Somatic mtDNA mutations and aging--facts and fancies.
Mitochondria play a critical role in the life of the cell as they control their metabolic rate, energy production and cell death. Mitochondria have long been appreciated as causative to aging. The age-associated respiratory chain deficiency is typically unevenly distributed and affects only a subset of cells in various human tissues, such as heart, skeletal muscle, colonic crypts and neurons. Studies of mtDNA mutator mice has provided the first direct evidence that accelerating the mtDNA mutation rate can result in premature aging, consistent with the view that loss of mitochondrial function is a major causal factor in aging. New, controversial data have arisen from the studies on molecular mechanisms that drive premature aging in mtDNA mutator mice. Our results suggest that the accumulation of high levels of mtDNA point mutations, causing amino acid substitutions, combined with their clonal expansion is probably the main driving force behind premature aging in mtDNA mutator mice.
Kukat
Alexandra
A
Division of Metabolic Diseases, Department of Laboratory Medicine, Karolinska Institute, S-14186 Stockholm, Sweden.
Trifunovic
Aleksandra
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D028361:Mitochondrial Diseases / Q000378:metabolism; D023421:Models, Animal; D018384:Oxidative Stress; D017354:Point Mutation
D004272:DNA, Mitochondrial