Reconstructing the lifelong history of cells and tissues via somatic mutation analysis.

During a lifetime, normal cells accumulate thousands of changes in their genome sequence. These changes, termed somatic mutations, have mostly been studied in the context of cancer, but their presence in normal tissues is ubiquitous and widespread. Somatic mutation accompanies the aging process and is influenced by genetic and environmental factors. Differently from gene expression or imaging data, which fluctuate over time, somatic variants are non-reversible marks in the genome and accumulate over time. This property can be exploited to track the history of a cell, from conception to old age, providing information that cannot be acquired via classical histological tissue inspection nor other types of omics data. Mutations can track embryonic development, measure how clones compete in a tissue over time, or report the mutational processes active in cells and tissues throughout life. We discuss selected examples and emphasize how somatic mutation analysis can enable expanding applications at the service of physiology and cell biology, as well as a deeper understanding of the aging process.