#478 Mitochondria Scientist: The Only Proven Way to Extend Human Lifespan - Dr Mark Tarnopolsky

Mark Tarnopolsky (0:00)

Every antioxidant combination needs to be studied in a human, because you sometimes don't know if that combination is going to be pro-oxidant, antioxidant, or neutral, where they showed that when people took vitamin E and vitamin C, the adaptive benefits of exercise were completely eliminated. The only thing that's ever going to be proven to extend lifespan, that probably in our lifetime is ever going to be proven in humans, is-

Siim Land (0:24)

Dr. Mark, welcome to the show.

Mark Tarnopolsky (0:26)

Thanks very much, my pleasure.

Siim Land (0:28)

Yeah, I'm excited to have you, because you've talked a lot about the mitochondria, which are very interesting organelles, and they're very relevant in the health and longevity space as well. So yeah, I'm happy to talk with you about all things mitochondria. So essentially, maybe we can start from high school. We know that mitochondria are the powerhouse of the cell, but it's obviously a little bit more complex than that. So maybe you can give us like a more brief overview, an introduction, what are the mitochondria?

Mark Tarnopolsky (1:04)

Yeah, the mitochondria are thought to be an invader, if you will, of our cells. Probably two billion years ago, as we were evolving, we took on the mitochondria, which was thought to be essentially a form of purple photosynthetic bacteria. And what it did really is helped us to detoxify oxygen, but also more importantly, to extract energy.

So throughout 200, sorry, two billion years of evolution, we've remained in close association with the mitochondria. So what they do is they provide ourselves essentially with energy. And because they do that, it's called a symbiotic relationship. So we allow them to stay within our cell in order to conserve our energy and to provide more bang for the buck. As you mentioned, most people feel that it's just energy, it's the powerhouse of your cell, but mitochondria do many more things. And perhaps it's maybe more important to know what they do when they're not working that causes more of an issue. Certainly with aging, with the genetic mitochondrial diseases that I see, even with things like dysglycemia, things like obesity, when mitochondria don't work, it causes problems for the cell. So when mitochondria aren't working, not only do we not get enough ATP or energy, but we also can activate processes like inflammation, oxidative stress, so these free radicals, which can damage protein, DNA and lipids, which can then cause damage to the cell. There are various other processes. There's one called apoptosis or apoptosis, depending on how you want to pronounce it, which is a form of pre-programmed cell death. They're linked to shortening of our telomeres. And many people are aware that telomeres are essentially these replicometers at the end of our chromosome. And as we go through our life and we continually make new copies of DNA, these telomeres shorten. And when they get to a certain level, the cell kind of goes into a senescent state. So they're linked to many cellular processes. The other one, of course, that any older adult with thin muscles is aware of is we have smaller muscles and we need energy to drive what's called protein synthesis. So when they're not working, they have a litany of effects on our cells. So keeping them healthy is an important construct when we think about healthy aging and healthy lifespan.

Siim Land (3:24)

Yeah. I mean, that's very, I guess, somewhat surprising as well as very interesting, the idea that they're like a different life form inside of us, essentially, that help us to produce energy. And without your mitochondria, life as we know it probably not like exists as humans. Or maybe we would have developed some different adaptations. But how big of a role does the mitochondria play in just, let's say, aging and longevity?

Mark Tarnopolsky (3:59)

Yeah. It's a good point. And we know that certainly humans cannot live without mitochondria. We have children who have severe mitochondrial disease and sometimes are dying in infancy, uncalled up to the neonatal ICU. Kids have what's called lethal infantile mitochondrial disease. And even then, they still have some functional mitochondria, but it's not enough to sustain life as we know it. So they're absolutely essential to life. What we see over time is even a small diminishment of mitochondrial function can contribute to muscles being thinner, various theories of aging. One of them is this inflammation, where there's low-grade inflammation, which can be linked partially to mitochondrial dysfunction. So there's a litany of deleterious effects that happen when these aren't functioning properly. But it's a very interesting point that evolutionarily what happened is as a bacteria, probably takes around 1300 genes to make a mitochondria. We still have this little piece of mitochondrial DNA, which is really a throwback to the fact that they were bacteria at one point in time. And 37 or 38 genes, depending on how you look at it, are still encoded for by this little piece of mitochondrial DNA, which we get from our moms. And moms pass this on to all of their children. But that really forms the backbone of the mitochondria. And then the nucleus of our cell makes all of the other components, which then come in and help us to form these elegant structures, which exist in every cell in our body except for our red blood cells. And we see them in much higher abundance in important tissues like heart, brain and muscle, where the high energy demand really dictates that we need lots of mitochondria in order to survive. Whereas other tissues, you know, they're in lower abundance, but still important. We've even published with aging that we have mitochondrial dysfunction in skin. And that can, as we'll talk about later, improve with exercise training.