Mutation and intracellular clonal expansion of mitochondrial genomes: two synergistic components of the aging...

The foundations of the Mitochondrial mutational theory of aging include two assumptions: the high abundance of mitochondrial mutations and their ability to clonally expand within individual cells. The up-to-date data pertinent to these assumptions is reviewed and semi-quantitative estimates of the frequencies of mutants and intracellular expansions are offered. The incidence of mutations in various aged tissues may be on the order of one mutant per mitochondrial genome copy, and most of the cells are likely to be affected by intracellular clonal expansions of mitochondrial genomes. Thus aged tissue may be considered a mosaic of cells with different mutant mitochondrial genotypes. Interestingly, independent studies show that a wide range of aged tissues presents with a mosaic of cells with different mitochondrial phenotypes. The necessary methodologies are available to explore whether the two mosaics are causally related. The answer apparently is positive in muscle; other tissues, brain in particular, await exploration.