Mitophagy Explained: How To Support This Essential Process For Healthy Aging

Almost every single modern health problem we face can be traced back to dysfunction at the cellular level. Whether that is autoimmune disease and inflammation or accelerated aging, our cellular health is key for wellbeing and longevity. In fact, improving cellular health is one of our biggest goals in my telehealth functional medicine clinic. By starting at this foundational level, it can help everything else we are doing be more effective when it comes to a person’s health.

But how do you go about supporting something so microscopic? That’s where mitophagy comes in. As your body’s appointed cellular renewal process, it specifically targets the most important aspect of your cells — the mitochondria — to support your overall health as you age. So let’s take a deeper look into what mitophagy is, how the mitophagy pathway functions, and exactly what you can do to increase it.

What is mitophagy?

Mitochondria are often called the “powerhouses” of your cells. They are responsible for taking in nutrients and oxygen and turning them into ATP — your body’s energy source. Each one of your cells has its own life cycle, and over time can become damaged and weak, including the mitochondria itself. While this is a normal part of the aging process, certain lifestyle factors can also speed up this damage. Everything from a poor diet, toxin exposure and chronic stress can contribute to oxidative stress and the production of free radicals that end up damaging our cells. 

And since your cells are considered “the building blocks of life”, damaged cells can result in a multitude of health problems such as heart disease, diabetes, physical signs of aging like wrinkles, Alzheimer’s, Parkinson’s disease, and more. But your body is so perfectly designed, it has its very own system for keeping your cells in check. This is known as mitophagy. Simply put, mitophagy is your body’s process of identifying and cleaning out damaged and dysfunctional mitochondria, playing a vital role in maintaining healthy mitochondrial dynamics. 

What is the difference between autophagy and mitophagy?

While autophagy and mitophagy both involve your cells, they are two distinct processes.

The term autophagy means “self-cleaning” and refers to your body’s ability to clean out all aspects — proteins, organelles, etc. — of old, damaged cells from your system. Mitophagy on the other hand, is a very specific type of autophagy that only cleans out damaged mitochondria. This may seem confusing at first, but mitophagy is really just a more targeted form of general autophagy. 

How does mitophagy work?

Mitophagy is the ultimate example of quality control. The first step in mitophagy is to determine which mitochondria are in need of repair. When damage to the mitochondria occurs, your body’s PINK1 pathway is activated, attracting Parkin proteins that mark the outer mitochondrial membrane that it is ready for destruction. Then, autophagosomes go to work fusing with lysosomes and forming themselves around the mitochondria—often mediated by specific autophagy receptors—to produce enzymes that break down the mitochondria. 

Does mitophagy lead to cell death?

One of the biggest misconceptions around mitophagy is that it can lead to cell death. After all, if the mitochondria is the powerhouse of the cell, it would seem reasonable to assume that cleaning out mitochondria would lead to the death of the entire cell. Thankfully, your body is a lot smarter than that. In fact, mitophagy helps maintain healthy cell function by addressing damage before it gets out of hand.

Cell death only happens if there’s already been too much damage to the mitochondria. In this case, your cell may activate apoptosis — programmed cell death — to mitigate the risk of dysfunction spreading further throughout your body. Ultimately, the goal of mitophagy is to maintain cellular health by only getting rid of what is necessary before it becomes too late for the entire cell.

In fact, when damaged mitochondria don’t get cleaned up through mitophagy, they can turn into so-called “zombie cells”, or senescent cells, lingering in a half-functional state that generates excess oxidative stress and inflammation that eats away at your body’s tissues. Studies have found that this loss of tissue function specifically from senescent cells increases the risk of age-related diseases. (1)

READ MORE: Zombie Cells And Longevity: What You Need To Know

Ways to support mitophagy

Thankfully there are so many ways to support mitophagy that you can easily incorporate into your daily life. There’s no complicated, detailed protocol to follow, just straightforward tools you can utilize to your cellular advantage.

1. Practice intermittent fasting

Giving your body a break from food for extended periods of time is one of the best ways to trigger autophagy. When nutrients are scarce, your body ends up reusing the existing useful cellular resources and discarding the potentially harmful parts. Multiple studies have found that intermittent fasting can significantly boost autophagy and improve overall cellular health. (2)

2. Eat more cellular superfoods

There are so many cellular superfoods that help to improve multiple aspects involved in cellular health including fighting oxidative stress, promoting DNA repair, and positively influencing mitochondria health. A few in particular have been directly linked to increased mitophagy.

• Pomegranates: Rich in ellagitannins, these polyphenols are converted by your gut microbes into urolithins, compounds shown to support mitophagy. (3)
• Matcha: This concentrated form of green tea contains some of the highest amounts of the super-beneficial compound, EGCG, that can activate autophagy-related pathways. (4)
• Turmeric: Curcumin, the main beneficial compound in this vibrant spice, has been shown to promote autophagy. (5)

Try swapping your morning coffee for matcha a few times a week, snacking on pomegranate seeds, and spicing up your next meal with some turmeric. These simple additions can make a big difference!!

3. Target your supplements

While whole food is foundational, supplements can help give your body that needed boost to get to the next level with concentrated dosages of beneficial compounds. These are the supplements with the most research to support their role in increasing mitophagy. 

• Urolithin A: This is the same byproduct that is produced by your gut when you eat certain foods rich in ellagitannins like pomegranates and has been directly linked to activating mitophagy. Since only a small percentage of people can actually convert ellagitannins into usable Urolithin A, supplementation is the best way to take advantage of this nutrient. (6)
• Spermadine: Known for its role in enhancing autophagy, researchers are continuing to learn how it also activates mitophagy by stimulating the PINK1/Parkin signaling pathway. (7)

In addition to supporting mitophagy, it’s also key to support mitochondria health as a whole. That’s why I specifically formulated Longevity RX MitoMultiply to support healthy aging and energy from the inside out. This clinically inspired blend works to fuel your mitochondria, the power plants of your cells, with ingredients that enhance detox, brain function and resilience to help your body stay sharp, strong, and energized.

4. Exercise regularly

Exercise is another one of the top ways to support mitophagy. But not necessarily in the way you may think. When you exercise your body experiences increased energy demand and temporary oxidative stress. While consistent oxidative stress is harmful to your cells, in the temporary, it can signal your body to activate pathways like AMPK and PGC-1a that promote mitochondrial biogenesis — the creation of new mitochondria. This is an essential piece of the cellular health puzzle as it ensures the damaged mitochondria that is cleared out through mitophagy are replaced with new, healthy mitochondria. This team is key when it comes to longevity. (8)

5. Embrace good stress

You may be wondering how stress can be good. I’m not talking about the emotional kind of stress, I’m talking about the physical kind. Similar to exercise, putting your body under small amounts of physiological stress can help your cells adapt, grow in resilience, and create new mitochondria. Cold plunges and sauna sessions are great ways to flex this physical stress muscle and support mitophagy.

LISTEN NOW: Dr. Anurag Singh: How To Enhance Mitochondrial Health, Postbiotics & The Latest Longevity Research

Bringing it all together

As we can see, your cells are constantly assessing, repairing, and adapting. They are making decisions moment by moment about what to keep and what to let go. And if we want to live well now and as we age, it’s our job to help them change for the better. Between practicing intermittent fasting to exercising regularly, there is so much you can do to support mitophagy and overall mitochondrial health without having to overhaul your entire life — but you’ll be thankful for the rest of your life that you started focusing on your cellular health sooner rather than later.

As one of the first functional medicine telehealth clinics in the world, we provide webcam health consultations for people around the globe. 

Photo: Unsplash.com

Sources

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• Jamshed, H., Beyl, R. A., Della Manna, D. L., Yang, E. S., Ravussin, E., & Peterson, C. M. (2019). Early time-restricted feeding improves 24-hour glucose levels and affects markers of the circadian clock, aging, and autophagy in humans. Nutrients, 11(6), 1234. https://doi.org/10.3390/nu11061234
• Tan, S., Yu, C. Y., Sim, Z. W., Low, Z. S., Lee, B., See, F., Min, N., Gautam, A., Chu, J. J. H., Ng, K. W., & Wong, E. (2019). Pomegranate activates TFEB to promote autophagy-lysosomal fitness and mitophagy. Scientific Reports, 9(1), 727. https://doi.org/10.1038/s41598-018-37400-1
• Zhang, S., Cao, M., & Fang, F. (2020). The role of epigallocatechin-3-gallate in autophagy and endoplasmic reticulum stress (ERS)-induced apoptosis of human diseases. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 26, e924558. https://doi.org/10.12659/MSM.924558
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• Faitg, J., D’Amico, D., Rinsch, C., & Singh, A. (2024). Mitophagy activation by urolithin A to target muscle aging. Calcified Tissue International, 114(1), 53–59. https://doi.org/10.1007/s00223-023-01145-5
• Qi, Y., Qiu, Q., Gu, X., Tian, Y., & Zhang, Y. (2016). ATM mediates spermidine-induced mitophagy via PINK1 and Parkin regulation in human fibroblasts. Scientific Reports, 6, 24700. https://doi.org/10.1038/srep24700
• Palikaras, K., Lionaki, E., & Tavernarakis, N. (2015). Coupling mitogenesis and mitophagy for longevity. Autophagy, 11(8), 1428–1430. https://doi.org/10.1080/15548627.2015.1061172