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Published on: July 3, 2015
Age- and oxidative stress-induced DNA damage in Drosophila intestinal stem cells as marked by Gamma-H2AX
Joung-Sun Park1, Shin-Hae Lee, Hyun-Jin Na
1Department of Molecular Biology, Pusan National University, Busan 609-735, Republic of Korea.
Abstract:
A decline in stem cell function is considered as a major cause of tissue atrophy, organ-system failure, cancer development and aging process. For a better understanding of the mechanism underlying age-related decline of stem cell function, characterization of aged stem cells is required. DNA damage induces epigenetic modifications that are associated with cell dysfunction. In mammals, γH2AX has been shown as DNA damage marker and an adaptor for recruiting chromatin modifying factors. In current study, utilizing a well-accepted Drosophila midgut model for stem-cell biology, we demonstrated aging- and oxidative stress-related accumulation of γH2AvD foci, analogous to mammal γH2AX, in Drosophila intestinal stem cells (ISCs), and obtained evidence that the changes in γH2AvD is closely associated with γ-ray-induced DNA damage in ISCs and age-related accumulation of 8-oxo-2'-deoxyguanosine. The significance of our study is to document the first direct evidence for the accumulation of age-related DNA-damage in ISCs, and to show γH2AvD as a useful biomarker in exploring the molecular mechanisms underlying stem cell aging in the Drosophila midgut.
Insights
Stem cell aging leads to tissue dysfunction. This study shows that DNA damage accumulates in aged Drosophila intestinal stem cells (ISCs), with γH2AvD serving as a key biomarker for stem cell aging.
Area of Science:
- Stem cell biology
- Aging research
- Molecular mechanisms of aging
Background:
- Stem cell functional decline contributes to aging and disease.
- DNA damage and epigenetic changes are linked to cell dysfunction.
- γH2AX is a known DNA damage marker in mammals.
Purpose of the Study:
- To investigate the mechanisms of age-related stem cell dysfunction.
- To characterize aged stem cells in a model organism.
- To identify biomarkers for stem cell aging.
Main Methods:
- Utilized the Drosophila midgut model for stem cell studies.
- Assessed the accumulation of γH2AvD foci in intestinal stem cells (ISCs).
- Correlated γH2AvD changes with DNA damage markers like 8-oxo-2'-deoxyguanosine.
Main Results:
- Demonstrated aging- and oxidative stress-related accumulation of γH2AvD in Drosophila ISCs.
- Showed γH2AvD accumulation is associated with γ-ray-induced DNA damage.
- Observed age-related accumulation of 8-oxo-2'-deoxyguanosine in ISCs.
Conclusions:
- Provided the first direct evidence of age-related DNA damage accumulation in ISCs.
- Established γH2AvD as a valuable biomarker for studying stem cell aging.
- The Drosophila midgut is a suitable model for exploring stem cell aging mechanisms.
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