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 mtDNA1 in aging, but does not support a damaged‐mtDNA‐producing‐more‐damaged‐mtDNA hypothesis.1 The second paper2 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. BioEssays 26:1160–1163, 2004. © 2004 Wiley Periodicals, Inc.