A search for DNA alterations in the aging mammalian genome

An experimental strategy

Jan Vijg, A. G. Uitterlinden

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

In order to experimentally test the hypothesis that at the basal level senescence is caused by instabilities in DNA, techniques are required that allow the sensitive detection, quantification and characterization of DNA damage and DNA sequence changes in various organs and tissues of naturally aging mammals. In this article a strategy is presented that should allow the analysis of DNA damage metabolism in aging mammals from the original changes in the chemical structure of DNA (DNA damages) via their processing (DNA repair) to the molecular endpoints in terms of gene mutations and DNA rearrangements. With respect to the detection of DNA damage, a short overview is provided of recently emerged biochemical and immunochemical methods that can be applied immediately to study the spectrum of DNA damages in various organs and tissues of aging animals or humans. By contrast, before one is able to study low frequency changes in DNA sequence organization in somatic tissues, formidable problems have yet to be overcome. This is mainly due to the fact that the scale of highly advanced recombinant DNA techniques recently developed is almost totally devoted to the analysis of heritable genetic factors. In order to be able to study low frequency changes in DNA sequence organization in somatic tissues, we have initiated experimental approaches based on recently emerged shuttle vector technology in combination with transagenic mice, and on new electrophoretic separation principles. These approaches and their potentialities for testing somatic mutation theories of aging are discussed.

Original languageEnglish (US)
Pages (from-to)47-63
Number of pages17
JournalMechanisms of Ageing and Development
Volume41
Issue number1-2
DOIs
StatePublished - 1987
Externally publishedYes

Fingerprint

DNA Damage
Genes
Aging of materials
Genome
DNA
Gene Rearrangement
DNA sequences
Mammals
Tissue
Genetic Vectors
Mutation
Recombinant DNA
DNA Repair
Technology
Metabolism
Animals
Repair
Testing
Processing

Keywords

  • Aging
  • Biochemical and immunochemical detection
  • Denaturing gradient gel electrophoresis
  • DNA damage
  • DNA repair
  • DNA sequence changes
  • Shuttle vector
  • Transgenic mice

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Developmental Biology
  • Developmental Neuroscience

Cite this

A search for DNA alterations in the aging mammalian genome : An experimental strategy. / Vijg, Jan; Uitterlinden, A. G.

In: Mechanisms of Ageing and Development, Vol. 41, No. 1-2, 1987, p. 47-63.

Research output: Contribution to journalArticle

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