Mitochondrial biogenesis (renewal) favors replication of high-functioning mitochondria, while the more damaged mitochondria are more subject to mitophagy, mitochondrial death and reabsorption -a form of autophagy. My question: Might exercise and mitochondrial-specific antioxidants possibly protect or even restore mitochondrial number, contents and quality? Can this help us in living a longer healthier life, and perhaps in the fight against prostate cancer?
Mitochondria, oxidative stress, and antioxidant defenses
The "Mitochondrial Theory of Aging" asserts mitochondria, the primary energy producing components of every cell, are strongly involved in production and leakage of destructive reactive oxygen species (ROS), considered as the main pathogenic agent of many aging related diseases, including the progression of cancers. The process damages DNA and all of the machinery of our cells. And leads to destructive inflammation and cell death (autophagy). These two processes, genetic mutations and inflammation, are the two key drivers of cancer progression ("The Hallmarks of Cancer").
Protecting our mitochondria and their functioning is clearly of paramount importance to health, survivorship and longevity. So I am submitting a review of the most important factors with evidence for helping in this endeavor. I hope to review (and not in just a single post) the following available means to promote mitochondrial, cellular and therefore human health:
Part I Exercise. Both aerobic exercise (aka cardiovascular or endurance), and Strength (resistance) training. Both components have very positive impacts on mitochondria.
Part II Nutritional and supplements to protect mitochondria. These include:
1) Coenzyme Q10 (ubiquinone)
2) Pyrroloquinoline quinone (PQQ)
3) Alpha-Lipoic acid (ALA)
4) L-Carnitine
5) NMN: Nucotinamide Mononucleotide
Then perhaps a Part III: Strategies, medications and supplements to help reduce baseline inflammation. Then I should address the opposing concerns, that mitochondrial biogenesis may be an enabler of cancer stem cell proliferation. Let's start now with exercise, beneficial in so many ways.
Exercise and Mitochondrial number, quality and function in aging Impact on Exercise Performance and Cellular Aging
journals.lww.com/acsmessr/F...
"Loss of mitochondria is well known to occur in many muscles with age, but new results indicate that the capacity per mitochondrion can also decline in human skeletal muscles. These changes in mitochondrial capacity were discovered by comparing the mitochondrial functional limit - the muscle oxidative phosphorylation capacity (ATPmax) - with the mitochondrial content (Vv) of the muscle (6). Figure 2 shows that the mitochondrial phosphorylation capacity declined by half between the adult and elderly group in the VL, yet the mitochondrial content dropped only by 25% with age. This greater loss in mitochondrial function than in content points to a 30% reduction in the capacity of each mitochondrion to generate ATP.
"Aging, inactivity and disease cause degradation of mitochondria in number and in oxidative efficiency. Increased MT leakage of ROS accelerates degradation and accumulates mutations and genetic loss in MT. Uncoupling of respiratory chains decreases the amount of energy (ATP) that can be captured from oxidative electron transport chains (ETCs). Respiratory efficiency diminishes. Aerobic capacity declines."
Exercise capacity paralleling reduced mitochondrial capacity can drop by 50% in the elderly compared with young adults. Yet only half of this is due to decreased in mitochondrial content. The other half of the decline, 25% of total function, is due to diminished functioning of the remaining mitochondria. These are attributed to 1) reduced functioning of the Electron-Transport-Chain of oxidative respiration and also to 2) uncoupling of ATP production from the mitochondrial inner membrane proton gradient ("Uncoupling", H+ Leakage).
"Endurance training is well known to improve aerobic function of elderly subjects and increase mitochondrial content and oxidative enzyme activity of aged muscle in humans. A surprising result from our studies is the apparent reversal of energy uncoupling after 6 months of exercise training in elderly muscle. Figure 8 shows a 25% increase in phosphorylation capacity per mitochondrial volume (ATPmax/Vv) with endurance training in elderly VL muscle (6,14). This result was unexpected because the accumulation of irreversible mtDNA mutations is the prevailing hypothesis for the cause of mitochondrial dysfunction with age (27). These mtDNA mutations are thought to result in permanent defects in the ETC that are unlikely to be reversed with exercise training. However, the significant uncoupling measured in vivo in mouse and human skeletal muscle does not fit with mtDNA mutations but rather is consistent with direct oxidative damage to mitochondrial membranes resulting in increased H+ conductance of the IMM."
Decline in skeletal muscle mitochondrial function with aging in humans
ncbi.nlm.nih.gov/pmc/articl...
"Cumulative mtDNA damage occurs in aging animals, and mtDNA mutations are reported to accelerate aging in mice. We determined whether aging results in increased DNA oxidative damage and reduced mtDNA abundance and mitochondrial function in skeletal muscle of human subjects. Studies performed in 146 healthy men and women aged 18–89 yr demonstrated that mtDNA and mRNA abundance and mitochondrial ATP production all declined with advancing age. Abundance of mtDNA was positively related to mitochondrial ATP production rate, which in turn, was closely associated with aerobic capacity and glucose tolerance. The content of several mitochondrial proteins was reduced in older muscles, whereas the level of the oxidative DNA lesion, 8-oxo-deoxyguanosine, was increased, supporting the oxidative damage theory of aging. These results demonstrate that age-related muscle mitochondrial dysfunction is related to reduced mtDNA and muscle functional changes that are common in the elderly."
To be continued. Paul/MB
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