Nuclear Genomic Instability and Aging

Laura J. Niedernhofer, Aditi U. Gurkar, Yinsheng Wang, Jan Vijg, Jan H.J. Hoeijmakers, Paul D. Robbins

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

The nuclear genome decays as organisms age. Numerous studies demonstrate that the burden of several classes of DNA lesions is greater in older mammals than in young mammals. More challenging is proving this is a cause rather than a consequence of aging. The DNA damage theory of aging, which argues that genomic instability plays a causal role in aging, has recently gained momentum. Support for this theory stems partly from progeroid syndromes in which inherited defects in DNA repair increase the burden of DNA damage leading to accelerated aging of one or more organs. Additionally, growing evidence shows that DNA damage accrual triggers cellular senescence and metabolic changes that promote a decline in tissue function and increased susceptibility to age-related diseases. Here, we examine multiple lines of evidence correlating nuclear DNA damage with aging. We then consider how, mechanistically, nuclear genotoxic stress could promote aging. We conclude that the evidence, in toto, supports a role for DNA damage as a nidus of aging.

Original languageEnglish (US)
Pages (from-to)295-322
Number of pages28
JournalAnnual Review of Biochemistry
Volume87
DOIs
StatePublished - Jun 20 2018

Fingerprint

Genomic Instability
DNA Damage
Aging of materials
DNA
Mammals
Cell Aging
DNA Repair
Radioactivity
Genome
Momentum
Repair
Genes
Tissue
Defects

Keywords

  • aging
  • DNA damage
  • DNA damage response
  • DNA repair
  • mutations
  • senescence

ASJC Scopus subject areas

  • Biochemistry

Cite this

Niedernhofer, L. J., Gurkar, A. U., Wang, Y., Vijg, J., Hoeijmakers, J. H. J., & Robbins, P. D. (2018). Nuclear Genomic Instability and Aging. Annual Review of Biochemistry, 87, 295-322. https://doi.org/10.1146/annurev-biochem-062917-012239

Nuclear Genomic Instability and Aging. / Niedernhofer, Laura J.; Gurkar, Aditi U.; Wang, Yinsheng; Vijg, Jan; Hoeijmakers, Jan H.J.; Robbins, Paul D.

In: Annual Review of Biochemistry, Vol. 87, 20.06.2018, p. 295-322.

Research output: Contribution to journalReview article

Niedernhofer, LJ, Gurkar, AU, Wang, Y, Vijg, J, Hoeijmakers, JHJ & Robbins, PD 2018, 'Nuclear Genomic Instability and Aging', Annual Review of Biochemistry, vol. 87, pp. 295-322. https://doi.org/10.1146/annurev-biochem-062917-012239
Niedernhofer LJ, Gurkar AU, Wang Y, Vijg J, Hoeijmakers JHJ, Robbins PD. Nuclear Genomic Instability and Aging. Annual Review of Biochemistry. 2018 Jun 20;87:295-322. https://doi.org/10.1146/annurev-biochem-062917-012239
Niedernhofer, Laura J. ; Gurkar, Aditi U. ; Wang, Yinsheng ; Vijg, Jan ; Hoeijmakers, Jan H.J. ; Robbins, Paul D. / Nuclear Genomic Instability and Aging. In: Annual Review of Biochemistry. 2018 ; Vol. 87. pp. 295-322.
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