Genome instability: A conserved mechanism of ageing?

Jan Vijg, Xiao Dong, Brandon Milholland, Lei Zhang

Research output: Contribution to journalReview articlepeer-review

Abstract

DNA is the carrier of genetic information and the primary template from which all cellular information is ultimately derived. Changes in the DNA information content through mutation generate diversity for evolution through natural selection but are also a source of deleterious effects. It has since long been hypothesized that mutation accumulation in somatic cells of multicellular organisms could causally contribute to age-related cellular degeneration and death. Assays to detect different types of mutations, from base substitutions to large chromosomal aberrations, have been developed and show unequivocally that mutations accumulate in different tissues and cell types of ageing humans and animals. More recently, next-generation sequencing-based methods have been developed to accurately determine the complete landscape of base substitution mutations in single cells. The first results show that the somatic mutation rate is much higher than the germline mutation rate and that base substitution loads in somatic cells are high enough to potentially affect cellular function.

Original languageEnglish (US)
Pages (from-to)305-315
Number of pages11
JournalEssays in Biochemistry
Volume61
Issue number3
DOIs
StatePublished - Jul 11 2017
Externally publishedYes

Bibliographical note

Funding Information:
Research in the Vijg lab was supported by grants from US National Institutes of Health [grant numbers AG017242, CA180126, AG047200, and AG038072]; and the Glenn Foundation for Medical Research.

Publisher Copyright:
© 2017 The Author(s).

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