Mitochondrial Restoration, Part I
The theories generally focus on the possible mechanisms by which mitochondria can become dysfunctional and contribute to aging and age-related diseases as shown in the schematic in Fig. 6.
Susceptibility of Mitochondrial DNA to Free Radical Damage
A unique property of mitochondria is that they have their own DNA (deoxy-ribonucleic acid). DNA is the stuff of which genes and chromosomes are made. Mitochondrial DNA (mtDNA) is quite different from nuclear DNA (nDNA) in several respects. First, mtDNA is not associated with histones. Histones are positively charged storage proteins around which nuclear DNA is wound (like thread on a spool) which are vital for the protection of DNA. MtDNA lacks this protective mechanism. Second, most of the complex DNA repair mechanisms that correct damage to nuclear DNA are missing from mitochondria. Therefore, mtDNA lacks both protective and repair mechanisms.
Mitochondrial DNA (mtDNA) is located in the mitochondrial matrix, near the inner mitochondrial membrane (where both energy and free radicals are produced). Since mtDNA lacks protective proteins, it is even more vulnerable to free radical attack.
Mitochondrial dysfunction begins with a less-than-perfect electron transport system. Even under ideal conditions, some electrons leak from the electron transport chain. These leaking electrons interact with oxygen to produce superoxide radicals. Because mtDNA is close to the site of the production of superoxide, hydroxyl, or perhydroxyl radicals, and because it lacks protective and repair mechanisms, it is highly susceptible to free radical-induced mtDNA deletions (damage). In fact, the relatively unprotected and unrepaired mtDNA suffers more than ten times the damage that nuclear DNA does. (7,8,16)
Unfortunately, with mitochondrial dysfunction, leakage of electrons can increase significantly, and a vicious cycle can be created (Fig. 10). These electrons (free radicals) can damage the mitochondrial membrane, resulting in a loss of membrane fluidity and alteration in its permeability. This can lead to further mitochondrial dysfunction, disruption of cellular energy production, and accelerated cellular aging. (6)
Lipid peroxide damage to mitochondrial membranes increases in a linear fashion (Fig. 11), and mtDNA mutations increase exponentially with age (Fig. 12). Barrientos speculated that changes in membrane lipid composition could be a cause of age-related decreased membrane fluidity. (17)
Approaches to Resuscitate Aging Mitochondria
Understanding the proposed mechanisms by which mitochondrial dysfunction can contribute to aging and aging related diseases suggests several potential interventions. These include (1) maintenance of optimal Krebs cycle and respiratory chain efficiency, (2)restoration of mitochondrial membrane fluidity, and (3) reduction in deleterious free radical activity.
Many nutrients play indispensable roles in mitochondrial energy production and provide vital antioxidant protection against the free radicals generated by oxidative phosphorylation. The substances in Table I have been shown to have generally positive effects on mitochondrial dysfunction-related conditions in a number of animal and human studies. These substances have alleviated a number of mitochondrial-induced diseases, including Parkinsons disease, diabetes, and fatigue. A growing number of physicians and scientists believe that mitochondrial support nutrients may prove to be helpful for many of the symptoms associated with aging and age-related diseases.
Subsequent issues of Vitamin Research News will discuss the potential mitochondrial bio-energizers listed in Table I in detail.
Some Mitochondrial Bio-Energetic Enhancers
Vitamin B3 (Niacinamide)
Omega-3 fatty acids
Table 1. Mitochondrial bio-energetic enhancers.
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15. De Grey, A. Reductive Hotspot Hypothesis of Aging, R.G. Landes, Austin, Texas, 2001.
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17. Barrientos, A., Casademont, J ., Cardellach, F ., et al. Qualitative and Quantitative changes in skeletal muscle mtDNA and expression of mitochondrial-encoded genes in the human aging process, Biochemical and Molecular Medicine, 1997, 62: 165-171.
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