The accrual of somatic mutations has been implicated as causal factors in aging since the 1950s. However, the quantitative analysis of somatic mutations has posed a major challenge due to the random nature of de novo mutations in normal tissues, which has limited analysis to tumors and other clonal lineages. Advances in single-cell and single-molecule next-generation sequencing now allow to obtain, for the first time, detailed insights into the landscape of somatic mutations in different human tissues and cell types as a function of age under various conditions. Here, we will briefly recapitulate progress in somatic mutation analysis and discuss the possible relationship between somatic mutation burden with functional life span, with a focus on differences between germ cells, stem cells, and differentiated cells.
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