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I.R.F. / Survey / Chapter 2

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Aging, The Molecular Concepts


Each human cell contains hundreds of mitochondria, and thousands of mtDNAs. The mtDNAs are maternally inherited and accumulate base substitution and rearrangement mutations much faster than nDNA. When a new mtDNA mutation arises in a cell, a mixed intracellular population of mutant and normal mtDNA molecules is generated, known as heteroplasmy. As the heteroplasmic cell replicates, the mutant and normal mtDNAs are randomly distributed into daughter cells. Consequently, over many cell divisions, the mutant and normal mtDNAs segregate out, resulting in cells with a pure population of mutant or normal mtDNAs (homoplasmy). As the percentage of mutant mtDNAs increases by this "replicative segregation", the energy-generating capacity of the cell or tissue declines. Since each tissue has a characteristic mitochondrial energy requirement, its "bioenergetic threshold", as mitochondrial energy capacity declines, organ-specific thresholds are transversed and symptoms appear and become progressively worse. Empirical evidence indicates that the CNS is the most highly reliant on mitochondrial energy, followed by heart, skeletal muscle, kidney, endocrine system and liver (15-18).

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