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Life Extension Magazine

Life Extension Magazine February 2011
Report

Generate Fresh Mitochondria with PQQ
Scientists Discover the “Other CoQ10”

By Perry Marcone
Mitochondrial Function and Longevity: The Definitive Link
Mitochondrial Function and Longevity: The Definitive Link

In cell biology, mitochondria are unique among other cellular components in one vital aspect: they possess their own primitive DNA, distinct from the DNA housed within the cell nucleus that you normally think of as the building block of all living organisms.

Mitochondrial DNA closely resembles bacterial DNA, the result of an evolutionary legacy.55 Biologists believe that at one time our mitochondria existed as separate, highly energetic organisms. Our primordial ancestor cells aggressively engulfed and incorporated these “proto-mitochondria” into their own internal structure. This furnished our cellular progenitors with two powerful evolutionary advantages: it harnessed the ability of proto-mitochondria to produce vast quantities of energy from oxygen—and served to boost cellular longevity.

This simple fact has profound implications for the science of anti-aging.

Why? You already know that cells in your body have the capacity to divide and replicate themselves owing to the presence of nuclear DNA. If mitochondria possess their own DNA, it follows that they should also have the ability to replicate themselves and increase their number within a single human cell.

This turns out to be the case: human cells may house anywhere from 2 to 2,500 mitochondria,56-58 depending on tissue type, nutrition, antioxidant status, and other factors. Put differently, one cell may contain over 1,000 times more mitochondria than another.

The more high-functioning mitochondria in your body, the greater your overall health and longevity. This is no longer a matter of conjecture. A growing number of cell biologists now espouse the theory that mitochondrial number and function determine human longevity.59-61

The problem is that the scientifically validated methods available to spontaneously increase the number of new mitochondria in our aging bodies are exceedingly difficult. To date, the only known ways to reliably stimulate mitochondrial biogenesis—sustained calorie restriction or strenuous physical activity—are far too rigorous and impractical for most aging individuals.

A nutrient with the power to safely trigger mitochondrial biogenesis would naturally mark an extraordinary advance in the quest to halt and reverse cellular aging.

PQQ has emerged as that nutrient.

Cardioprotection

As with stroke, damage in heart attack is inflicted via ischemia-reperfusion injury. Supplementation with PQQ reduces the size of damaged areas in animal models of acute heart attack (myocardial infarction).52 This occurs whether the supplement is given before or after the ischemic event itself.

To further investigate this potential, researchers at the VA Medical Center at UC-San Francisco compared PQQ with metoprolol, a beta blocker that is standard post-MI clinical treatment. Given alone, both treatments reduced the damaged areas’ size and protected against heart muscle dysfunction. When they were given together, the left ventricle’s pumping pressure was enhanced. The combination also increased mitochondrial energy-producing functions—but the effect was small compared with PQQ alone! And only PQQ favorably reduced lipid peroxidation. The remarkable conclusion: “PQQ is superior to metoprolol in protecting mitochondria from ischemia/reperfusion oxidative damage.”53

Subsequent research from the same team has demonstrated that PQQ helps heart muscle cells resist acute oxidative stress.54 The mechanism? Preserving and enhancing mitochondrial function.

Why Your Mitochondria Are Highly Exposed to Lethal Mutation
Why Your Mitochondria Are Highly Exposed to Lethal Mutation

Cell aging occurs as each cell’s ability to reproduce itself inexorably declines. This decline is in turn associated with the gradual degradation and destruction of the DNA complex.

Overlooked in this process is the equally important role of the mitochondria’s robust ability to reproduce as you age.

Just as degradation of the cellular DNA complex ultimately leads to senescence and death, degradation of the mitochondrial DNA complex leads to the death of the mitochondria and the ultimate extinction of the cell—and the “host” organism.

This death spiral of genetic degradation is accelerated in the mitochondria by the very physiological function they must perform. As the nuclear generators responsible for almost all bioenergetic production, mitochondria are the site of enormous oxidative activity. A nearly incalculable number of electrons are constantly flowing within the mitochondria, throwing off an equally enormous number of free radicals. This makes them highly vulnerable to biochemical insults.

There is an additional threat, as scientists have discovered over the past several decades: relative to nuclear DNA, mitochondrial DNA possesses few defenses against free radical damage.62,63

Cellular DNA is protected by numerous “guardian”proteins (histones and repair enzymes) that act to blunt the impact of free radicals. No such repair systems exist to protect mitochondrial DNA.62,63

Cellular DNA also enjoys superior structural defenses. It is housed within a protective double-membrane that separates it from the rest of the cell. This double-membrane is complemented by a dense matrix of filament proteins called the nuclear lamina, a kind of hard shell casing to further buffer DNA from external impacts.

By comparison, mitochondrial DNA is left almost entirely exposed: it attaches directly to the inner membrane where the mitochondria’s electrochemical furnace rages continuously, generating an enormous volume of toxic reactive oxygen species.

Accordingly, mitochondrial DNA mutates at a much higher rate than cellular DNA.64 When you consider that the mitochondria supply at least 95% of the energy required for all physiological processes in your body, the need to maintain the integrity of mitochondrial DNA takes on even greater urgency. All aging humans should take every step to safeguard the genes that regulate healthy mitochondrial proliferation from lethal mutation. This is supported by an abundance of scientific studies linking genetic mutation within the mitochondria to human aging.65-67

PQQ’s extraordinary antioxidant capacity represents a powerful new intervention that may effectively reinforce the mitochondria’s limited defenses.

Summary

Mitochondrial dysfunction has been definitively linked to virtually all killer diseases of aging, from Alzheimer’s disease and type 2 diabetes to heart failure.

Researchers have recorded evidence of greater mitochondrial damage in the brain cells of humans over 70 compared to those in their early 40s. The health and function of these cellular energy generators is now considered so vital that many scientists believe mitochondrial longevity determines overall longevity in aging humans.

In a revolutionary advance, an essential coenzyme called pyrroloquinoline quinone or PQQ has been shown to induce mitochondrial biogenesis—the growth of new mitochondria in aging cells!

While CoQ10 optimizes mitochondrial function, PQQ activates genes that govern mitochondrial reproduction, protection, and repair. PQQ also affords potent cardioprotection and optimal defense against neuronal degeneration. Published studies show that 20 mg of PQQ plus 300 mg of CoQ10 may reverse age-related cognitive decline in aging humans.

PQQ Activates Signaling Molecules
PQQ Activates Signaling Molecules

A team of researchers at the University of California decided to analyze PQQ’s influence over cell signaling pathways involved in the generation of new mitochondria.17

Their work, published in 2010, led to several extraordinary discoveries.

They found that PQQ’s critical role in growth and development stems from its unique ability to activate cell signaling pathways directly involved in cellular energy metabolism, development, and function. Cells undergo spontaneous mitochondrial biogenesis through the effects of three signaling molecules activated by PQQ:

PQQ activates expression of PCG-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha). PCG-1α is a “master regulator” that mobilizes your cells’ response to various external triggers. It directly stimulates genes that enhance mitochondrial and cellular respiration, growth, and reproduction. Its capacity to upregulate cellular metabolism at the genetic level favorably affects blood pressure, cholesterol and triglyceride breakdown, and the onset of obesity.26

PQQ triggers a signaling protein known as CREB (cAMP-response element-binding protein). CREB plays a pivotal role in embryonic development and growth. It also beneficially interacts with histones, molecular compounds shown to protect and repair cellular DNA.27 CREB also stimulates the growth of new mitochondria.

PQQ regulates a recently discovered cell signaling protein called DJ-1. As with PCG-1α and CREB, DJ-1 is intrinsically involved in cell function and survival. It has been shown to prevent cell death by combating intensive antioxidant stress28,29 and is of particular importance to brain health and function. DJ-1 damage and mutation have been conclusively linked to the onset of Parkinson’s disease and other neurological disorders.

These findings shed light on the results of prior studies where a PQQ deficiency in juvenile mice, for example, resulted in elevated plasma glucose concentrations, a 20-30% reduction in the number of mitochondria in the liver, and consequent impairment in oxygen metabolism.23 These are hallmark indicators of mitochondrial dysfunction. Additional animal models also suggested significant alterations in mitochondrial numbers.25 Taken together, these results confirm PQQ’s power to significantly boost mitochondrial number and function—the key to cellular anti-aging and longevity.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at
1-866-864-3027.

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