Is this the Key to Health on a Cellular Level?
Anecdotally, we’d heard that people were reportedly “feeling better” after adding a supplement called MitoQ to their regimen, which is designed to support the health of mitochondria. If it’s been a while since you took Bio 101, mitochondria are essentially the part of your cells that produce energy. Curious to learn more, we interviewed one of the co-inventors of MitoQ and a leading mitochondria researcher, Mike Murphy, Ph.D. Currently, Murphy is a Programme Leader of the Mitochondria Biology Unit at the University of Cambridge (which is not affiliated with MitoQ).
What’s interesting about MitoQ is that it’s the focus of ongoing studies with a number of different research groups, examining MitoQ in animal and human models, and looking at the potential far-reaching impact of mitochondria on overall well-being, especially as we age. That work, and the discovery that led to MitoQ, dates back to the 1990’s, when Murphy was collaborating with a colleague at the University of Otago in New Zealand, looking for ways to design molecules so that they could accumulate inside mitochondria and potentially support their function in the body. Their discovery (which we’ll let Murphy tell you about), was first developed as a potential pharmaceutical by Antipodean Pharmaceuticals, and later spun off to be harnessed into the MitoQ supplement by MitoQ Ltd.
Here, Murphy takes us through what he’s learned about mitochondria, why it matters now, and how it could shape healthspan (i.e. how long you’re healthy for) in the future.
*Note: As self-reported by Murphy, he currently acts as a scientific advisor to MitoQ Ltd. He does not work directly with the supplements or skincare that the company now sells, but he owns a share of the company, so he does have a financial interest.
A Q&A with Mike Murphy, Ph.D.
Why do mitochondria have their own DNA?
If you looked at a cell, you’d see a big blob in the nucleus, where nearly all of our DNA is. Around the sides, there are a thousand or so little mitochondria scattered around the cell; they look a bit like bacteria.
One to two billion years ago, mitochondria were foreign bacteria that slowly became integrated into animal cells as the cells ate the bacteria. So mitochondria have residual DNA from their bacteria origin. The number of genes in mitochondrial DNA is very small—only 37, whereas in the nucleus of the cell, there are closer to 20,000. But while the number of genes is very small, they are critical to the way mitochondria operate and make ATP. The mitochondria wouldn’t work—and we wouldn’t survive—without this residual DNA.
What happens when mitochondria break down?
Mitochondria get damaged and are recycled by cells constantly; there are many natural repair methods in the body. If the mitochondrial DNA is damaged or if the mitochondria isn’t working properly for whatever reason, it goes through a recycling process inside the cell called autophagy: The mitochondria is eaten up and some pieces of it are reused.
How often this happens is an active area of research. People are also studying whether this process changes with age and whether it’s a factor in some diseases. One hypothesis is that neurodegenerative diseases like Parkinson’s may occur when our cells are not very good at clearing the mitochondrial damage that accumulates.
Is there a theory behind the possible connection between mitochondrial damage and aging?
A few years ago, popular theory was that mitochondrial damage was one of the main causes of aging—that this damage accumulated, that it meant the mitochondria weren’t working properly, that the cell then died, and eventually the body died. Now, it seems to be much more complicated: For some reason, the ability to remove damaged mitochondria and replace them with good mitochondria declines as we get older, but we don’t yet know if that’s a cause or a consequence of aging.
Are there lifestyle factors that might contribute to mitochondrial damage?
The key environmental effects we’re always looking at in terms of mitochondria are diet and exercise.
One of the best ways to improve mitochondrial health is through dietary changes; obesity is one of the most damaging conditions for mitochondria. We essentially pass what we eat to mitochondria, so they can make ATP. Having too many nutrients—too much fat, too many carbohydrates or protein coming in—causes extensive damage to the cell and its mitochondria. (We can’t say at this stage if any particular nutrients or foods are more or less damaging to mitochondria.)
You might be familiar with the idea of dietary restriction to extend lifespan. Note that this is very distinct from malnutrition—total calories consumed are reduced but it’s crucial to take in the correct amount of nutrients and vitamins. The field of dietary restriction is well-established in animal models—in studies with worms, flies, mice, monkeys, and so on, it’s been shown that animals live longer and healthier under dietary restriction. While the mechanisms by which dietary restriction works to extend lifespan are not entirely clear, it’s highly likely that mitochondrial function plays a role.
The problem with dietary restriction in humans is that it can leave you permanently hungry and cold, cause a drop in libido, and require you to spend your entire life thinking about how much and what you’re going to eat. So maybe you could live longer by this method, but what’s the point?
What we would like to do is mimic some of the effects of dietary restriction—but make it work for a normal lifestyle. The science behind concepts like intermittent fasting and the “5:2” diet (eat normal for five days, restrict calories for two) is very interesting, but is not totally there yet. The idea is to trick your body into going into a fasting state without actually having to fast for very long periods of time. One of the things this is thought to do is switch on cellular programs for removing cell damage (although we don’t know how important this is yet).
One of the many benefits of exercise is that it helps turn over mitochondria, use up the food you eat, and keep mitochondria working as you use ATP for your basic energy needs. If you’re consuming too many calories and not getting any exercise, your mitochondria are akin to little couch potatoes: Your food is being funneled to your mitochondria, but you’re not using all of it to make ATP. So the mitochondria is getting huge inputs and not making many outputs.
How exactly exercise benefits mitochondria is not clear at this stage, but we have some theories. If you’re training for a marathon, your muscles get bigger; and inside those muscles, the mitochondria in your muscle cells also increase. It’s likely that the mitochondria are working more efficiently and preventing buildup of lipids and sugars inside your cells. Again, this is a hypothesis—we have a lot more to learn—but it’s plausible that many benefits of exercise reside inside the cell, by increasing the number of mitochondria and using food more efficiently.
Does free radical damage play a role?
“Free radical” is just a way of saying that an electron is unpaired. Electrons in molecules like to be paired up. For example, as food is broken down, electrons can be removed from the molecules and react with oxygen to form reactive oxygen species, which we call “free radicals.” That can cause an unregulated chain reaction, and damage to the membranes and proteins in the cell.
“The traditional view is that free radicals are always bad—and they can certainly cause damage—but now we think that small amounts of free-radical production might be important signals from mitochondria or other parts of the cells that things are actually working well.”
We know that free radicals are produced by mitochondria—they are one of the major sources of free radicals inside the cells. Most of the oxygen we breathe goes to mitochondria, and it’s the oxygen that picks up an electron, becomes a free radical, and then initiates damage.
The traditional view is that free radicals are always bad—and they can certainly cause damage—but now we think that small amounts of free-radical production might be important signals from mitochondria or other parts of the cells that things are actually working well. This might only become an issue if the mitochondria are damaged and produce excessive free radicals. This idea is still being explored.
We do know that in some situations, free radicals produced in dramatic excess can damage mitochondria; for example, in extreme situations like heart attacks or strokes. We think that in those situations—and perhaps in neurodegenerative diseases or inflammation—that by decreasing some of this mitochondrial damage, cells might survive better. There is some animal evidence to support this but it’s still a hypothesis and it will take very large clinical trials before we’re sure.
How did you come to invent MitoQ?
In the 1990’s, I was working at the University of Otago in New Zealand with professor Robin Smith, studying mitochondria.
There was huge interest in antioxidants as a potential protector from oxidative (free radical) damage. But when you look at the clinical trials—on antioxidants like CoQ10, vitamin C, and vitamin E for any diseases, comparing people with normal levels of dietary oxidants to people taking huge levels—the antioxidants didn’t work to cure diseases.
Professor Smith and I were interested in investigating why this might be, and if there was a workaround. Perhaps, we thought, if dietary antioxidants were distributed throughout the body, their benefits were limited, because they’re taken up by different mechanisms around the body. If we had something that could bypass these mechanisms and also accumulate inside mitochondria (where we think a lot of free radical damage occurs), then maybe we would have a better, more useful antioxidant. So we set about creating molecules that could accumulate inside the mitochondria.
It turns out that inside the cell, the mitochondria has a voltage across its membrane, and it uses that voltage, generated by burning fat and sugar, to make energy available. Inside the mitochondria, it’s negatively charged. So we thought that if we had a positively charged antioxidant, it would be attracted to a negative charge. We made particular types of positively charged (lipid-loving) molecules that had the ability to go straight through biological membranes (this is unusual because most charged molecules can’t make it through a membrane). You could eat them and they would go straight through your cell membranes and end up in mitochondria.
First we made mitochondria-targeted molecules, and then we made mitochondria-targeted antioxidants, which became MitoQ. MitoQ utilizes the active piece of CoQ10, which is often used as an antioxidant supplement, but is poorly taken up by the body and doesn’t accumulate in mitochondria.
We worked to get a big accumulation of MitoQ inside the mitochondria, so that the antioxidant could be activated by an enzyme there, block and suck up some of the free radicals, and then be recycled back to its active form.
How has MitoQ been studied?
We’ve looked at MitoQ in a wide range of animal studies, typically on mice and rats who have all kinds of degenerative diseases where we think oxidative damage from mitochondria and free radicals might be a contributing factor, like Alzheimer’s, diabetes, sepsis, and inflammation. Results from these animal models suggest that preventing some of this oxidative damage to mitochondria might help prevent some specific diseases.
MitoQ has also been taken into clinical trials. There was a trial for Parkinson’s disease, which found that MitoQ was safe to take, but not effective at treating Parkinson’s. Unfortunately, this is probably because by the time someone is diagnosed with Parkinson’s, too much damage has been done.
The gold standard will be clinical trials against a placebo: Sometimes people can take something and feel better, but scientifically we don’t know what that means until that thing has been tested in a controlled clinical trial. There are some interesting ongoing human studies with MitoQ:
There are a few trials where we found that MitoQ lowered blood pressure by making arteries distensible, which is an important cardiovascular risk factor associated with aging.
A study by a group at the University of Colorado, Boulder showed giving MitoQ to mice that were already old or middle-aged could reverse damage from high blood pressure. They’re now working on the same trials in humans.
One of the National Institutes for Health, the National Institute for Aging in Baltimore, runs an Interventions Testing Program where they take drugs believed to have some effect on aging, like resveratrol, and they feed them to mice at various ages through their lifespan. They are testing MitoQ now, and they’ll likely report their findings next year.
What else is promising or exciting at your Cambridge lab?
What we’re trying to think about now, in my lab and around the world, is how mitochondrial damage and mitochondrial function can be key targets for developing new drugs. And we ought to think more about how mitochondrial function is affected by exercise and diet—because new science-backed interventions might be simple—and not even involve drugs.
“It’s clear that mitochondrial metabolism is important in all sorts of aspects of health.”
We’re very interested in the idea that mitochondria might help the cell decide how to respond to signals. It’s clear that mitochondrial metabolism is important in all sorts of aspects of health. Here are some potential applications:
With a heart attack, your blood supply stops for a while, so there’s no oxygen getting to the tissue. If the tissue lacks blood and oxygen for enough time, and you end up in the hospital, the doctors will restore blood flow to the heart. The blood coming back into the heart has been deprived of oxygen—and it’s in those few minutes when the un-oxygenated blood comes back in that a lot of damage happens. So ironically, you restore the heart by putting blood back in, but the very act of putting blood back in it causes damage. We’d like to figure out how that process might cause less damage, so patients can recover better. What we’re finding is that some of the metabolites from food seem to build up and potentially drive damage when the blood is coming back in—we’re exploring how that could occur and what role exactly mitochondrial metabolism might play.
We’re also trying to understand how mitochondria might be important in signaling inflammation and regulating how the cell responds to infections where you have damaged tissue. We think there is a big switch in how mitochondria work when they respond to an infection or damage. If we can understand how mitochondria are involved in responding to infection, we can potentially block some excess inflammation.
Another area of great interest at the moment is cancer. We know that in cancer, mitochondrial metabolism is dramatically altered, but we don’t totally understand the reasons why. It seems that changes in mitochondrial function are used to help cancer cells replicate and grow. This might lead to a potentially important target for new therapies in cancer.
If we can understand mitochondria better in the context of these diseases, we can better understand the signals and feedback messages they exchange with the rest of the cell. Understanding all the mechanisms behind these processes, how exactly mitochondria work, how damage inside the cell is turned over, and so on, could give us interventions to not just extend life, but to extend the healthspan—to keep people healthier longer.
Mike Murphy received his B.A. in chemistry at Trinity College, Dublin in 1984 and his Ph.D. in Biochemistry at Cambridge University in 1987. After stints in the US, Zimbabwe, and Ireland he took up a faculty position in the Biochemistry Department at the University of Otago, Dunedin, New Zealand in 1992. In 2001 he moved to the MRC Mitochondrial Biology Unit in Cambridge, UK (then called the MRC Dunn Human Nutrition Unit) where he is a group leader. Murphy’s research focuses on the roles of reactive oxygen species in mitochondrial function and pathology. He has published more than 300 peer-reviewed papers.
The views expressed in this article intend to highlight alternative studies and induce conversation. They are the views of the author and do not necessarily represent the views of goop, and are for informational purposes only, even if and to the extent that this article features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment, and should never be relied upon for specific medical advice.