The Mitochondrial Free Radical Theory of Aging (MFRTA) is one of the leading theories of how aging occurs on a biological level. Defining the molecular events and the pathways of aging are still contentious in the study of biology and medicine. Theories fall into a couple of primary categories - programmed aging and increasing errors in biological processes.1
Programmed theories of aging:
Damage or Error Theories of aging:
Wear and Tear Theory
Rate of Living Theory
Somatic DNA Damage Theory
Free Radicals Theory / Mitochondrial Free Radical Theory
It's likely that some or all of these theories act in the combinatorial fashion to contribute to human aging. In cell and animal models, various interventions that seem to increase lifespan have been viewed in the context of these theories. In particular caloric restriction, and NAD/sirtuin-based biological pathways.2
Since 1956, the free radical hypothesis of aging has suggested that aging may be driven by biological stress and damage that accumulates through free radical molecules. Free radicals are compounds that have an excess of electrons, which can readily react with surrounding molecules. These reactions result in molecular damage to proteins, lipids, and other molecules that make up cells.3
Figure 1. Compounds that are free radicals or can break down into free radical components
In 1997, Aubrey de Grey postulated that differences in mitochondrial proliferation are a major driver of aging. This theory is based on the fact that mitochondria are the site of oxygen based metabolism, and produce many free radicals during this process. Metabolically effective mitochondria produce many free radicals, and if these mitochondria are damaged by them, the cell will clear them out. The cell has mechanisms to clear out defective mitochondria (called the lysosome degradation pathway). However, if certain mitochondria are damaged in their metabolic ability, and generate fewer free radical, but are not identified as defective and destroyed by the cell, they will proliferate. Thus, if these defective mitochondria proliferate within the cell, they will crowd out the more functional mitochondria. And this crowding out is directly leading to cellular aging.4
Figure 2. Mitochondria diagram
However, at present de Grey's theory is as yet unsubstantiated. There hasn't been any data to demonstrate that defective mitochondria accumulate to any great degree, compared to healthy mitochondria.
The mitochondrial free radical theory of aging is well-substantiated and has been developed over the past 50-60 years. However, specifics of the mechanism underlying reactive oxygen species, mitochondrial function, and mitochondrial proliferation, are not fully worked out. In particular, experiments that draw a direct link between mitochondrial free-radical levels/damage, and cell clearance of defective mitochondria, need to be carried out.
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