetes]. Metformin is one of those things that might slow down aging and you should be able to do a clinical trial that shows whether or nor metformin slows down at least the biomarkers of aging.

Another way to approach the problem of testing an anti-aging drug is to use age-related diseases as a proxy for aging. That’s smart because you can test that a drug is safe or has an effect on a disease, and it’s faster than testing the effects on longevity. There are several companies that are using this approach, with diseases such as osteoarthritis or macular degeneration.

Q. Billionaires in the tech industry are financing laboratories that seek to slow down aging and even take supplements to prolong their lives. What do you think about this?

A. I’m not a doctor, so I can’t give medical advice, but a doctor in the field told me that everyone in the longevity field is taking metformin. They prescribe it for themselves. That can be done because metformin is quite safe, it’s very well tested, it’s an old drug. In general, I am excited about companies that are seriously doing clinical trials, because I think one person taking a drug and deciding whether it works or not is not scientific. It’s not going to tell us anything informative at the end. It’s also important that companies doing clinical trials tell us whether the drugs work or not.

Q. Is it possible for there to be a treatment that works when you are already very old, or does the fight against aging have to start at a very early age?

A. That’s an important question that, for a long time, I think the longevity field was ignoring. They would do experiments in young mice and say that it extends lifespan, but nobody wants to take a drug when they’re 20 for the rest of their lives. The question is: can we start a drug when we’re 60 or 70 and still see positive effects? My guess is that there will be positive effects, but we need to test things to make sure.

When I was in Cynthia Kenyon’s lab, she and others discovered that you can tweak mitochondrial genes and prolong the life of worms, but you could only do it when they were larvae, basically like treating teenagers. If you did it too late, it wouldn’t have a positive effect. By contrast, when they did the same type of experiment, reducing the activity of the insulin signaling pathway, it was seen that you could achieve effects on longevity much later in life. That’s an example of a pathway where if you had the analogous situation in humans, you could take a drug that would basically change metabolism late in life and would be very positive for aging.

Q. Do you think there is a limit to how long life can be extended?

A. We have managed to increase our life expectancy by changing things, such as childhood diseases and sanitation, that have nothing to do with aging. We are reaching a point where it could be increased by other means. I think there is a limit to unassisted lifespan, and there will be another for people who start taking the drugs we are taking now. I think we are not going to live longer than 200 years, that is not realistic. But for me the question is not so much how long you can make people live for, but how many people are going to live longer in health, also at the end of life. We are going to see more very healthy 85-year-olds who are not going to be in hospital. That is the real goal for most of us.

Q. Can we learn something from centenarians? Many do not eat particularly healthy diets, and some even smoke.

A. They are not a good example, because they have won the genetic lottery. But we can learn about the genes related to their longevity and they are the same genes that we see when we study in C. elegans. The insulin signaling pathway, the FOXO gene, is modulated in a particular way in centenarians that we also see in worms. The idea would be to modulate these genes in the same way that we see in centenarians. Following the diet of one of them as an example is not so useful.

Q. Can you give some basic advice to live longer based on the research in the book?

A. There are things that we know slow down aging or the appearance of problems that come with age, but they are things that people know and kind of boring. Everybody wants me to tell them a magic trick that’s really easy, like just eat 12 blueberries a day, but I don’t have on. The data tells us that things like not overeating or the Mediterranean diet are positive. I think exercise is the one that is underappreciated because everybody likes to talk about diet all the time. But the truth is that exercise has so many beneficial effects that we’re just now starting to understand, and I think it is going to be what helps people the most. I also don’t know the one exercise that people can do and live forever, it’s not the work I do. When we study aging in the laboratory, we’re trying to understand what happens in the cells when you do those things to better understand the process.

Q. In the book, you give an interesting fact about the most extreme fasting diets: for every 21 men who go on a fasting diet, there are only four women. What are these differences due to?

A. It’s something I’ve been thinking a lot about lately, and about GLP1 agonists, like Wegovy, Ozempic and Mounjaro. We cannot ignore brain chemistry. Oprah Winfrey has said that she always thought it was her fault that she was overweight, and it is interesting that patients have reported when they take these drugs that it changes how they think about food. They’re not thinking about food all the time. I think for many women, it is much harder to diet and change their eating habits. And I think that it could be very easily hormonal, driven by evolutionary needs, because our metabolism wasn’t made to starve ourselves. I think there’s something to this idea that maybe it is easier for some people to eat less, and I think that we’re just finally understanding that it’s not just a moral choice. That is why the new obesity drugs are so interesting, because they’re not just changing people’s metabolism, they’re changing their impulses for food.

Q. Could these drugs, which also seem to prevent cardiovascular problems, be the first anti-aging drugs?

A. I think that people who may have problems with obesity or their metabolism will be able to live longer thanks to these drugs, but are statins [which are taken to control cholesterol levels] a drug for longevity because they prevent premature deaths? It seems that it has to be magical in order for it to be a longevity drug, and when we explain how things work, the response is ‘oh well, that’s not really a longevity drug.’

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