The accumulation of somatic mutations in humans with age

2019-02-12The rate and nature of somatic mutations that accumulate in humans with age have long been subjects of interest for a variety of reasons. These mutations are known to be the basis of cancer and may also be a factor in the process of aging. A detailed profile showing when and where these mutations arise may help explain the occurrence of cancer, assess their role in aging, and offer insights into their mechanisms. ❧ Despite this interest, studying somatic mutations has long been a challenge because it requires single cell sequencing, something that is not possible without cell expansion in culture or DNA amplification, both of which can introduce their own mutations. ❧ In this study, we address this challenge by using individual colon crypts to effectively represent a single stem cell that gave rise to the crypt shortly beforehand. Using these crypts, we study somatic mutations in young, middle aged, and old subjects. Our data suggests that single nucleotide variation (SNV) somatic mutations increase with age throughout life, but the difference between young and middle aged subjects seems to be considerably more than the difference between middle aged and old subjects. Our data also suggests that deletions larger than 3000 bps also increase with age. The mutational profiles are consistent with multiple mechanisms