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Updated: Jul 10, 2026
08:31
Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
Published on: June 8, 2018
Delayed kinetics of DNA double-strand break processing in normal and pathological aging
Olga A Sedelnikova1, Izumi Horikawa, Christophe Redon
1Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. sedelnio@mail.nih.gov
Aging Cell
|November 17, 2007
Summary
Aging impairs the cell
Area of Science:
- Cellular and Molecular Biology
- Genetics
- Gerontology
Background:
- Accumulation of DNA damage is linked to cellular senescence and organismal aging.
- The molecular mechanisms behind age-related decline in DNA damage sensing and repair remain unclear.
- DNA damage response (DDR) efficiency may decrease with age, impacting genomic stability.
Purpose of the Study:
- To investigate age-dependent quantitative and qualitative changes in the DNA damage response in human cells.
- To examine the role of DNA double-strand breaks (DSBs) and phosphorylated histone H2AX (gamma-H2AX) foci in aging.
- To compare DNA damage response in normal aging versus premature aging (Werner syndrome).
Main Methods:
- Analysis of endogenous gamma-H2AX foci in human fibroblasts and lymphocytes from young and old donors.
- Comparison of gamma-H2AX foci in normal fibroblasts versus fibroblasts from Werner syndrome patients.
- Assessment of DNA double-strand break (DSB) repair protein recruitment to gamma-H2AX foci in relation to age.
Main Results:
- The incidence of endogenous gamma-H2AX foci increases with age.
- Fibroblasts from Werner syndrome patients show a higher incidence of gamma-H2AX foci compared to age-matched normal donors.
- Recruitment rates of DSB repair proteins to gamma-H2AX foci decrease with age, potentially due to slower foci growth.
Conclusions:
- Decreased efficiency in processing DNA double-strand breaks (DSBs) and recruiting repair proteins contributes to genome instability in normal and pathological aging.
- Age-related decline in DNA repair mechanisms, indicated by gamma-H2AX foci dynamics, is a significant factor in aging.
- Understanding these age-dependent changes in DNA damage response is crucial for addressing age-related genomic instability.
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