Aging and Mitochondrial Mutations


dr_duane_graveline_m.d._134By Duane Graveline, MD, MPH

Much has been learned recently about the aging process. Research information is now rapidly accumulating pointing to mitochondrial mutations as the principle if not the sole cause of natural aging.

It occurs because of the progressive loss of the ability of our mitochondria to produce high-energy molecules (adenosine triphosphate - ATP) for cell function. We have learned that progressive damage to our mitochondria results from exposure to the so-called free radicals.

These highly reactive chemicals inevitably lead to modifications of mitochondrial lipids, proteins and DNA, known as mutations, and are a consequence of natural aging.

It is strange that the information which has led me to this aging research has been my last 12 years studying the side effects of statin drug use. It should be of interest to most that statins appear to exert their harm on susceptible people by what amounts to causing premature aging.

This is a novel concept which now seems to be the correct one. The statin effect is more than CoQ10 and dolichol impairment, it is direct interference with mitochondrial maintenance, leading inevitably to premature aging with all the well known attributes of the aging process.

Ordinarily the anti-oxidant system is sufficient to overcome this daily oxidative stress but due to the combination of our predetermined genetic make-up, nutrition factors  and exposure to disease, our anti-oxidation capacity, never 100% in its effectiveness, gradually deteriorates as we age.

This allows excess build-up of so-called free radicals, the primary cause of the mitochondrial damage or mutations that accumulate as we age.

There is a natural reduction in CoQ10 synthesis as we age. More and more we become dependant upon dietary sources of this critical substance, especially after the age of 50. It is CoQ10, usually working in conjunction with glutathione, that helps prevent excess reactive oxygen species accumulation, the primary cause of mitochondrial damage.

Think of our mitochondria as frontline warriors in our constant battle to extract energy from our highly oxidizing enviroment while at the same time being oxidized. Anti-oxidants provide that service to our frontline troops.

We have also learned that our ability to create glycoproteins falls off as we age, whether by nutritional lack, genetic pre-destination or diseases. This immensely complex function in each of our cells has a role even in DNA maintenance and when it fails for any reason, provides a loss of our ability to detect and correct DNA errors.

So Mother Nature has bequeathed us with built-in aging guarantors. It is up to us to modify these natural factors where we can, not to prevent death but to prevent premature aging.

We have learned that a surprising number of common supplements are involved in mitochondrial maintenance and repair. This knowledge has supported the development recently of a huge research effort directed at the use of nutritional supplements in attempting to bolster our failing metabolic and anti-oxidation systems.

Every aspect of our energy equation has been studied and thousands of research studies have been done to determine possible benefit from supplementing this or that vital element of oxidative phosphorylation and anti-oxidation pathways.
         
There is no traditional medical pharmaceutical treatment for the prevention and treatment of mitochondrial mutations. Most, if not all, of the relevant compounds are available OTC as nutritional supplements.

Slowing down excessively rapid aging must involve all that nutritional researchers have learned these past few years.

The list of substances found to be relevant to the process of oxidative phosphorylation and anti-oxidation in the human body is extensive: 

Anti-oxidants found useful: Vitamin C, Vitamin E (tocotrienols), Coenzyme Q10, Alpha-Lipoic Acid, N-acetyl cysteine, Carotenoids, Flavonoids, Proanthocyanidins and Selenium.
Important Accessory Molecules: Vitamin B3 (niacin), Vitamin B6 (pyridoxine hydrochloride), Vitamin B12 (cyanocobalamin), Vitamin B2 (riboflavin), Folic Acid (folate), Vitamin D, Melatonin, Magnesium and Zinc
Phosphatidylcholine and related compounds
Glyconutrients
Probiotics

There is no way the average person can look at this list and formulate their personal requirements for mitochondrial repair.  Even medical professionals, after a lifetime of experience, must work hard to convert these elements of metabolism and anti-oxidation into a rational plan for help.

I have taken on the task of selecting a few from this list that most impress me with their potential to help slow down or reverse the natural process of mitochondrial mutations. Much research remains to be done to validate these premises.

1. CoQ10 - Coenzyme Q10 in our blood and tissue has been shown repeatedly to be reduced in the elderly. The reason for this is now thoroughly understood - our natural ability to synthesize CoQ10 falls off rapidly after the age of 50. Our sole source comes from diet, known to be largely deficient in CoQ10.

2. Selenium - only in the past few years has the full spectrum of selenium's role in health been revealed. Mooseman and Behl's review has done much to illuminate its various roles in body function.

3. Glyconutrient supplements - No longer do we consider our sugars as just simple fuel. The effects of these vital sugars on the resulting peptide structure being created in the endoplasmic reticulum and companion piece, the Golgi apparatus, may be significant.

4. Lecithin - Lecithin is a phospholipid found primarily in egg yolks and soy. Of all the  phospholipids, phosphatidylcholine is singularly the most important. The powerful, even miraculous, reports of extensive studies over the past several decades in the U.S. and in Europe have established a firm understanding of its relationship to aging and diseases of old age.

5. Omega-3 (EPA, DHA). This one is easy. We all know about this powerful antiinflammatory / antioxidant found in Fish or Krill oils.

6. Vitamin C, powdered. A powerful anti-oxidant.

7. Tocotrienol - The new and much improved form of vitamin E. Tocotrienols are naturally occurring members of the Vitamin E family derived from the annatto plant. For years they have been overshadowed by the better known tocopherols, which long have made claim to the title, vitamin E.

8. Magnesium - The average American consumes only 40 percent of the recommended daily allowance of magnesium. This has serious consequences, including death, in many people. Magnesium activates 76 percent of the enzymes in the body and many of these enzymes are in the mitochondrial energy equation.

9. L-carnitine - The adult form of carnitine palmitoyltransferase (CPT) II deficiency has been labeled as the most common lipid myopathy in humans. This autosomal recessively inherited disease may be even more prevalent than generally believed due to under-recognition of the disorder.

10.  Alpha Lipoic acid (ALA) -is a vital coenzyme in the mitochondria's Krebs cycle for the production of cellular energy. In the late 1980s, researchers first identified alpha-lipoic acid's powerful antioxidant role. Of special interest was the unique beneficial effect of alpha lipoic acid on other anti-oxidants.

11. Vitamin B2 and B3 - integral to the oxidative phosphorylation role as companions to CoQ10.

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

Updated December 2015

Comments on dietary supplements mentioned in this article have not been evaluated by the United States Food and Drug Administration and are not intended to diagnose, treat, cure or prevent disease.
Information on this page should not be used for diagnosing or treating a health problem or disease.

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