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Nuclear Genomic Instability and Aging.

Laura J Niedernhofer1, Aditi U Gurkar1,2, Yinsheng Wang3

  • 1Department of Molecular Medicine and the Center on Aging, The Scripps Research Institute Florida, Jupiter, Florida 33458, USA;

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|June 22, 2018
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Summary
This summary is machine-generated.

Genomic instability, or DNA damage, accumulates with age and may cause aging. Evidence links DNA damage to cellular senescence and age-related diseases, supporting its role as a root cause of aging.

Keywords:
DNA damageDNA damage responseDNA repairagingmutationssenescence

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Area of Science:

  • Gerontology
  • Molecular Biology
  • Genetics

Background:

  • Organismal aging is associated with nuclear genome decay.
  • Increased DNA lesion burden is observed in older mammals compared to younger ones.
  • The causal link between DNA damage and aging remains a significant research challenge.

Purpose of the Study:

  • To examine evidence correlating nuclear DNA damage with the aging process.
  • To investigate the mechanistic pathways through which nuclear genotoxic stress promotes aging.
  • To evaluate the role of DNA damage as a causative factor in aging.

Main Methods:

  • Review of existing scientific literature and studies.
  • Analysis of data from progeroid syndromes with inherited DNA repair defects.
  • Examination of evidence linking DNA damage accrual to cellular senescence and metabolic changes.

Main Results:

  • Studies show a greater burden of DNA lesions in older mammals.
  • Progeroid syndromes demonstrate accelerated aging due to inherited DNA repair defects.
  • DNA damage accumulation correlates with cellular senescence, metabolic alterations, and tissue dysfunction.

Conclusions:

  • The evidence strongly supports a causal role for DNA damage in the aging process.
  • Nuclear DNA damage acts as a nidus, initiating and promoting aging.
  • Genomic instability is a key factor contributing to age-related decline and diseases.