Treatments for the Mitochondrial Theory of Aging

The increase in free radicals and “cytokine” inflammatory immune cells as you age cause progressive damage to your mitochondria.

This process is so pronounced that leading researchers believe it to be the underlying cause of most aging. They see the vicious cycle that starts with your mitochondria becoming dysfunctional as you age– creating more and more free radical and cytokine damage–leading to more and more dysfunction of your mitochondria.

The Stop this Cycle: Increase the Mitochondria’s multiple renewal pathways:

Cellular energy comes from the mitochondria:

Mitochondria in Cell

1. Stimulate Mitochondrial Repair, Building & Renewal Genes:

(Mitochondria have their own set of separate genes)

     A. Increase the “master regulator” of building new & healthy mitochondria:   PGC-1a  

***Exercise 

***Take PQQ (Pyrroloquinoline Quinone) 

***Maximize the eNOS enzyme:  (expression of PGC-1 is regulated by the endothelial NO synthase (eNOS)/NO/cGMP/PGC-1 activation axis. See Use of Amino Acids L-Arginine, Citrulline, and the use of the natural supplement Taurine

***Use any of the supplements below to increase NO, SIRT1, or AMPK and thereby increase PGC-1a

***Take Quercetin to decrease breakdown of PGC-1a   

Mitochondrial Biogenesis Nutrients

(Courtesy of Zymogen)

     B. Stimulate “Autophagy”

Autophagy is the the cell’s trash disposal system to digest large, “baggy,” dysfunctioning mitochondria (Also called “Mitophagy.”) This process replaces the damaged, large, baggy, inefficient mitochondria. Use:

***Dietary Restriction

***Resveratrol,  and/or

***Metformin

2. Stimulate Nrf2: The Mitochondria and Cellular defense system against free radical damage

This genetic “Antioxidant Response Element” can be “switched on” to produce powerful anti-oxidant enzymes: Each enzyme eliminates free radicals at a rate of one million per second. No antioxidant supplement can approach these powerful effects.

Nrf2

Nrf2 Produces glutathione-containing antioxidants GSH, GST’s, GPx’s–as well as Catalase and others. 

Natural substances that stimulate Nrf2 to increase gene production of the ARE (antioxidant response element) include:

***Tumeric (with its active ingredient Curcurmin)

***Cruciferous Vegetables

***Enerolactones

***Resveratrol

***Wasabe

***Protandim–A supplement that combines many herbs that stimulate Nrf2: Clinically demonstrated to protect the cell from free radical damage as it can decrease the level of “lipid peroxides” over time. There are other products combining Nrf2 stimulators as well.

3RESTORE CELL ENERGY IN THE MITOCHONDRIA 

     A. Increase cell energy by increasing NAD+ in the cell with Nicotinamide Riboside: More NAD+ in the cell means not only more energy can be produced for your functioning, but also more energy for the cell to dispose of inefficient mitochondria and build smaller, more efficient mitochondria–Another way of contributing to mitochondrial mitophagy and biogenesis. 

     B. Increase cell energy by decreasing the activity of p38. Reducing this energy-expensive process allows more energy for these other repair processes. Interestingly, the food-derived flavanoid, apigenin, is a powerful inhibitor of CD38.  Treatment of cell cultures with apigenin increased NAD levels in the cells..

Reference: 2012 Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome.

Here is a list of the foods with the highest concentration of apigenin:

Value Per Nutrient Food
13506.20 mg 100 grams Apigenin Spices, parsley, dried
302.00 mg 100 grams Apigenin Parsley, raw
8.71 mg 100 grams Apigenin Peppermint, fresh
5.00 mg 100 grams Apigenin Thyme, fresh
4.61 mg 100 grams Apigenin Celery, raw
3.85 mg 100 grams Apigenin Rutabagas, raw
2.41 mg 100 grams Apigenin Celeriac, raw

C. Increase Cell Energy by providing the supplements that improve the function of the mitochondria.

     A. Supplement with  CoEnzyme Q10, a necessary part of the heart of the mitochondria-the Electron Transport Chain bellow:

     B. Increase cell energy with any of the following other supplements which help the functioning of the mitochondria: Acetyl-L-Carnitine, Resveratrol, Membrane- Phospholipids, Creatine, Alpha-Lipoic Acid, Green Tea, Glucosamine, Omega-3-Fatty Acids, &             N-Acetyl-Cysteine 

Mitochondria Nutrients Great Pic

C. Improve Mitochondrial functioning by Reducing Mitochondrial Free Radicals (ROS & RNS) Damage:

     A. Take 3-5 mg of Melatonin at bedtime. As you see below, Melatonin has multiple beneficial effects on your mitochondrial functioning.

Mitochondria Melatonin

Melatonin permeates cell membranes and scavenges the ROS (“free radicals”) in the cell cytoplasm, mitochondria and nucleus. In the cytoplasm, melatonin maintains GSH homeostasis. Melatonin also regulates the expression of anti-oxidant enzymes, such as glutathione peroxidase (GPx), glutathione reductase (GRd) and superoxide dismutase (SOD), and downregulates pro-oxidant enzymes, such as the NOSs, particularly the iNOS. Melatonin is accumulated in mitochondria at high concentrations, where it scavenges ROS and RNS. Melatonin also protects cardiolipin from oxidation and prevents respiratory chain complexes, as well as mtDNA from free radical attack, thus ultimately protecting the membrane permeability transition (mPT) pore, thus preventing cell apoptosis.

2. Glutathione.

Our glutatatione levels begin to decrease during our 20’s as you see in the graph below. Restoring glutathione levels can help you feel much better and protect you from many mitochondria and cellular damage. 

Some of the more popular routes of administration:

Intravenous GSH (see Appendix: Expert: Dr David Perlmutter)

Liposomal GSH (see  Appendix: Expert: Dr. Tim Guilford)

RGSH (see Appendix)

Oral GSH (see Appendix: Research +/- on Effectiveness)

Precursors of GSH: (see Appendix)

Cellgevity: A New Modified Cysteine Precursor of GSH (see Appendix)

Glutathione deficiency is increasingly recognized as a risk factor in chronic fatigue, coronary artery disease, asthma, neurodegenerative disorders, cognitive-behavioral problems, and various types of cancer.

Dr. Mehmet Oz did several segments on glutathione on his TV program, calling it the “Superhero of Antioxidants.” It has also been called the “Great Protector,” and the “Mother of Antioxidants” with good reason.

In addition to being an antioxidant, glutathione is also a powerful detoxifier

As a detoxifier, glutathione is unparalleled. It binds metals and other toxins and transforms them into compounds that can be excreted in bile or urine. Once bound, these toxins become water-soluble and can be transported out of cells.

However, the binding of toxins to glutathione creates a demand on the body to make new glutathione. Deficiency results when a tissue or system cannot keep pace with the demand.

Because it is the primary organ of detoxification, the liver harbors the body’s largest stores of glutathione, which plays a role in detoxifying environmental pollutants, radiation, drugs, carcinogenic chemicals, and heavy metals.

Glutathione s-transferases (GST) are a group of enzymes that work in concert with glutathione, and they are critical for removal of many toxins. The loss of GST function may contribute to both acute and chronic illnesses (Ashfaq 2008; Chinta 2006).

In discussing the role GSTs with patients, I often refer to them as matchmakers that introduce glutathione to toxins. When the GST for a specific toxin is present, it can facilitate conjugation of the toxin to glutathione very efficiently. When the GST is absent, the likelihood of the toxin-GSH conjugation is diminished.

Glutathione also plays a major role in immune function. (See Appendix for reports of glutathione restoring immune function)

Even more importantly, a recent discovery has been that we can  stimulate our own gene element “Nrf2” (or “Antioxidant Response Element”)–To produce glutathione-containing antioxidants GSH, GST’s, GPx’s, Catalase, and others.

Nrf2

Each enzyme created eliminates free radicals at a rate of one million to one per second every second. No antioxidant supplement can approach these powerful effects. 

Natural substances that stimulate Nrf2 to increase gene production of the ARE (antioxidant response element) include:

Tumeric (with its active ingredient Curcurmin), Cruciferous Vegetables, Enerolactones, Resveratrol, Wasabe, (Protandim and combinations of the above):

Mild Cell Stress and Nutrients stimulate ARE

Nrf2

 

In addition, we can help the body to stimulate your repair and production of the “batteries” of the cells called mitochondria.

I have seen dramatic results by measuring the free radical load before and after the use of certain supplements. Ask your doctor if an AM APEX test or a TBARS test is right for you.
The most accurate test for HEALTH AND AGING ASSESSMENT for free radicals is the TBARS

4. Focus on the other underlying imbalances which are at the root of premature aging:

a) Evaluate the underlying strengths and weaknesses of your body’s systems. Learn how hormone levels can decrease with aging and the importance of monitoring, and in some cases supplementing low levels of key hormones.

b) Understand that with aging, your body begins to produce too few of the enzymes needed to break down the garbage of the cell. From the age of 25 to 34, the levels of your enzymes plummet, and the pancreas can suffer from repeated bouts of inflammation and scarring as it tries to create enough enzymes for not only the food you eat, but also to “clean up” the arteries, lymphatics and organs from their build up of bio-toxins from the vessel and tissue walls.

Your body also picks up a number of microbes, some of which can become chronic companions to your system and wreak havoc without you even knowing it! (See Biotoxins)

Because of the introduction of thousands of new chemicals during the past century, in some cases that cell has not had the time to evolve the proper enzymes to deal with some of the petrochemicals and other environmental toxins. Therefore, your body may need help with detoxification (see Detoxification section)

c)  So the cell debris overwhelms the “lysosome”–Which is the “garbage disposal” of the cell. The cell debris also gets blocked by swelling around the lymphatic vessels–Which are needed to clean the garbage away from the cell.

However, with treatments, your cells can release the garbage. You just need to optimize the other parts of the body that help excrete unwanted waste—Including the gall bladder, liver and other organs. The movement of the lymphatic system will also help release important immune molecules to help your immune system health. Without moving the lymphatics, you may not be able to release the proteins and other waste products, as their valves are easily closed.

d) My goal is to help you prioritize your health needs so you to not have to understand all of this basic science, but instead you can learn the simple concepts and therapies to strengthen the complex workings of the body—I will also help you with explanations and pictures.

e) Detoxification of external toxins in your cells and bodily tissues is important, and it deserves an example to help explain the problem. Here is a picture of how one common and dangerous class of chemicals (“Dioxins”) can use the receptors on your cell membranes (See how the Dioxin bind to your receptor called “AhR” to “highjack” cell functions:

By attaching to your DNA, dioxins change the proteins which are being produced by the cell. This is just one of many toxins that are affecting your body.

Learn our tools which utilize natural substances to block these dioxins from attaching to the receptors of your cells. In addition, natural binders can “stick” to these toxins in the gut and help eliminate them from you body.

Multiple toxins are disturbing the balance and cell environment, and because there are so many toxins in human fat stores and blood, there is no way to know exactly what these toxins are doing.

Therefore, you will benefit the most with an overall plan to reduce the external toxins and restore your cellular health.

Finally, and most importantly, your trust in this information and in your practitioners are one of the most important parts of your healing process.

The exciting discovery of Protandim and testing that demonstrates its effects:

1) Get a TBARS test: Your doctor can measure YOUR baseline TBARS (a measure of your free radical inflammation).
2) If it is high, check one of my websites (www.lifevantage.com/drjohntafel) to learn about what appears to be the most powerful supplement to decrease free radicals: Protandim.
3) Or, if you choose another specific therapeutic technique, measure your TBARS again in 1-4 months to see how it is working.
On my lifevantage website, if you go the 2 minute mark on the ABC video that comes on, you will see pictures of how protandim works for your free radical defense. Whether you are suffering from an illness or just want to optimize your health, you might be surprised at how powerfully Protandim can help your illness, symptoms, and health as it reduces your TBARS level.
Protandim reduces cell aging by an average of 40 percent by reducing inflammatory free radicals and in your body.

One Protandim a day eliminates free radicals at a rate of one million to one per second every second.
None of your antioxidant supplements can approach these powerful effects. Clinical studies show that you can’t possibly ingest enough antioxidants to eliminate the number of free radicals your body makes every day. Due to its tremendous production of antioxidant enzymes, Protandim promotes a healthy immune system, healthy cardiovascular system, a healthy brain, and improved overall wellness.

Nisoli E, Clementi E, Paolucci C, Cozzi V, Tonello C, Sciorati C, Bracale R, Valerio A, Francolini M, Moncada S, Carruba MO. Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide.Science2003299896–899

Nisoli E, Clementi E, Carruba MO, Moncada S. Defective mitochondrial biogenesis: a hallmark of the high cardiovascular risk in the metabolic syndrome? Circ Res2007100795–806.

 

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