CHRONIC FATIGUE, MITOCHONDRIAL FUNCTION AND DEGENERATIVE DISEASE
When mitochondrial function is impaired, the net energy available to cells is limited to the Krebs Cycle and anaerobic metabolism. There are a number of conditions and substances that can impair mitochondrial function, but oxidation and damage of mitochondrial lipids in membranes are thought to be among the most important causes.Oxidation of membrane lipids results in modification of membrane fluidity and the electrical potential barrier across mitochondrial membranes, essential elements in the proper functioning of the electron transport chain. Mitochondrial function appears to be directly related to fatigue, and when patients experience fatigue their mitochondrial function is inevitably impaired. Fatigue is a complex phenomenon determined by several factors, including psychological health. At the biochemical level fatigue is related to the metabolic energy available to tissues and cells. Thus the integrity of cellular and intracellular membranes, especially in the mitochondria, is critical to cell function and energy metabolism. When mitochondrial membrane glycophospholipids, phospholipids, fatty acids, and other essential lipids are damaged by oxidation, they must be repaired or replaced in order to maintain the production of cellular energy to alleviate fatigue.
The decline of cellular energy production with aging appears to be due, in part, to mitochondrial lipid peroxidation by ROS and the failure to repair or replace damaged molecules at a rate that exceeds their damage. Membrane damage and subsequent mitochondrial dysfunction by ROS can also lead to modifications (especially mutations and deletions) in mitochondrial DNA (mtDNA). The mitochondrial theory of aging proposes that the development of chronic degenerative diseases is the result, in part, of accumulated mtDNA mutations and deletions and oxidative damage to mitochondrial membranes over time.Indeed, these studies have linked the development of certain chronic diseases with the degree of mitochondrial membrane lipid peroxidation and mtDNA damage. Thus the damage to mtDNA and mitochondrial membranes seems to be involved in the etiology of age-associated degenerative diseases leading to changes in the expression of genes important for cell survival as well as those that control aging. Restoration of mitochondrial membrane integrity, fluidity and other properties are essential for the optimal functioning of the electron transport chain and oxidative generation of ATP and NADH. Declines in energy production with aging and disease coupled with increases in oxidative stress can change gene expression programs and activate cellular apoptosis programs. Apoptosis can also be attenuated with the administration of n-3 polyunsaturated fatty acids.
The ability to control membrane lipid peroxidation and DNA damage likely play a major role in the aging process and the development of age-related degenerative diseases.LRT has proven to be a valuable tool in helping maintain mitochondrial function, and along with combined antioxidant use LRT should be an important part of anti-aging strategies as well as strategies used to treat various age-associated degenerative diseases and conditions.See more info at:
Lipid Replacement as an Adjunct to Therapy
http://www.researchednutritionals.com/information.cfm?ID=24
