Mitochondria, the powerhouses of our cells (bet you haven’t heard that before), play a crucial role in energy production, metabolic health, and overall cellular function. As we get older, the quantity and efficiency of mitochondria decline, leading to reduced energy levels and increased susceptibility to various diseases.
Mitochondrial biogenesis, the process by which new mitochondria are formed within cells, is essential for maintaining optimal cellular energy and function. By promoting mitochondrial biogenesis, we can enhance energy production, improve metabolic health, and increase resilience against age-related decline.
This blog is all about what we can do to make our mitochondria happy and reproduce…so to speak. We will cover various supplements and lifestyle habits that can influence mitochondrial biogenesis, starting with Coenzyme Q10 (CoQ10), a vital antioxidant found in almost every cell of the body.
Co-Q10 (Ubiquinol vs Ubiquinone)
There are two primary forms of CoQ10: ubiquinone and ubiquinol. Ubiquinone is the oxidized form, while ubiquinol is the reduced, active antioxidant form. In the body, ubiquinone can be reduced to ubiquinol and vice versa, depending on the body's needs. Ubiquinol is considered more bioavailable because it is the form that is directly utilized in the body’s antioxidant defense systems, however, ubiquinone is still widely used in supplements due to its stability and the body's ability to convert it to ubiquinol as needed. CoQ10 is also much less expensive.
CoQ10 is closely linked to mitochondrial biogenesis. CoQ10 supports mitochondrial biogenesis by promoting the activity of PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), a key regulator of mitochondrial biogenesis. PGC-1α stimulates the expression of genes involved in energy metabolism and mitochondrial replication. By supporting the function and replication of mitochondria, CoQ10 helps ensure that cells have enough healthy mitochondria to meet their energy needs, which is particularly important in aging and in conditions associated with mitochondrial dysfunction.
Pyrroloquinoline quinone (PQQ)
Pyrroloquinoline quinone (PQQ) is a redox cofactor and powerful antioxidant, particular to mitochondrial function. PQQ is naturally found in various foods, including kiwi, green peppers, parsley, and fermented soybeans, and it is also produced endogenously within the human body. It plays a crucial role in the function of enzymes involved in cellular energy production and redox reactions. One of the unique properties of PQQ is its ability to stimulate the growth and development of new mitochondria!
PQQ’s relationship with mitochondrial biogenesis is primarily mediated through its activation of key signaling pathways that regulate mitochondrial function and growth. One of the primary pathways influenced by PQQ is the PGC-1α pathway. By activating PGC-1α, PQQ promotes the formation of new mitochondria, thereby enhancing the cell’s capacity for energy production. Additionally, PQQ has been shown to upregulate the expression of Nrf2 (nuclear factor erythroid 2-related factor 2), a transcription factor that enhances the expression of antioxidant enzymes, further protecting mitochondria from oxidative stress and improving their function.
Through these mechanisms, PQQ not only supports the maintenance of existing mitochondria but also stimulates the production of new ones, which is particularly beneficial for tissues with high energy demands such as the heart, brain, and muscles. This makes PQQ a valuable nutrient for promoting overall cellular health, combating age-related mitochondrial decline, and, once again, improving conditions associated with mitochondrial dysfunction.
Urolithin A
Urolithin A is a naturally occurring compound derived from the metabolism of ellagitannins, a type of polyphenol found in certain fruits such as pomegranates, strawberries, and walnuts. When consumed, ellagitannins are converted by bacteria in the gut into urolithin A. This compound has gained significant attention for its benefits related to mitochondrial function and cellular health. Urolithin A is known for its ability to induce mitophagy (autophagy for mitochondria), thereby promoting mitochondrial health and improving cellular energy production.
The relationship between urolithin A and mitochondrial biogenesis is particularly intriguing. Urolithin A stimulates mitophagy by activating specific pathways that lead to the removal of dysfunctional mitochondria. This process is crucial for maintaining a healthy population of mitochondria within cells. By clearing out damaged mitochondria, urolithin A allows for the proliferation of healthy mitochondria, effectively enhancing mitochondrial function. Additionally, urolithin A has been shown to activate the AMPK (AMP-activated protein kinase) pathway, which plays a significant role in energy homeostasis and mitochondrial biogenesis. Activation of AMPK leads to the upregulation of that familiar pathway, PGC-1α.Through this pathway, urolithin A not only helps remove damaged mitochondria but also promotes the formation of new, healthy mitochondria.
The combined effects of mitophagy and mitochondrial biogenesis make urolithin A a powerful compound for supporting overall cellular health and energy production. Research suggests that urolithin A supplementation can improve muscle function, enhance endurance, and protect against age-related decline in mitochondrial function. By promoting the efficient recycling of damaged mitochondria and the generation of new ones, urolithin A maintains optimal mitochondrial performance, which is essential for the health and function of high-energy tissues such as muscles and the brain. This positions urolithin A as a promising therapeutic agent for improving metabolic health, enhancing physical performance, and longevity.
Ketones
Ketones are organic compounds produced by the liver during periods of low carbohydrate intake, fasting, or intense exercise. They serve as an alternative energy source when glucose levels are insufficient. The primary ketones in the human body are beta-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone. These molecules can be utilized by various tissues, including the brain, heart, and muscles, for energy.
The relationship between ketones and mitochondrial biogenesis is multifaceted. Ketones, particularly BHB, have been shown to promote mitochondrial biogenesis through several mechanisms. One key pathway involves the activation of…well…probably guessed it, the PGC-1α pathway. BHB in particular activates PGC-1α, leading to the upregulation of genes involved in mitochondrial replication and function. This enhances the capacity of cells to produce energy, especially in tissues with high energy demands such as the brain and muscles.
In addition to promoting mitochondrial biogenesis, ketones also improve mitochondrial function by improving the the efficiency of the electron transport chain. This results in increased ATP production and reduced production of ROS. The antioxidant properties of BHB further protect mitochondria from oxidative damage, supporting their health and longevity. Moreover, ketones have been shown to activate signaling pathways such as the AMPK pathway. Activation of AMPK by ketones enhances the overall energy efficiency of cells and supports the creation of new mitochondria.
The combined effects of ketones on mitochondrial biogenesis and function contribute to their potential benefits in various health contexts. For instance, ketogenic diets and exogenous ketone supplements have been explored for their potential to improve cognitive function, enhance physical performance, and provide therapeutic benefits in conditions associated with mitochondrial dysfunction, such as neurodegenerative diseases and metabolic disorders.
NAD+ Boosters
Nicotinamide Mononucleotide (NMN) is a nucleotide derived from niacin (vitamin B3) that plays a critical role in the production of nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for various cellular processes, including energy metabolism, DNA repair, and cell signaling. NMN is naturally found in small amounts in foods such as avocados, broccoli, and cabbage, and it is also produced within the body. NAD+ levels decline with age, which is associated with decreased mitochondrial function and the onset of age-related diseases. Supplementing with NMN has gained attention for its potential to boost NAD+ levels.
NMN's relationship with mitochondrial biogenesis is closely tied to its role in increasing NAD+ levels. NAD+ is crucial for the function of sirtuins, a family of proteins that regulate mitochondrial biogenesis and overall cellular health. Sirtuin 1 (SIRT1) is activated by NAD+ and plays a significant role in promoting mitochondrial biogenesis through the activation of PGC-1α. By enhancing NAD+ availability, NMN supports the activation of SIRT1 and the subsequent upregulation of PGC-1α, leading to the increased production of new mitochondria and the enhancement of mitochondrial function.
In addition to its effects on mitochondrial biogenesis, NMN also supports mitochondrial function by improving mitochondrial respiration and energy production. Higher NAD+ levels enhance the efficiency of the electron transport chain, leading to increased ATP production and reduced production of ROS, which can damage mitochondria and other cellular components. By promoting efficient energy metabolism and reducing oxidative stress, NMN helps maintain the health and functionality of mitochondria.
Research suggests that NMN supplementation can have various health benefits, including improved physical performance, enhanced cognitive function, and protection against age-related metabolic decline. In animal studies, NMN has been shown to improve insulin sensitivity, increase endurance, and extend lifespan, highlighting its potential as an anti-aging intervention. By supporting mitochondrial biogenesis and function, NMN plays a vital role in maintaining cellular energy homeostasis and promoting overall health and longevity.
Spermidine
Spermidine is a naturally occurring polyamine found in all eukaryotic cells, playing a crucial role in cellular metabolism and growth. It is named after its high concentration in semen but is also present in various foods such as soybeans, mushrooms, aged cheese, and whole grains. Spermidine is involved in several key biological processes, including the stabilization of DNA, RNA, and ribosomes, as well as the regulation of cell growth, differentiation, and apoptosis.
The relationship between spermidine and mitochondrial biogenesis is significant, primarily through its ability to induce autophagy, a cellular process that degrades and recycles damaged cellular components, including mitochondria. Autophagy is essential for maintaining cellular homeostasis and function, and it becomes particularly important for the removal of dysfunctional mitochondria. By promoting autophagy, spermidine helps ensure that damaged mitochondria are efficiently removed, paving the way to produce new, healthy mitochondria through mitochondrial biogenesis.
Spermidine also influences mitochondrial biogenesis directly by modulating key signaling pathways. One of the critical pathways is the activation of the SIRT1 protein, which is involved in the regulation of mitochondrial biogenesis through the PGC-1α pathway. SIRT1 deacetylates and activates PGC-1α, leading to the upregulation of genes involved in mitochondrial replication and function. Through this mechanism, spermidine supports the generation of new mitochondria and enhances mitochondrial activity, contributing to improved cellular energy production and overall metabolic health.
Research on spermidine has shown promising results in various health contexts. Studies have indicated that spermidine supplementation can extend lifespan in model organisms such as yeast, flies, and mice. It has also been associated with improved cardiovascular health, enhanced cognitive function, and reduced incidence of age-related diseases. By promoting autophagy and mitochondrial biogenesis, spermidine helps maintain cellular homeostasis, supports energy metabolism, and protects against the detrimental effects of aging.
Fasting
One of the key benefits of fasting is its impact on mitochondrial biogenesis and function. During fasting, the body undergoes a metabolic switch from glucose metabolism to fat metabolism, leading to the production of ketone bodies, which serve as an alternative energy source. This metabolic switch is associated with increased production of NAD+ (nicotinamide adenine dinucleotide), a coenzyme crucial for cellular energy metabolism and mitochondrial function. Higher NAD+ levels activate sirtuins, particularly SIRT1, which in turn activate PGC-1α. Through this pathway, fasting promotes the formation of new mitochondria and enhances the function of existing ones.
In addition to promoting mitochondrial biogenesis, fasting also induces autophagy, a cellular process that degrades and recycles damaged cellular components, including dysfunctional mitochondria. By clearing out damaged mitochondria, fasting helps maintain a healthy population of mitochondria within cells. This process is crucial for cellular homeostasis and function, particularly in tissues with high energy demands such as muscles and the brain. The activation of autophagy during fasting is mediated by the inhibition of the mTOR (mechanistic target of rapamycin) pathway, which is a key regulator of cell growth and metabolism. Inhibition of mTOR during fasting allows for the activation of autophagy, promoting cellular cleanup and renewal.
Research has shown that fasting can have a range of health benefits beyond mitochondrial health. These benefits include improved insulin sensitivity, reduced inflammation, enhanced cognitive function, and protection against age-related diseases such as cardiovascular disease, diabetes, and neurodegenerative disorders.
Endurance Exercise
Endurance exercise, or aerobic exercise, involves sustained physical activity that increases heart rate and breathing. Activities such as running, cycling, swimming, and rowing fall into this category. Endurance exercise is well-known for its cardiovascular benefits, including improved heart and lung function, increased stamina, and enhanced metabolic health. Additionally, it has a profound impact on cellular and mitochondrial health, promoting mitochondrial biogenesis and overall cellular function.
The relationship between endurance exercise and mitochondrial biogenesis is particularly significant. During endurance exercise, muscles require a substantial increase in energy, which is supplied by ATP (adenosine triphosphate) generated in the mitochondria. To meet this increased energy demand, the body enhances the production of mitochondria in a process known as mitochondrial biogenesis. This process is regulated by several key signaling pathways, including the activation of PGC-1α. Endurance exercise stimulates the production of PGC-1α, thereby promoting the formation of new mitochondria and enhancing the efficiency and capacity of existing ones.
In addition to PGC-1α activation, endurance exercise also enhances mitochondrial biogenesis through the activation of AMPK and SIRT1. AMPK is activated by the increased energy demands and reduced ATP levels during exercise, leading to the stimulation of pathways involved in energy production and mitochondrial biogenesis. SIRT1, activated by the increased levels of NAD+, produced during exercise, deacetylates and activates PGC-1α, further promoting mitochondrial biogenesis. Together, these pathways ensure that the body adapts to the increased energy demands of endurance exercise by boosting the number and function of mitochondria.
Beyond mitochondrial biogenesis, endurance exercise also improves mitochondrial function by enhancing the efficiency of the electron transport chain, leading to increased ATP production and reduced production of ROS. This results in lower oxidative stress and less damage to cellular components, including mitochondria. Additionally, endurance exercise promotes the removal of damaged mitochondria.
Maintaining and enhancing mitochondrial health is crucial for overall cellular function, energy production, and metabolic health. The decline in mitochondrial quantity and efficiency with age underscores the importance of promoting mitochondrial biogenesis through various strategies. Coenzyme Q10 (CoQ10), pyrroloquinoline quinone (PQQ), urolithin A, ketones, NMN, spermidine, fasting, and endurance exercise all play significant roles in supporting mitochondrial biogenesis and function. These supplements and lifestyle habits activate key pathways such as PGC-1α, AMPK, and SIRT1, leading to the formation of new mitochondria and the removal of damaged ones. By incorporating these practices, we can enhance our cellular energy production, improve metabolic health, and increase resilience against age-related decline, ultimately promoting longevity and overall well-being.