[00:00] One of the central hallmarks of aging is mitochondrial dysfunction. We've all heard about the mitochondria, the powerhouse of the cell. And without your mitochondria, you can't produce energy. With age, the mitochondria become weaker, more worn out, and they start damaging nearby cells.
[00:14] Because the mitochondria are central to all cellular functions, mitochondrial dysfunction contributes to all other hallmarks of aging. It's like a domino effect. Once the mitochondria fall, so do the other hallmarks.
[00:26] Fortunately, there are ways to remove and repair these broken mitochondria. You can do that via the process of mitophagy or mitochondrial autophagy. It's basically like a quality control process that eliminates young material and worn-out mitochondria.
[00:40] So in this video, I'm going to break down what is mitophagy, why it matters for aging, and the most effective ways to activate it. One of the major causes of aging is thought to be the accumulation of worn-out old cellular debris, especially old mitochondria that are inside cells.
[00:55] Mitovagi is a type of autophagy that is needed to break down dysfunctional or damaged mitochondria. Mitovagi isn't an entity or a specific organelle. It's almost like a spontaneous formation that engulfs the old mitochondria and degrades it inside lysosomes.
[01:10] With age, you see a decline in mitophagy, which has been seen to promote the accumulation of damaged mitochondria and oxidative stress. It's a two-way process. Loss of mitophagy promotes the accumulation of old cell particles, and that accumulation is what reduces mitophagy.
[01:23] autophagy. Metaphagy is also impaired in various pathological conditions, such as neurodegenerative disease, cardiovascular disease, and cancer. With absent or inadequate autophagy, which is one of the new hallmarks of aging itself, you propagate mitochondrial dysfunction, which is another
[01:38] hallmark of aging. So it is a very central process to aging and longevity. Let's talk about the most powerful way to increase metaphagy. Aging contributes to mitochondrial decline, as ATP producing capacity decreases by about 8% per decade in humans. However, this is thought
[01:53] to be more because of physical inactivity rather than aging itself. That's why exercise is the best thing for your mitochondria, both in terms of maintaining mitochondrial efficiency for energy production, but also through the removal of old mitochondria via the process
[02:08] of mitophagy. The key to increasing mitophagy is inducing physiological stress and causing energy depletion in the body. When you're exercising or experiencing calorie restriction, to activate an energy sensor called NMPK.
[02:21] NMPK then leads to the upregulation of autophagy At the same time NMPK is also the key sensor for mitochondrial biogenesis the growth of new mitochondria The most potent signal for AMPK activation comes from high exercise
[02:37] It's either hip cardio or resistance exercise. For example, one human skeletal muscle study found that autophagy activation was dependent on exercise intensity. Low-intensity exercise didn't meaningfully activate autophagy, whereas higher-intensity exercise increased autophagy markers like LC3B2 and was linked to stronger ANPK activation.
[02:57] Another human study compared sprint interval training with moderate-intensity continuous training and found that both increased ANPK activation and autophagy markers. However, sprint training produced a more time-efficient stimulus.
[03:09] Now, this doesn't mean that you should only do high-intensity exercise or all-out exercise. Longer duration, moderate intensity exercise like zone 2 cardio also plays a key role It may not spike AMPK as aggressively in the moment as high intensity exercise
[03:23] But it creates a sustained energy demand Which will still drive mitochondrial turnover over time There's also research that low intensity exercise like zone 2 cardio Is better for mitochondrial biogenesis, the growth of new mitochondria
[03:36] The benefits of HIIT training also plateau after a few weeks whereas you keep getting benefits with low-intensity exercise over several months and years. In practice, here's the best combination of exercise for mitochondrial health.
[03:48] High-intensity training. It sends a strong signal for mytopathy and adaptation. Lower-intensity, longer-duration exercise builds mitochondrial density and efficiency. Daily frequent movement like walking keeps your mitochondria active
[04:01] and prevents mitochondrial dysfunction from inactivity. I want to take a quick break to tell you about the Bond Charge Infra-Sona Blankets, My go-to way of getting 20-minute sauna sessions on the go without needing to spend an hour to warm up a regular sauna.
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[04:30] This is mediated by an increase in body temperature and increased heart rate that mimic a cardiovascular workout, while at the same time improving arterial stiffness, endothelial function, blood flow, immune system function, blood pressure and metabolic health. It doesn't matter if
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[05:03] a 15% discount by heading over to borncharge.com for Shazin Lund and use the code SEAM for 15% discount. Right back to the video. Now let's talk about supplements. There are certain nutrients and supplements that can increase the process of autophagy and mycophagy. The most studied one
[05:18] is Euroleafon A, a gut microbiome metabolite made from compounds in pomegranates, berries and walnuts. In worms and mice, Euroleafon A increases metabology and improves muscle function. The most popular Euroleafon A supplement online is MitoPure. Now, I've made many videos about
[05:33] MitoPure. It's very expensive and the research isn't that good in my opinion. Here's a short overview of that. Number one, MitoPure does increase hamstring strength by 12%, 12%, but that's without exercise. When you exercise, the effects are probably minimal.
[05:48] Mitochlor doesn't have any effect on upper body strength or grip strength. Number three, it has no effect on VO2 peak or peak power output. Number four, it has minor effects on six-minute walking test. Number five, muscle endurance as tested by a muscle contraction test
[06:03] was not seen to result in improvements compared to placebo after four months. Number six, no effect on body composition and fat loss or muscle mass. And number seven, there's conflicting results on information markers, with some studies finding an effect and others not. The claim that URSN-A
[06:18] is a mitophagy activator in humans is based from a study on six individuals who got muscle biopsies. However, the study enrolled 59 people who got MitoPure, so they saw an 80% drop rate in their sampling, which is suspicious, and it's a very small sample size to begin with. Now, I do think
[06:34] that MitoPure and URSN-A are mitophagy activators in humans. It's not a problem to activate mitophagy. Many other compounds do it, and they do it for a lot cheaper price. For example, all different kinds of polyphenols found in foods like coffee, vegetables, nuts, berries, fruit, olive oil, etc.
[06:50] These don't directly clean mitochondria like a drug, but they can activate stress response pathways like AMPK and SIRT1, which are connected to autophagy, mitochondrial biogenesis, and mitophagy. But all of these compounds, including UFNA, are much weaker at increasing mitophagy than exercise.
[07:07] And exercise is a much bigger activator of AMPK. So if you are taking these compounds while you are also exercising, then exercise does probably 90 of the job The reason is because to increase autophagy and to increase metabology you need to experience energy stress And exercise creates that energy stress by depleting your glycogen
[07:26] You can also experience that with fasting. Fasting as well as calorie restriction are powerful ways to increase metaphygy. When you grow without food for a period of time, your body experiences energy stress. Your ATP levels drop and this activates AMPK while suppressing another growth pathway called mTOR.
[07:43] That shift is one of the main triggers for autophagy, including myotophagy. Calorie restriction, even without full fasting, can have similar effects over time. By keeping energy intake slightly lower, you create a mild chronic signal that promotes cellular cleanup.
[07:57] But just like with exercise, more isn't always better. Aggressive or prolonged fasting without proper nutrition can impair your recovery, reduce muscle mass, reduce bone density, and limit mitochondrial rebuilding.
[08:09] So the goal isn't constant energy deprivation, whether with fasting, calorie restriction or exercise. The goal isn't constant overnutrition either, by eating a lot of protein and a lot of calories and not exercising. The key is creating periodic energy stress and cycling between energy abundance and energy
[08:25] scarcity. So to sum it up, the most powerful ways to activate metabolic is high intensity exercise. No supplement or drug comes close to that. The second thing I would add is consuming different kinds of polyphenolic compounds
[08:37] that also activate NMPK and increase the topology. The third point would be periodic energy stress through either daily intermittent fasting or time-restricted eating or some periods of calorie restriction, basically fat loss.
[08:49] You don't need to starve yourself, you don't need to be on a low-calorie diet for the rest of your life, but you do want to lose fat at least every once in a while. And the last part of increasing my topology is taking certain supplements. You run a SNA potentially, but it's very expensive compared to just exercising, right?
[09:02] You can just go for some sprinting drill training that's for free and it gets you more my topology. You can also take some other compounds, berberine, different kinds of polyphenolic compounds, curcumin, ginger, egg, garlic extract, coffee polyphenols, etc.
[09:15] They all can increase the value, but they don't come close to exercise. Mitochondria isn't some sort of exotic hack. It's a basic maintenance system that your body relies on. As you get older, this process becomes less efficient.
[09:27] Your mitopathy levels decline, which then leads to more damaged mitochondria accumulating inside cells. That's a problem. So you need to actively work on removing these mitochondria and building new ones. Alright, thanks for watching. If you want to discover your health percentage and get your roadmap to top 1% of health, then join the community using the link in the description. I'll see you there.