The Role of Somatic and Germline Mutations in Aging and a Mutation Interaction Model of Aging
AbstractMutations with a deleterious effect that is expressed after the average reproductive period are not effectively selected against and can accumulate in the germline. A conservative estimate is that at least 1–2% of new deleterious mutations affect some aspect of DNA replication, repair, or chromosome segregation. Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate. This can have an interactive effect, in that it may increase the rate of somatic mutation during an individual's lifetime. The aging individual therefore becomes increasingly mosaic for somatic mutations, which in turn could potentially contribute to the gradual deterioration of biological processes and influence what we experience as senescence. Interventions that reduce somatic and germ cell mutations should, therefore, reduce the aging process in present and future generations.