alexa Accumulation of DNA damage-induced chromatin alterations in tissue-specific stem cells: the driving force of aging?
Medicine

Medicine

Journal of Gerontology & Geriatric Research

Author(s): Schuler N, Rbe CE

Abstract Share this page

Abstract Accumulation of DNA damage leading to stem cell exhaustion has been proposed to be a principal mechanism of aging. Using 53BP1-foci as a marker for DNA double-strand breaks (DSBs), hair follicle stem cells (HFSCs) in mouse epidermis were analyzed for age-related DNA damage response (DDR). We observed increasing amounts of 53BP1-foci during the natural aging process independent of telomere shortening and after protracted low-dose radiation, suggesting substantial accumulation of DSBs in HFSCs. Electron microscopy combined with immunogold-labeling showed multiple small 53BP1 clusters diffusely distributed throughout the highly compacted heterochromatin of aged HFSCs, but single large 53BP1 clusters in irradiated HFSCs. These remaining 53BP1 clusters did not colocalize with core components of non-homologous end-joining, but with heterochromatic histone modifications. Based on these results we hypothesize that these lesions were not persistently unrepaired DSBs, but may reflect chromatin rearrangements caused by the repair or misrepair of DSBs. Flow cytometry showed increased activation of repair proteins and damage-induced chromatin modifications, triggering apoptosis and cellular senescence in irradiated, but not in aged HFSCs. These results suggest that accumulation of DNA damage-induced chromatin alterations, whose structural dimensions reflect the complexity of the initial genotoxic insult, may lead to different DDR events, ultimately determining the biological outcome of HFSCs. Collectively, our findings support the hypothesis that aging might be largely the remit of structural changes to chromatin potentially leading to epigenetically induced transcriptional deregulation.
This article was published in PLoS One and referenced in Journal of Gerontology & Geriatric Research

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

agriaquaculture@omicsonline.com

1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

biochemjournals@omicsonline.com

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

business@omicsonline.com

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

chemistryjournals@omicsonline.com

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

clinicaljournals@omicsonline.com

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

engineeringjournals@omicsonline.com

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

nutritionjournals@omicsonline.com

1-702-714-7001Extn: 9042

General Science

Andrea Jason

generalscience@omicsonline.com

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

geneticsmolbio@omicsonline.com

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

immunomicrobiol@omicsonline.com

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

materialsci@omicsonline.com

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

nursinghealthcare@omicsonline.com

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

medicaljournals@omicsonline.com

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

neuropsychology@omicsonline.com

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

pharmajournals@omicsonline.com

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

social_politicalsci@omicsonline.com

1-702-714-7001Extn: 9042

 
© 2008- 2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords