Pathogenic Mechanisms of Somatic Mutation and Genome Mosaicism in Aging

Jan Vijg, Xiao Dong

Research output: Contribution to journalReview articlepeer-review

57 Scopus citations


Age-related accumulation of postzygotic DNA mutations results in tissue genetic heterogeneity known as somatic mosaicism. Although implicated in aging as early as the 1950s, somatic mutations in normal tissue have been difficult to study because of their low allele fractions. With the recent emergence of cost-effective high-throughput sequencing down to the single-cell level, enormous progress has been made in our capability to quantitatively analyze somatic mutations in human tissue in relation to aging and disease. Here we first review how recent technological progress has opened up this field, providing the first broad sets of quantitative information on somatic mutations in vivo necessary to gain insight into their possible causal role in human aging and disease. We then propose three major mechanisms that can lead from accumulated de novo mutations across tissues to cell functional loss and human disease.

Original languageEnglish (US)
Pages (from-to)12-23
Number of pages12
Issue number1
StatePublished - Jul 9 2020


  • age-related disease
  • aging
  • genome mosaicism
  • pathogenic effects
  • somatic DNA mutation
  • transcriptional noise

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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