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Dr. Evans is the author of the best-selling book, “The Secret Life of Mitochondria.”
In this podcast, we discuss some key highlights about our cellular powerhouses, our mitochondria.
01:29 Dr. Evan’s Journey: His post-doctoral training was with the head of endocrinology and diabetes at Darmouth. He became cognoscente of diabetes treatments. In type 2 diabetes treatments are behavioral, increased exercise and improved nutrition. In the exercise portion, he noted that people lacked energy. Research at the time showed that mitochondrial dysfunction was a contributive cause of insulin resistance and the inability to adequately process fats and high intake of carbohydrates. It had been viewed that mitochondria just produced ATP, cellular energy. Now they were showing a role in controlling the overall second messenger, calcium levels, controlling overall cell lifespan of the entire organism. They continue to be linked to a great many cellular functions and serve as critical components of our cells and tissues.
05:51 Cellular Sex and Suicide: Mitochondria have their own DNA. They can produce 37 proteins and the genes for other molecules. This DNA is inherited from the mother. Mitochondria are sensitive recipients and regulators of signaling molecules, especially calcium. When there is a dysfunction within the cell, too much oxidative stress or too many toxins, often the cell loses the ability to control itself. The mitochondria sense this and can release enzymes that go outside the mitochondria, but within the cell, which can trigger a cascade of events called programmed cell death (apoptosis).
08:31 Apoptosis: Viruses, mutations in nuclear DNA, or a variety of outside forces or changes in the cell stimulates the mitochondria to begin the process. The caspases enzymes released by the mitochondria cause the cell to die.
10:00 Mitochondria DNA: Nuclear DNA in our cells is protected by the nuclear membrane, histones and is governed by epigenetic controls. Nuclear DNA can be repaired. Mitochondrial DNA is more vulnerable to damage, especially from free radicals generated from our energy production within the mitochondria. Mitochondria do not contain the enzymes to repair the mutations that become problematic. We should do everything we can to minimize free radical generation from excess caloric intake.
11:57 Free Radicals: It is only when we have an overabundance of free radicals that they have a negative impact upon the sensitive parts of our cells. They are generated as part of cellular signaling and biochemistry. Excess intake of processed foods or carbohydrates generates high levels of free oxygen radicals and other reactive species. They are unstable molecules that interact with lipids in the mitochondrial membrane or matrix. They can attack mitochondrial DNA and the proteins within the mitochondria. Superoxide dismutase 2, antioxidant enzyme, is the major enzyme that it has to rid itself of free radicals.
13:58 Results of Mitochondrial Damage: It leads to decreased efficiency in the production of energy molecules. As we age, the levels of superoxide dismutase 2 decrease, meaning that the efficiency of energy production decreases from mitochondrial decay.
14:36 Free Radical Theory of Ageing: The theory is that the main component of ageing is the overproduction of free radicals, from metabolism of certain food sources damaging mitochondria and other cellular components. Increasing free radicals has been found to increase ageing. Ageing is a complex process.
15:43 Telomeres: The protective ends of our nuclear DNA shorten with ageing. The enzyme that lengthens and repairs the telomeres is telomerase. As we age, we lose activity in the telomerases. Our nuclear DNA shortens. This is associated with ageing.
16:33 Interventions for Mitochondrial Health: In experimental models aerobic exercise and caloric restriction are tried and true ways to increase the number and efficiency of mitochondria. Aerobic exercise and caloric restriction slow ageing related disease and increase the health span of the organism. There is a convincing link between the number of mitochondria within an organism and the overall health and delay of age related diseases and ageing.
18:24 Optimizing Mitochondria: There are common pathways and biochemical changes with aerobic exercise and caloric restriction. These involve the genetic apparatus, transcription factors and coactivators that stimulate the DNA to produce new proteins involved in the production of new mitochondria.
20:45 Transcription Factors: Three pathways activate the transcription factors. The transcription factor of Dr. Evans’ focus of study is PGC-1 alpha. He calls it the light switch of mitochondrial biogenesis. When it is activated, it stimulates the production of new mitochondria. The AMP kinase pathway, CERT-1 pathway, and nitric oxide pathway converge to influence PGC-1 alpha similar to caloric restriction and aerobic exercise.
23:54 Phytochemcials Impacting PGC-1 Alpha: Nutrients that have been shown to increase the number of mitochondria are lipoic acid, arginine alpha ketoglutarate, and resveratrol, as well as a methylated compound of resveratrol, pterostilbene. Pterostilbene is a concentrated and more bioavailable form of resveratrol found in blueberries.
28:11 Alpha Lipoic Acid: It is an antioxidant recycler. It is a direct antioxidant and can protect the mitochondria from excess free radicals. Alpha lipoic acid indirectly increases glutathione. Alpha lipoic acid can stimulate our bodies to produce antioxidant enzymes through the activation of another transcription factor, NRF2. NRF2 turns on the body’s antioxidant enzymes and phase 2 detox enzymes. Green tea extract, curcumin and other polyphenols can activate NRF2.
31:56 Arginine: Arginine alpha ketoglutarate was originally designed for sports nutrition. Arginine leads to the increased production of nitric oxide. Alpha ketoglutarate is a component of Krebs cycle. By increasing alpha ketoglutarate, glutamine increases. Glutamine slows protein degradation and can stimulate protein synthesis.
35:14 Disease Link to Mitochondrial Dysfunction: Neurological diseases, metabolic diseases, and cancer have been linked to poor mitochondrial function. Most of us could benefit from nutritional and behavioral interventions that promote mitochondrial biogenesis.
36:40 Dr. Evans’ Elevator Pitch: Unless absolutely necessary, reduce the use of prescription drugs and antibiotics. These damage mitochondria the most. Many nutrients enhance mitochondrial function and biogenesis and are found in fruits and vegetables. Intermittent high altitude training has been shown to stimulate AMP kinase, thus is may be stimulating mitochondrial biogenesis.