Connecting Mitochondrial Biogenesis and Aging

Boosting cell function can improve cognitive processes and overall health

Aging is a natural phenomenon in which progressive decline in tissue and organ function leads to increased risk of disease and mortality. The gradual and progressive structural and functional deterioration of biomolecules in the aging process is associated with many common conditions, including cancer, neurodegenerative diseases, sarcopenia (loss of muscle mass) and liver dysfunction.

Regular exercise and a healthy diet boosted by supplements is known to aid with sleep, energy, memory and other issues affecting both aging and other populations. Through understanding how the health of mitochondria — the power plant of the cell — relates to aging, consumers can choose natural supplements that contain ingredients that may help to improve mitochondrial function. Impaired mitochondrial function is considered a major characteristic of growing old, because mitochondria contribute to specific aspects of the aging process, including cellular senescence, chronic inflammation, and the age-dependent decline in stem cell activity. Studies suggest that mitochondrial energy can influence or regulate several key aspects of aging and by applying strategies directed at improving mitochondrial quality and function, it might have far-reaching beneficial effects, further highlighting the correlation between mitochondrial function and aging.

Mitochondria and aging

Every cell has a herd of mitochondria, which divide like bacteria in a process known as mitochondrial biogenesis. A healthy rate of mitochondrial biogenesis is crucial for maintaining healthy mitochondria, and therefore cells, with age. When damaged, mitochondria are removed, a function of cell activity known as mitophagy. This quality-maintenance mechanism that facilitates the removal of damaged mitochondria from the cell is particularly important to forestalling aging and keeping cells healthy.

Dysfunctional regulation of mitochondrial processes contributes to oxidative stress and cell death during the aging process. With advancing age, all of a cell’s mitochondria may become damaged and can cause significant harm. The capacity for mitochondrial biogenesis also diminishes with age, which is an important parameter in the mitochondrial dysfunction associated with aging (Fannin et al., 1999; Sugiyama et al., 1993). Further research has found that the decline in mitochondrial turnover caused by reduced mitochondrial biogenesis and inefficient mitochondrial degradation seems to be a particularly crucial factor in the aging process (Terman et al., 2010).

Several theories have been proposed to explain the fundamental mechanisms mediating age-related diseases and conditions, but the free-radical theory of aging is by far the most popular. This theory proposes that cumulative damage to biological macromolecules by oxygen radicals leads to irreversible cell damage and an overall functional decline (Harman, 1956). The free-radical theory has been extended to include mitochondria, as the accumulation of aging-associated mutations and deletions in mitochondrial DNA can impair the function of the respiratory chain and enhance ROS production (Chomyn and Attardi, 2003; Harman, 1972). The results of the loss of plasticity in organelles can be cellular senescence, chronic inflammation and decline in stem cell activity.

Activating mitochondria

That mitochondrial function declines with age, and that properly functioning mitochondria are crucial for longevity and minimizing age-related diseases are irrefutable facts. Thus, strategies directed at improving mitochondrial quality and function can have far-reaching health benefits.

Pyrroloquinoline quinone (PQQ) is a small quinone molecule that is widely recognized as an important nutrient in mammals and as a compound that can activate mitochondrial biogenesis, which means it can increase the number of mitochondria in cells. Although it is not biosynthesized in mammals, trace amounts of PQQ have been found in human and rat tissues because of its wide distribution in dietary sources, like fruit and human breast milk.

MGCPQQ® is a natural source of pyrroloquinoline quinone created in Japan by Mitsubishi Gas Chemical Co., Inc. using a proprietary fermentation process that has been well-studied and documented through scientific research and peer-reviewed literature. Its functions have been fully characterized and widely tested in approximately 1,000 animal and human studies over the course of three decades. Studies conducted using MGCPQQ, known as BioPQQ® in the United States, Canada and Japan, show that PQQ may help maintain heart and brain health, and have anti-oxidative and neurogenerative effects, (Stites T., Stomes D., Bauerly K. & Harris C., et al, 2006).

Research shows that MGCPQQ reinforces all functions of mitochondria in the cell. The ingredient increases the NAD+/NADH ratio, promoting the conversion of lactic acid into pyruvic acid to activate mitochondria. It also induces deacetylation of PGC1-α, enhancing the biogenesis of mitochondria. (Saihara K., Kamikubo R., Ikemoto K., Uchida K., Akagawa M., 2017). Dietary MGCPQQ supplementation has been revealed to enhance mitochondrial function and biogenesis and improve metabolic homeostasis in mice and rats, and its function and efficacy has been studied in double-blinded human clinical trials.

One randomized, placebo-controlled, double-blinded study examined the effect of MGCPQQ on cognitive functions in 41 healthy, elderly subjects. The subjects were orally administered 20 mg of PQQ per day or a placebo for 12 weeks. The study measured cognitive function by monitoring selective attention using the Stroop and reverse Stroop tests, which measure subjects’ ability to name the color of an incongruent stimulus – for example, the word “green” written in red. The subjects’ visual-spatial cognitive function was also measured using a laptop tablet. In the Stroop test, the MGCPQQ group performed significantly better than the placebo group. In the Touch M test, the stratification analyses dividing each group into two groups showed that the score significantly increased in the lower group of subjects administered MGCPQQ (Akagawa M., Nakano M., Ikemoto K., 2015).

Additional benefits

Another positive effect of MGCPQQ is its enhancement of Nerve Growth Factor (NGF) production. NGF is a protein composed of 118 amino acid residues and is well known as a neurotrophic factor required for the development and maintenance of peripheral sympathetic and sensory neurons. MGCPQQ has shown to have a stimulatory effect on NGF synthesis and secretion. Studies conducted using MGCPQQ support that it can potentially stimulate Nerve Growth Factor (NGF), and that the ingredient may play a role in the growth and recovery of damaged nerves and organs (Murase K., Hattori A., Kohno M. & Hayashi K., 1993). Neurons are susceptible to lethal damage from oxidative stress, and neuronal death is regarded as a causal factor in some cognitive disorders. By functioning as an antioxidant as well as an NGF enhancer, MGCPQQ has shown to inhibit neurotoxicity.

MGPQQ has also shown to have positive effects on stress, fatigue and sleep. In a clinical trial, 17 adult female subjects ingested 20mg of MGCPQQ daily for eight weeks. The subjects were measured for vigor, fatigue, tension-anxiety, depression, anger-hostility and confusion according to the Profile of Mood States-Short Form before and after the eight-week trial. Scores for all six mood states significantly improved following supplementation of MGCPQQ. Subjects were also tested according to the Oguri–Shirakawa–Azumi Sleep Inventory and showed significant improvement in drowsiness at awaking, sleep onset and maintenance and sleep duration (Akagawa M., Nakano M., Ikemoto K., 2015). Studies conducted using MGCPQQ have shown no adverse effects.

Quality and safety

MGCPQQ is generated using a proprietary technology that does not include chemical synthesis, but rather the purification of natural PQQ derived by bacterial fermentation. PQQ may also be produced through synthetic processes, but these processes may use reagents and solvents which are not recognized as food additives or contain hazardous chemicals. MGCPQQ is the only PQQ ingredient backed by robust clinical safety data – supported by Mitsubishi Gas Chemical’s long research history – and each lot of MGCPQQ is tested to ensure it is of food-grade standards.

The ingredient is registered on the European Union’s list of Novel Food Ingredients. MGCPQQ (BioPQQ) has NDI (New Dietary Ingredient) notification from the U.S. Food and Drug Administration (FDA), and GRAS (Generally Recognized as Safe) status. It has also received the Informed-Choice and Informed-Sports supplement manufacturing certification, ensuring that every batch is tested for WADA-banned ingredients and held to the highest safety standard. MGCPQQ (BioPQQ) is certified as a food ingredient by Japan’s MHLW (Ministry of Health, Labour and Welfare).

Although aging is inevitable, a decline in cognition and energy do not have to be. As of 2019, MGCPQQ is available to nutraceutical manufacturers in the European Union. Visit www.biopqq.com and www.mgcpqq.eu to find products and learn more.

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