What the papers say: where is the somatic mutation that causes aging?
It has been proposed that somatic mutations make major contributions to aging. The first paper, based on a gene knock-in mouse, supports a contributory role for mutation in mtDNA in aging, but does not support a damaged-mtDNA-producing-more-damaged-mtDNA hypothesis. The second paper indicates some GC-rich sequences in the nuclear DNA are more sensitive to oxidative damage than mtDNA. As a result, key genes involved in brain function and mitochondrial function are progressively inactivated with age. Failure in these nucleus-encoded mitochondrial genes may be a primary reason for mitochondrial failure in old age.
Driver
Christopher
C
The National Aging Research Institute, Parkville, VIC Australia. c.driver@nari.unimelb.ed.au
D000375:Aging / Q000235:genetics*; D000818:Animals; D001921:Brain / Q000502:physiology; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*
D004259:DNA-Directed DNA Polymerase