Damage or Error (Based) Theory of Aging
Mitochondria Damage — Depletion of Cellular Energy
Mitochondria are the cellular organelles within the cells of our body whose membrane is the location of cell respiration and energy metabolism (oxygen metabolism). These small organelles are the principal sites of energy production, and cells have hundreds of them. It is the location for the cascade of redox reactions i.e. the electron transport chain (ETC) of oxygen metabolism and is the source where endogenous free radicals, i.e. reactive oxygen species (ROS) are produced. Cellular energy currency/molecular ATPs are produced as the coupled reactions of ETC known as oxidative phorsphylation which in turn used as energy to drive cell’s metabolism machine..
It has been proposed that aging was partially a result of decreased energy production in the cell’s mitochondria. In the presence of reduced mitochondria function, cells become defective and lack the energy needed to effectively repair mutated or damaged DNA, replenish and renew injured tissue, and retain the efficiency of our body’s other repair, maintenance and defense systems. This theory about the correlation of cell energy depletion and aging have been validated by published scientific studies since its proposal.
How does the mitochondria gradually lose function and become damaged with aging, and in turn depleted the cellular energy source? The Mitochondria Damage Theory postulates that the free radicals from oxidative processes occurring deep within the mitochondria membranes eventually damage the organelle. Once mitochondria are lost to the cell, they cannot be replaced. Since ROS originate in the mitochondrion, and since mitochondria possess their own genome, many advocates of the free radical theory of aging consider that oxidative damage to mitochondria and the mitochondrial DNA (mtDNA) is more important, because ROS produced within mitochondria create a highly oxidative environment that is known to damage mtDNA. A critical enzyme in counteracting the toxicity of these species is superoxide dismutase, which is present in both the mitochondria and cytoplasm of eukaryotic cells. However the level and efficiency of this body’s internal defense and repair mechanism in mitochondria may also decline with age as the case for the cytoplasm superoxide dismutase we have described in free radical theory of aging section.
Mitochondria is an cellular organelle possessing its own genome with DNA resides within mitochondria which is separate from the DNA in the nucleus. Mitochondria DNA (mtDNA) exists in multiple copies, and is also tightly associated with a number of proteins to form a complex known as the nucleoid. Investigators suspect mitochondrial DNA is injured at a much greater rate than nuclear DNA, possibly because of damaging oxygen radicals during metabolism. Adding to its vulnerability, mitochondrial DNA is unprotected by the protein coat that helps shield DNA in the nucleus from damage. Indeed, some evidence exists that under CR oxidative damage to mtDNA is more important than oxidative damage to nuclear DNA. Although, current technology does not appear capable of assessing the true relevance of damage to mtDNA in aging. Interestingly, disruption of the mitochondrial DNA polymerase resulted in an accelerated aging phenotype, for the first time directly implicating the mtDNA in aging. Research has shown that mitochondria DNA damage increases exponentially with age, and as a result, energy production in cells diminishes over time. These changes may in turn cause declines in physiological performance, and may play a role in the development of age-related diseases. Accumulated mtDNA damage play a significant role in age-related diseases and aging. Investigators are examining how much mitochondrial DNA damage occurs in specific parts of the body such as the brain, what causes the damage, and whether it can be prevented.
