From DNA damage to mutations: All roads lead to aging

Research output: Contribution to journalReview articlepeer-review

Abstract

Damage to the repository of genetic information in cells has plagued life since its very beginning 3–4 billion years ago. Initially, in the absence of an ozone layer, especially damage from solar UV radiation must have been frequent, with other sources, most notably endogenous sources related to cell metabolism, gaining in importance over time. To cope with this high frequency of damage to the increasingly long DNA molecules that came to encode the growing complexity of cellular functions in cells, DNA repair evolved as one of the earliest genetic traits. Then as now, errors during the repair of DNA damage generated mutations, which provide the substrate for evolution by natural selection. With the emergence of multicellular organisms also the soma became a target of DNA damage and mutations. In somatic cells selection against the adverse effects of DNA damage is greatly diminished, especially in postmitotic cells after the age of first reproduction. Based on an abundance of evidence, DNA damage is now considered as the single most important driver of the degenerative processes that collectively cause aging. Here I will first briefly review the evidence for DNA damage as a cause of aging since the beginning of life. Then, after discussing the possible direct adverse effects of DNA damage and its cellular responses, I will provide an overview of the considerable progress that has recently been made in analyzing a major consequence of DNA damage in humans and other complex organisms: somatic mutations and the resulting genome mosaicism. Recent advances in studying somatic mutagenesis and genome mosaicism in different human and animal tissues will be discussed with a focus on the possible mechanisms through which loss of DNA sequence integrity could cause age-related functional decline and disease.

Original languageEnglish (US)
Article number101316
JournalAgeing Research Reviews
Volume68
DOIs
StatePublished - Jul 2021

Keywords

  • Aging
  • DNA damage
  • Pathogenic consequences
  • Somatic mutation
  • Transcriptional noise

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Aging
  • Molecular Biology
  • Neurology

Fingerprint

Dive into the research topics of 'From DNA damage to mutations: All roads lead to aging'. Together they form a unique fingerprint.

Cite this