Cellular and Metabolic Health
6 Tips to Uncouple Mitochondria and Increase the Chance of Living Longer
Enhancing mitochondrial uncoupling via mitogenesis might improve our cellular health and contribute to our lifespan.
Dear Reader,
Mitochondrial uncoupling excites me and gives me hope to improve our health as one of our century's most effective therapeutic interventions. We can use it in our lives by customizing the methods.
This is not a trivial or controversial matter, and the scientific name should not scare you. This concept is critical for our physical and mental health.
According to distinguished scientists, by uncoupling our mitochondria, we might increase our chance of living longer.
Purpose of the Article
This article briefly introduces the concept and hypothesis of mitochondrial uncoupling within the mitogenesis context without going into scientific details. I highlight its importance for health and longevity and offer practical ways to benefit from the effects of mitochondrial uncoupling via six healthy lifestyle habits.
A Brief Introduction to Mitochondrial Uncoupling
I wrote several articles about mitochondria within the context of cellular, metabolic, and neurological health. Mitochondria, as the powerhouse of our cells, are critical for survival. Without these tiny organelles, our bodies cannot generate energy.
One of the breakthroughs of knowledge accumulating in the literature is the value and potential health benefits of mitochondrial uncoupling, attracting the attention of scientists for good reasons.
This paper defines mitochondrial uncoupling as “a dissociation between mitochondrial membrane potential generation and its use for mitochondria-dependent ATP synthesis.”
Mitochondrial uncoupling is a highly complex process and might be challenging to conceptualize by people with no scientific background. However, we don’t need to know the details to benefit from this promising capability of the human body.
In simple terms, since our mitochondria are extremely busy generating energy which is an arduous task for these tiny organelles, they face a serious issue called reactive oxygen species caused by our metabolic rate. Our mitochondria sacrifice their lives to generate energy for our cells.
In layman’s terms, uncoupling simply means that more mitochondria are created to share the load of generating energy.
Medical and pharmacological scientists hypothesize that mitochondrial uncoupling can protect our cells from conditions that favor the production of reactive oxygen species.
This simple yet powerful mechanism significantly impacts our longevity and vitality. In short, mitochondrial uncoupling is implicated in lifespan extension through its effects on metabolic rate and reactive oxygen species production.
This paper on MDPI, “Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases,” shows how mitochondrial uncoupling could be used to treat several human diseases, such as obesity, cardiovascular diseases, or neurological disorders.
There are many preventative and therapeutic benefits of mitochondrial uncoupling. The critical point is to allow our mitochondria to uncouple by giving them the right conditions.
The key mechanism is managed by uncoupling proteins. So any lifestyle change to increase these proteins can be valuable to achieve mitochondrial uncoupling.
By reviewing the literature, I identified six viable options to initiate mitochondrial uncoupling via healthy lifestyle habits that I summarise in subsequent sections.
1 — Create More Ketone Bodies
Scientists have known the benefits of ketone bodies such as acetone, acetoacetate, and beta-hydroxybutyrate. Until recently, these metabolic products were known as alternative energy for the body and brain when we face energy deficiency.
However, the most exciting breakthrough was that ketone bodies, particularly beta-hydroxybutyrate (BHP), act as a signaling molecule, significantly reducing inflammation in the cells.
By leveraging this knowledge and further investigation, scientists noticed that BHP also plays a role in mitochondria coupling.
In fact, they believe that this feature of BHP is more critical than energy for the body as its utilization as an energy source is relatively poor.
I wrote a lot about the value of ketosis for cellular, metabolic, neurological, and mental health. I explained how to enter ketosis using lifestyle habits. Therefore, I won’t repeat them. Instead, interested readers might check the following three articles.
Here’s How to Rewire the Brain by Activating BDNF & β-Hydroxybutyrate.
In addition to fasting and ketogenic diets, there are other ways to increase BHP and support mitochondrial uncoupling. Two well know supplements are MCT oil and ketone salts.
2 — Use Prebiotics, Probiotics, and Postbiotics
Studies indicated that our microbiome constantly interacts with our mitochondria. Therefore, gut health relates to mitochondrial health.
This point also relates to the previous section. While the liver creates ketone bodies, our gut bacteria create short-chain fatty acids such as butyrate, acetate, and propionate.
As documented in this paper on MDPI titled “The Effect of Probiotics on the Production of Short-Chain Fatty Acids by Human Intestinal Microbiome,” informs that:
“Due to their metabolic abilities, intestinal microorganisms enable the transformation of complex nutrients, such as plant cell wall components (cellulose, pectin, hemicellulose, lignin) and mucins into simple sugars that are fermented to form short-chain fatty acids.
Prebiotics, probiotics, and postbiotics can turn specific food from plant sources (e.g., fiber) into short-chain fatty acids. These fatty acids, like ketone bodies, can also contribute to the uncoupling of mitochondria.
Prebiotics are nutrients to feed the microbiome. Probiotics are bacteria living in our gut. And postbiotics are the bioactive compounds created by probiotics when fed with prebiotics.
Gut health and our microbiota are highly complex matters. However, the key points are consuming plants that provide fiber to feed the friendly bacteria and increasing their amount with fermented foods like kefir, which I mentioned in one of my previous articles.
There are many more fermented foods creating postbiotics, including nitric oxide. From my experience, apple cider vinegar with mother, including acetic acid, is an excellent fermented drink that can generate postbiotics.
In summary, the fermentation process produces postbiotics assisting in replicating healthy bacteria, producing postbiotics, and contributing to the decoupling of mitochondria.
3 — Use Polyphenols and Polyamines
Polyphenols and polyamines gained the significant attention of scientists in recent years due to their effects on our cellular health. Even though the field is still at the nascent stage, studies show promising results for longevity and healthspan.
Polyphenols found in plants serve as antioxidants for cells. The most common ones are flavonoids, polyphenolic amides, and phenolic acids. They usually exist in fruits (especially berries), onions, and turmeric. Popular ingredients are quercetin and restveratrol.
For example, this paper in The Journal of Nutritional Biochemistry informs that “Apple polyphenols induce browning of white adipose tissue.”
This paper informs that “Polyamines are polycations that interact with negatively charged molecules such as DNA, RNA, and proteins. They play multiple roles in cell growth, survival, and proliferation. Changes in polyamine levels have been associated with aging and diseases.”
In short, polyphenols and polyamines act as uncoupling agents. Bluezone studies highlight the importance of these agents for longevity. Scientists observed that centenarians in Blue zones consumed a significant amount of polyphenols in their diets.
4 — Increase Melatonin and Glutathione
Even though polyphenols and polyamines are believed to provide antioxidant properties to the body, recent studies indicate that mitochondria mainly use melatonin and glutathione as major antioxidants.
People usually associate melatonin with the sleep-inducing hormone. However, it is also a potent antioxidant preferred by the mitochondria.
This paper informs that “melatonin protects mitochondria by scavenging reactive oxygen species, inhibiting the mitochondrial permeability transition pore, and activating uncoupling proteins. Thus, melatonin maintains the optimal mitochondrial membrane potential and preserves mitochondrial functions.”
This paper confirms that “mitochondrial uncoupling protein is required for efficient photosynthesis.”
Melatonin activates uncoupling proteins.
Our bodies naturally produce melatonin. In addition, some foods include it. One of the most melatonin in food is known as pistachios. Melatonin is also available as a supplement sold over the counter in many countries.
In Australia, we need a prescription for it. I only used melatonin to cure my jetlag, as I documented in an article titled Here’s How Cortisol Plays a Critical Role in Sleep Disturbances.
This paper states that “among the arsenal of antioxidants and detoxifying enzymes existing in mitochondria, mitochondrial glutathione emerges as the main line of defense for the maintenance of the appropriate mitochondrial redox environment to avoid or repair oxidative modifications leading to mitochondrial dysfunction and cell death.”
As Glutathione is a critical and master antioxidant for the body, I posted an article to increase it naturally. Here is the link to the article: Three Tips to Maintain Healthy Glutathione Levels Naturally.
5 — Leverage Near Infrared Light Exposure
For many years scientists believed that light therapies were pseudo-science. They are not anymore, thanks to numerous studies indicating remarkable health benefits of infrared light exposure to our bodies. It is always important to challenge the status quo in science.
A paper in the Journal of Photochemistry and Photobiology informed and explained that red light therapy might increase the number of mitochondria via multiple mechanisms, including mitochondrial uncoupling.
Another paper, "Effect of Near-Infrared Light Exposure on Mitochondrial Signaling in C2C12 Muscle Cells,” concluded that near-infrared light exposure could alter mitochondrial biogenesis signaling and might represent a mechanistic link to the clinical benefits.
Some medical companies created wearable devices that induce near-infrared light to various body parts, including the brain. Some innovative products even attempt to pass this type of light through the skull. There are also infrared saunas bringing mitochondrial health benefits.
As light therapy is comprehensive and the research proliferates, I plan to document my reviews in another article soon.
6 — Try Cold and Heat Exposure
I left this item to the end as thermogenesis significantly impacts mitochondrial health from my experience and observations.
I explained my years of experience with cold and heat exposure to improve my cellular health in an article titled Here’s What Happened When I Experimented with Thermogenesis for Decades.
I used both cold and heat therapy to improve my mitochondrial health, especially to initiate mitophagy.
Since I documented my findings and experience in a report, I won’t repeat them here. Interested readers might check this article titled Here’s How I Initiate Mitophagy and Make My Mitochondria Denser in 7 Steps.
As informed in this paper, acclimatization to cold is known to have large effects on adaptive thermogenesis.
The paper concludes that “human skeletal muscle has the intrinsic capacity for mitochondrial uncoupling. Cold-induced increases in energy expenditure are accompanied by an increase in skeletal muscle mitochondrial uncoupling.”
I also explained how cold exposure could strengthen mitochondria and might turn white fats into brown fats in an article titled Reduce Visceral Fat and Increase Brown Fat with Two Practical Steps.
Conclusions and Takeaways
The growing literature informs that disturbances in mitochondrial function lead to metabolic diseases, neurodegeneration, cardiovascular diseases, and acceleration of the aging process.
Numerous studies indicate that mitochondrial uncoupling can be an alternative therapeutic target in treating obesity and other metabolic disorders.
Mitochondrial uncoupling can be induced via various lifestyle interventions that I summarized in this article.
In addition to these six points, new studies indicate that pure nicotine might also have mitochondrial uncoupling. However, these studies are inconclusive, so I did not add nicotine to my list. Besides, nicotine is an addictive substance that requires diligence.
For example, this paper informs that “taking into account the inhibitory effect of nicotine on OXPHOS, a report describing an uncoupling effect of nicotine observed in brown adipose tissue mitochondria is particularly interesting.”
Numerous studies observe the signaling pathways that contribute to mitochondrial uncoupling. Signals from the metabolic pathway, immune system, endocrine system, and gut are well-documented.
Mitogenesis is an exciting topic that attracts the attention of many scientists. It refers to the process of induction of mitosis in cells allowing them to divide and keep their exact identity. Mitochondrial uncoupling is a well-understood feature of mitogenesis with promising therapeutic potential.
Takeaways
You might consider the following key points to benefit from mitochondrial uncoupling to improve cellular health. These points are not prescriptive. They can be customized based on your needs, goals, and lifestyle with support from qualified healthcare professionals.
1 — Consider ketosis-initiating lifestyles such as time-restricted eating or ketogenic diets with support from qualified healthcare professionals.
2 — With guidance from qualified healthcare professionals, you might add medium-chained triglycerides such as MCT oil from coconut to the diet.
3 — Increase nutrients with prebiotics, probiotics, and postbiotics such as fermented foods.
4 — Consume food with rich polyphenols and polyamines such as berries.
5 — Increase glutathione and melatonin with healthy lifestyle choices.
6 — Consider cold and heat therapy with support from qualified healthcare professionals suiting your needs.
From my experience and reviews, mild ketosis through time-restricted eating, ketogenic diets, and intense workouts might effectively uncouple our mitochondria, reduce their loads, increase energy, and improve our cellular health and overall well-being.
In addition, these nutritional practices can enhance our metabolic flexibility allowing us to easily switch from sugar-burning to fat-burning mode as desired. Studies on mitochondrial uncoupling indicate that ketone bodies are not just energy sources but potent signaling molecules for cellular health.
Like many scientists, I also believe that initiating mitochondrial uncoupling through the summarized healthy lifestyle habits in this article can improve our healthspan and lifespan.
Thank you for reading my perspectives. I wish you a healthy and happy life.
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