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Updated: Jul 17, 2026

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
Published on: June 8, 2018
A third link connecting aging with double strand break repair
William R Engels1, Dena Johnson-Schlitz, Carlos Flores
1Genetics Department, University of Wisconsin, Madison, Wisconsin 53706, USA. wrengels@wisc.edu
Abstract:
Until recently, the connection between aging and DNA repair has rested on two classes of observation. First, DNA damage and unrepaired double-strand breaks (DSBs) accumulate with age. Second, several defects in DNA repair genes are associated with early onset of age-related diseases and other signs of premature aging. Now, a third link has emerged: The mechanisms by which cells repair DSB damage can change dramatically with age, shifting from simpler end-joining processes in younger organisms to homologous mechanisms in which missing genetic information is restored through use of a template. So far this third link between aging and DNA repair has only been observed in a small number of experimental systems, and cannot yet claim the generality of the other two. Here we review the evidence for this phenomenon and present new data testing models for the underlying causes. If the generality of age-related changes in DSB repair pathway usage can be established, it will provide a new insight into the underlying molecular basis of aging and how evolution has shaped these processes.
Insights
Aging DNA repair mechanisms shift from simple end-joining to homologous repair as organisms age. This age-related change in double-strand break (DSB) repair pathway usage offers new insights into aging molecular basis.
Area of Science:
- Genetics
- Molecular Biology
- Gerontology
Background:
- Accumulation of DNA damage, particularly double-strand breaks (DSBs), is a hallmark of aging.
- Defects in DNA repair genes are linked to premature aging and age-related diseases.
Purpose of the Study:
- To investigate the emerging third link between aging and DNA repair: age-dependent changes in DSB repair mechanisms.
- To review existing evidence and present new data on the underlying causes of these shifts.
Main Methods:
- Review of existing literature on aging and DNA repair.
- Presentation of new experimental data analyzing DSB repair pathway usage in different age groups.
- Testing models for the causes of age-related shifts in repair mechanisms.
Main Results:
- A shift in DNA double-strand break (DSB) repair mechanisms with age has been observed.
- Younger organisms predominantly use simpler end-joining repair, while older organisms show a trend towards homologous repair pathways.
- This phenomenon has been observed in a limited number of experimental systems.
Conclusions:
- Age-related changes in DNA double-strand break (DSB) repair pathway usage represent a significant, though not yet universally established, link between aging and DNA repair.
- Establishing the generality of this phenomenon could provide novel insights into the molecular underpinnings of aging.
- Understanding these shifts may illuminate how evolutionary processes have shaped aging and repair mechanisms.
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