Ep. 108: Can Metformin Fight Aging? With Dr. Nir Barzilai
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As you get older, your chances of getting sick and developing diseases get higher. But what if aging itself is the condition we should be treating? Scientific studies indicate that the diabetes drug, metformin, may be the anti-aging drug that medicine has long sought. Dr. Nir Barzilai is the founding director of the Institute for Aging Research at the Albert Einstein College of Medicine and the world’s leading expert on metformin. Here, he joins host and Medcan CEO Shaun Francis to discuss the potential of metformin to fight aging, and other potential gerotherapeutics, like rapamycin and SGLT2 inhibitors.
LINKS
Metformin studies conducted by Dr. Nir Barzilai include two from the journal, Cell Metabolism, including Benefits of Metformin in Attenuating the Hallmarks of Aging (2016) and Metformin as a Tool to Target Aging (2016).
Learn more about the upcoming clinical trial Dr. Barzilai is leading, Targeting Aging with Metformin (TAME).
Check out this Dr. Peter Attia podcast featuring Dr. Nir Barzilai discussing metformin, and then here’s an article by Dr. Peter Attia’s team discussing metformin’s interaction with exercise.
Here’s a TED talk by Dr. Nir Barzilai about metformin and aging: Can we grow older without getting sicker?
Dr. Nir Barzilai’s 2020 book is Age Later: Health Span, Life Span and the New Science of Longevity.
Video of presentation by Dr. Nir Barzilai on metformin and aging.
CNBC on metformin use by entrepreneurs: Silicon Valley techies are turning to a cheap diabetes drug to help them live longer
A Critical Review of the Evidence that Metformin is a Putative Anti-Aging Drug that Enhances Healthspan and Extends Lifespan in Frontiers: Endocrinology
Other drugs with potential anti-aging benefits include SGLT2 inhibitors and rapamycin:
SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review
And then on rapamycin: mTOR inhibition improves immune function in the elderly
INSIGHTS
“For me, aging is the mother of all diseases,” says Dr. Barzilai. “Aging happens to all species, and it ends in death, no matter who you are.” Dr. Barzilai regards aging with an evolutionary lens. “When we try to understand diseases, we think of the evolutionary forces that got us to where we are, and what went wrong with them. But aging is all post reproduction, right? We had our kids, [and] if we die the next day … is not part of evolution, because we gave our genes away anyhow. Aging is post-reproduction, so it’s kind of accidental. The major thing that happens in physiology is, when you go into reproduction, you have to have a lot of growth, you have to have everything grow and be strong. But now you go into aging, and you're starting to have a breakdown. And you have to shift the energy… to repair the breakdown. And this is kind of where we are at understanding aging and trying to eventually stop this breakdown.” [4:05, 5:55]
Before we get to the drugs, Dr. Barzilai talks about the effect of lifestyle on aging. The first lifestyle factor, he says, is exercise. “If you can move, if you can exercise — It has unbelievable effects on every organ in your body, your health span and your longevity. This is a major thing.” [9:11]
The second lifestyle factor is diet, Dr. Barzilai says. “Obesity really accelerates aging. Not being obese is really important. But for me it’s only part of the answer.” So it’s not only how much you eat – other lifestyle factors, according to Dr. Barzilai, are how you time your eating, and what type of foods you eat. He talks a little bit about calorie restriction coupled with adjusting the timing of eating to compress feedings into a single eight-hour period of the day, and fasting the other 16 hours. “Fasting is a major way to improve our ability to age better,” says Dr. Barzilai. [9:50, 11:23]
“One drug that is certainly a gerotherapeutic is called metformin,” says Dr. Barzilai. “It's a drug that's used for diabetes. It's a drug that was used 78 years ago to prevent flu, malaria, inflammation, and then it was discovered that it lowers glucose in people as well. And so it was hijacked for diabetes… So it's been out there and we learned many things about it. We learn that in clinical trial, that's controlled trials, okay, where half of the people getting and half are not, it prevents diabetes, it prevents cardiovascular disease, it prevents cognitive decline. And there are association studies, a lot of them, that shows that there's less cancer, all kinds of cancers are decreased. There's less Alzheimer’s. And there's even less mortality. People on metformin not only have half the mortality of other diabetics, but they even have less mortality than non-diabetic patients.” [20:19]
Shaun asks, Are there other drugs or molecules out there that might have a benefit that’s similar to metformin? “From our knowledge, the most important thing that we noticed this year, in the last couple of years—several companies are doing this drug, that is this SGLT-2 inhibitor. It's used for diabetes. And investigators have noticed that people who get this drug, not only does their diabetes improve, but their heart condition and kidney condition is improved. When you give this drug to animals, they live longer and healthier. … And the third drug is called rapamycin. Rapamycin is increasing the healthspan and lifespan of animals, the most of any other drug. That doesn't mean that it's going to be as effective in humans, but it's a promising drug, and there's an effort to have some rapalogs — those are derivatives of rapamycin — in clinical trials to show their effect on a variety of diseases. [25:19]