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In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
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DNA damage responses in ageing.

Paulo F L da Silva1,2, Björn Schumacher1,2

  • 1Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, Joseph-Stelzmann-Strasse 26, 50931 Cologne, Germany.

Open Biology
|November 21, 2019
PubMed
Summary

Organismal longevity relies on cellular function and stress response. Therapies targeting these mechanisms, including DNA repair and cellular senescence, may extend healthy lifespan and combat age-related diseases.

Keywords:
DNA damage responseDNA repairageingcellular senescencelongevity

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Area of Science:

  • Gerontology
  • Molecular Biology
  • Cellular Biology

Background:

  • Ageing is a universal biological process affecting all life forms.
  • Cellular functionality and stress response are critical for longevity.
  • Accumulated DNA damage and cellular senescence are implicated in ageing.

Purpose of the Study:

  • To discuss the cellular and systemic mechanisms underlying ageing.
  • To explore the role of these mechanisms in age-related diseases.
  • To highlight potential therapeutic targets for extending healthy lifespan.

Main Methods:

  • Literature review and synthesis of current research on ageing mechanisms.
  • Analysis of the link between genome instability, DNA damage, and ageing.
  • Examination of non-cell-autonomous factors like cellular senescence in ageing.

Main Results:

  • Stress response pathways are linked to functional maintenance and longevity.
  • Genome instability and DNA damage accumulation contribute to ageing and age-related diseases.
  • Systemic consequences of cellular senescence play a role in regulating organismal ageing.

Conclusions:

  • Understanding cellular and systemic ageing mechanisms is crucial for addressing age-related pathologies.
  • Therapeutic strategies targeting stress response and senescence may extend healthy lifespan.
  • Interventions aimed at DNA repair and mitigating senescence hold promise for promoting longevity.