Caring for Your Mitochondria: A Key to Your Health

Around 2.5 billion years ago, a transformative pact was sealed on our planet. According to the theory of symbiogenesis, single-celled organisms not equipped for oxygen utilization in their metabolic processes incorporated bacteria with this capability. This partnership birthed miniature energy factories within these cells, which we now know as mitochondria.

Despite having resided within our cells for countless eons, occupying roughly a quarter of their volume, mitochondria still retain traces of their bacterial origins, including their own distinct DNA. Recognizing this lineage is vital because it offers insights into their vulnerabilities and how we can provide them with the care they need.

The significance of maintaining healthy mitochondria cannot be overstated. These tiny organelles play a multifaceted role, from fueling our bodies with energy to influencing our immune responses. Scientists posit that mitochondrial dysfunction is at the core of various health concerns, including the aging process, cancer development, cardiovascular diseases, diabetes, Parkinson’s and Alzheimer’s diseases. Even mental health disorders may be linked to aberrations in mitochondrial function.

Mitochondria and Aging

The primary mission of mitochondria is energy production for the body. Just as a factory relies on raw materials and equipment, mitochondria require glucose, fats from our diet, and the oxygen we breathe to fulfill their function. In fact, mitochondria consume a significant 80% of the oxygen we inhale.

The cell processes these raw materials (glucose and fats) into substances that mitochondria can utilize. Mitochondria, in turn, utilize oxygen in a sequence of eight reactions known as the Krebs cycle to generate ATP, a vital energy source for our cells. ATP is instrumental in a multitude of cellular functions, including protein synthesis, carbohydrate and fat storage, and basic life maintenance. Although the body’s ATP stores are relatively modest, around 60 grams, the constant breakdown and regeneration of ATP amount to a daily turnover approximately equivalent to your body weight.

Nevertheless, no mechanism is perfect, and the same holds true for our intracellular ATP factories. As mitochondria convert glucose and oxygen into energy, they produce reactive oxygen species. Due to their instability, these molecules can engage in undesirable reactions, potentially causing damage to cellular structures. Antioxidants, such as active nitrogen compounds or specific proteins, are required to counteract these reactive oxygen species, transforming them into harmless substances.

Ideally, there is a delicate balance between reactive oxygen species and antioxidants. Reactive oxygen species serve useful functions, regulating cellular growth, life, and death, and safeguarding against bacterial growth. An excess of reactive oxygen species can lead to oxidative stress, which results in damage to nearby biomolecules. Mitochondrial DNA is particularly susceptible to this harm, as it contains crucial information for ATP-producing proteins. Oxygen species can react with it, leading to mutations in the mitochondrial genome. As mitochondria replicate in a process similar to bacteria, these defects are perpetuated. Many scientists hypothesize that the accumulation of such mutations is a fundamental driver of the aging process.

A recent groundbreaking study published in Nature provides further insights into the mechanism of aging. Researchers engineered mice with a genetic modification that caused their cells to produce a faulty protein. This protein, which typically copies mitochondrial DNA during mitochondria division, introduced random errors instead of accurate copies. Consequently, mitochondrial mutations accumulated at an accelerated rate in these mice. Although the mutant mice initially appeared normal during birth and adolescence, they quickly exhibited signs of aging: weight loss, hair loss, kyphosis, osteoporosis, anemia, reduced fertility, and abnormal heart enlargement. Sadly, their lives were notably shorter.

Mitochondria’s Influence on Brain Health

The brain stands as the foremost consumer of mitochondrial energy, devouring a remarkable tenfold more oxygen and glucose compared to other bodily tissues. Consequently, any malfunction in mitochondria can lead to neuron loss, triggering neurodegenerative conditions like Alzheimer’s and Parkinson’s disease.

To unravel how mitochondrial dysfunction plays a role in Parkinson’s disease, a team of researchers from the United Kingdom and Germany delved into the mitochondrial and brain health of both healthy older adults and those suffering from Parkinson’s disease. Their approach involved thinly slicing brain tissue and immersing it in a specialized dye. This dye binds to cytochrome C, a vital protein employed by mitochondria in the synthesis of ATP, the cell’s energy currency. Following this, the brain tissue was thoroughly rinsed. Neurons, being colored in a distinct manner, reflected their mitochondrial health: the brighter the color, the more cytochrome C present, and the healthier the mitochondria.

In the case of healthy elderly individuals, the neurons exhibited vibrant coloration, indicative of a plentiful supply of cytochrome C. However, individuals with Parkinson’s disease displayed less intense staining compared to their healthy counterparts. Their mitochondria were deficient in this critical protein, resulting in an inability to effectively convert oxygen and glucose into energy – they were essentially missing the necessary equipment.

This discrepancy raises a fundamental question: why are the mitochondria in Parkinson’s disease patients so inadequately endowed with cytochrome C? Researchers hypothesized that extensive damage to mitochondrial genes might be responsible for this deficit. Essentially, the genetic information was lost, although the precise reasons behind this loss remain unclear. Both healthy and ailing elderly individuals exhibited damaged neurons with incomplete genetic codes. However, Parkinson’s patients had a significantly higher proportion of such neurons, whereas a healthy young individual had none.

The link between mitochondrial health and neuron function can be challenging to investigate in living humans, prompting research on mice. Before delving into that, it’s essential to note that mitochondria derive energy from food and oxygen for ATP synthesis, but not all of this energy is utilized for this purpose. Some of the energy is dissipated as heat to regulate body temperature, while the rest is used to generate reactive oxygen species. Mitochondria employ specific proteins to dissipate energy in the form of heat.

Scientists manipulated these proteins, leading to mice with varying abilities to regulate heat production. Some mice were unable to efficiently synthesize these heat-regulating proteins, while others synthesized them in abundance. Mice lacking the energy-dissipating proteins generated more reactive oxygen species because there was no outlet for the surplus energy. Additionally, these mice exhibited a reduced number of mitochondria in their neurons, causing these cells to sustain more damage while receiving less energy. Subsequently, the researchers exposed these mice to a neurotoxin known to induce neuronal death and Parkinson’s disease. The mice lacking the crucial proteins fell ill much more rapidly.

Mitochondria’s Role in Our Immune System

Long ago, when a bacterium merged with a cell, it gave birth to a mitochondria and initiated a remarkable partnership. Initially, this bacterium likely acted as a guardian for its host cell. It took care of unwanted guests like bacteria and viruses, trapping them within the cell and digesting them using reactive oxygen species. It’s possible that our immune system has its roots in this early collaboration.

Today, mitochondria play a crucial role in ensuring our body can respond swiftly and effectively to injuries. When cells are damaged, they release mitochondrial DNA into the bloodstream. Since mitochondrial DNA bears a resemblance to bacterial DNA, the body recognizes it as a warning signal and triggers an immune response.

Moreover, mitochondria play a vital role in activating our immune cells, like macrophages. When the body signals an intrusion by a pathogen, macrophage mitochondria undergo a transformation from energy powerhouses to military command centers. In this altered state, they cease their usual ATP synthesis and shift their focus entirely to generating reactive oxygen species. These reactive oxygen species serve a dual purpose: they signal the body to initiate its defense mechanisms against the pathogen and, simultaneously, they can directly combat and destroy the invading pathogen.

T cells also have highly active mitochondria. These specialized immune agents scrutinize other cells to ensure they are free from viruses, and if any are found, T cells take swift action to eliminate them. Much like other mitochondria, T cell mitochondria merge and separate, change in shape and size, adapting their energy production process to the body’s demands. During periods of calm, they tend to be longer, functioning more efficiently and generating fewer reactive oxygen species. However, when the body senses a threat, whether from physical injury or another source, T-cell mitochondria fragment, releasing numerous shorter segments of mitochondrial DNA into the bloodstream. At this point, mitochondria ramp up their production of reactive oxygen species, sending a clear signal to the immune system that it’s time to take action.

Mitochondria and Their Connection to Mental Well-being

When faced with psychological stress, a mouse’s T-cells are activated, and its mitochondria undergo fragmentation, a reaction akin to what happens when it’s infected by a virus. If we engineer mice to have permanently active T-cells and fragmented mitochondria, they exhibit signs of anxiety, lethargy, lack of curiosity, and diminished motivation, all classic symptoms of depression. This prompts a compelling question for scientists: could mitochondria be a contributing factor to mood-related issues in humans?

To explore this hypothesis, researchers conducted a study using rats engaged in a competition for social dominance. Rats occupying dominant positions typically displayed lower anxiety levels. The researchers then examined the mitochondria within the nucleus accumbens of the rat brain, a region responsible for regulating emotions and behavior, a role shared with humans. The findings revealed that rats in subordinate positions had impaired mitochondrial function. Furthermore, they possessed fewer proteins essential for converting oxygen and glucose into energy, essentially lacking the necessary equipment for mitochondria to function efficiently. This discrepancy was found to be inherent in their nature.

While it’s unclear whether humans experience the same effects from innate mitochondrial traits as rodents, it’s well-established that stress affects human mitochondria similarly. As an example, when people experience stress – such as being falsely accused of theft or traffic violations and then being compelled to devise a defense strategy within a mere two minutes – the amount of mitochondrial DNA in their blood increases. This increase activates their immune systems, mirroring the response observed in mice.

Assessing the Health of Your Mitochondria

Currently, there is no straightforward test available for the average person to gauge the status of their mitochondria, but scientists are working on developing one. In the meantime, there are two methods that offer a rough insight into mitochondrial function, as explained by Ekaterina Zvorykina, a biologist and physiologist at “University 2035.”

I. Cardiopulmonary Exercise Testing (CPET)

Mitochondrial function can be roughly assessed through ergospirometry, a test commonly performed by athletes. During this test, ECG and oxygen consumption are monitored before and during exercise, often on a treadmill. The analysis of gas exchange is conducted, and the data is then compared to the resting state to calculate a coefficient. If the result deviates from the norm, it may be an indication of overtraining, which indirectly suggests that the mitochondria may not be in optimal condition.

This information can be particularly valuable for individuals who engage in rigorous and frequent training. For most people, though, this test may not be necessary. A less favorable outcome could signal the development of conditions such as cancer or certain chronic diseases, but there are more convenient ways to monitor these issues.

II. Biochemical Testing

For a more precise assessment, biochemical markers can be analyzed, and several tests can be helpful in this regard.

1. Metabolite Analysis: Pyruvate and Lactate
   • Pyruvate: The mitochondria play a crucial role in synthesizing ATP from pyruvate. Pyruvate is an intermediate product in the conversion of glucose into energy. Elevated pyruvate levels in the blood may suggest disturbances in mitochondrial function.
   • Lactate: When oxygen is insufficient for the mitochondria, cells can derive energy from glucose, although it’s less efficient. Mitochondria generate 30-32 ATP molecules from one glucose molecule, while cells without mitochondria produce only 2 ATP molecules. Consequently, the muscles might produce lactate during intense exercise when there’s insufficient oxygen. Athletes often measure lactate levels to gauge their workload and detect signs of overtraining.
2. Amino Acid Analysis: Amino acids are involved in mitochondrial metabolism and can be used as fuel. Elevated levels of alanine, glycine, proline, and threonine in blood and urine could indicate mitochondrial dysfunction.
3. Carnitine Concentration: Fats in our body break down into fatty acids, and these fatty acids must enter the mitochondria, which requires carnitine. An imbalance of carnitine, either a deficiency or an excess, can impact ATP synthesis because fats are a valuable energy source for mitochondria. Blood carnitine levels can be assessed to gauge how efficiently mitochondria process fatty acids.

It’s essential to note that these biochemical tests are primarily designed to identify mitochondrial diseases and are not meant for assessing the mitochondrial status in healthy individuals. The same increase in lactate, for instance, could signify overtraining or a range of different health conditions, including mitochondrial dysfunction.

Boosting Mitochondrial Health: How to Help Your Powerhouses

Mitochondria can sometimes fall into a state of disrepair due to oxidative stress, an overabundance of reactive oxygen species. While there aren’t direct medications for mitochondria, you can support their health by adjusting your lifestyle. Here are the main strategies recommended by biochemist and biohacker Ekaterina Shcherbakova, an author of “Biohacker Nutrition.”

1. Calorie Restriction. Mitochondria benefit from calorie restriction. This diet is the only one known to unequivocally enhance the lifespan of laboratory organisms, from yeast to mice to monkeys. It reduces inflammation, activates autophagy (the natural process for clearing cellular debris), and triggers mitophagy, which eliminates underused mitochondria. Calorie restriction also increases brain-derived neurotrophic factor (BDNF), aiding in the creation of new neurons and synapses. Consequently, it may slow the progression of neuronal death in conditions like Huntington’s, Alzheimer’s, and Parkinson’s. It also reduces the risk of age-related diseases such as cancer, diabetes, and heart disease. Calorie restriction leads to the restoration of cellular antioxidants like glutathione and coenzyme NAD+, which plays a vital role in converting nutrients into energy. This approach also activates Sirtuins, which serve a dual function: they deactivate genes not required during periods of starvation and assist in repairing DNA damage, including damage caused by reactive oxygen species. Starvation is not necessary; a 25% reduction in calorie intake has been shown to be effective, as demonstrated in a study involving overweight but healthy individuals.
2. Provide Vitamins and Antioxidants to Mitochondria. Besides calorie restriction, mitochondria require essential vitamins, trace elements, and antioxidants.
   • B Vitamins: These are necessary for proteins involved in ATP production in mitochondria. A well-rounded diet with minimal processed foods and plenty of whole foods will ensure adequate vitamin intake.
   • Coenzyme Q10: This is essential for ATP synthesis. It can be found naturally in meat and fish.
   • Quercetin: A natural antioxidant that neutralizes reactive oxygen species. Research has shown that it increases mitochondrial biogenesis, which means more mitochondria within cells. You can find quercetin in red onions, dill, and berries.
   • Resveratrol: Known for its potential health benefits in wine and chocolate, it prolongs the lives of yeast, worms, and flies. It activates Sirtuin, a protein associated with the benefits of calorie restriction, and stimulates mitochondrial biogenesis. Consider sources like grapes, blueberries, and peanuts instead of wine and chocolate.
3. Enhance Gut Health with Pomegranates and Nuts. Gut bacteria play a role in mitochondrial health. Some bacteria produce urolithin A, which activates mitophagy – the process of eliminating mitochondria that no longer produce energy but generate reactive oxygen species. These substances that are used by bacteria can be found in fruits like pomegranates and raspberries, as well as in nuts, particularly walnuts. Additionally, a diet rich in fiber, fermented foods, probiotics, and prebiotics supports the growth of these beneficial gut bacteria.
4. Stay Physically Active. Exercise is one of the most effective ways to enhance mitochondrial function. Regular physical activity increases both the quantity and quality of mitochondria within your cells. Muscle contractions require energy, and mitochondria produce ATP, making this a synergistic relationship. As you become more active, your muscle cells adapt to handling more ATP, ultimately increasing energy production. This, in turn, triggers the process of mitochondrial biogenesis, resulting in a higher number of mitochondria in your cells and more ATP production.
5. Diverse Training Methods. Different types of training affect various muscle fibers and, consequently, mitochondria differently. Generally, aerobic training is recommended, as it is sufficient for improving mitochondrial functionality. Long-distance running, swimming, and cycling primarily engage slow muscle fibers and their associated mitochondria. Combining aerobic and anaerobic activities in forms like Sprint Interval Training (SIT) or High-Intensity Interval Training (HIIT) can be beneficial.While anaerobic training was thought to have limited benefits for mitochondria, there is emerging evidence that resistance exercise, such as strength training, stimulates mitochondrial biogenesis in muscles and energy production by mitochondria[1, 2].
6. Rest and Recovery. While exercise is excellent for mitochondria, excessive training can be detrimental. Overtraining may damage muscle cells, leading to atrophy and overtraining syndrome. Exhaustive workouts can also increase the production of reactive oxygen species, which can damage mitochondria. Balancing your exercise regimen with adequate rest and recovery is essential for maintaining mitochondrial health.