Published in

Frontiers Media, Frontiers in Aging, (2), 2021

DOI: 10.3389/fragi.2021.802407

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The Dynamics of Somatic Mutagenesis During Life in Humans

Journal article published in 2021 by Freek Manders ORCID, Ruben van Boxtel, Sjors Middelkamp
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Data provided by SHERPA/RoMEO

Abstract

From conception to death, human cells accumulate somatic mutations in their genomes. These mutations can contribute to the development of cancer and non-malignant diseases and have also been associated with aging. Rapid technological developments in sequencing approaches in the last few years and their application to normal tissues have greatly advanced our knowledge about the accumulation of these mutations during healthy aging. Whole genome sequencing studies have revealed that there are significant differences in mutation burden and patterns across tissues, but also that the mutation rates within tissues are surprisingly constant during adult life. In contrast, recent lineage-tracing studies based on whole-genome sequencing have shown that the rate of mutation accumulation is strongly increased early in life before birth. These early mutations, which can be shared by many cells in the body, may have a large impact on development and the origin of somatic diseases. For example, cancer driver mutations can arise early in life, decades before the detection of the malignancy. Here, we review the recent insights in mutation accumulation and mutagenic processes in normal tissues. We compare mutagenesis early and later in life and discuss how mutation rates and patterns evolve during aging. Additionally, we outline the potential impact of these mutations on development, aging and disease.