Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease

Jiang, H. and Schiffer, E. and Song, Z. and Wang, J. and Zurbig, P. and Thedieck, K. and Moes, S. and Bantel, H. and Saal, N. and Jantos, J. and Brecht, M. and Jeno, P. and Hall, M. N. and Hager, K. and Manns, M. P. and Hecker, H. and Ganser, A. and Dohner, K. and Bartke, A. and Meissner, C. and Mischak, H. and Ju, Z. and Rudolph, K. L.. (2008) Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease. Proceedings of the National Academy of Sciences of the United States of America, 105 (32). pp. 11299-11304.

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Official URL: http://edoc.unibas.ch/dok/A5258133

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Telomere dysfunction limits the proliferative capacity of human cells by activation of DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in the vast majority of tissues during aging, and telomere shortening is accelerated in chronic diseases that increase the rate of cell turnover. Yet, the functional role of telomere dysfunction and DNA damage in human aging and diseases remains under debate. Here, we identified marker proteins (i.e., CRAMP, stathmin, EF-1alpha, and chitinase) that are secreted from telomere-dysfunctional bone-marrow cells of late generation telomerase knockout mice (G4mTerc(-/-)). The expression levels of these proteins increase in blood and in various tissues of aging G4mTerc(-/-) mice but not in aging mice with long telomere reserves. Orthologs of these proteins are up-regulated in late-passage presenescent human fibroblasts and in early passage human cells in response to gamma-irradiation. The study shows that the expression level of these marker proteins increases in the blood plasma of aging humans and shows a further increase in geriatric patients with aging-associated diseases. Moreover, there was a significant increase in the expression of the biomarkers in the blood plasma of patients with chronic diseases that are associated with increased rates of cell turnover and telomere shortening, such as cirrhosis and myelodysplastic syndromes (MDS). Analysis of blinded test samples validated the effectiveness of the biomarkers to discriminate between young and old, and between disease groups (MDS, cirrhosis) and healthy controls. These results support the concept that telomere dysfunction and DNA damage are interconnected pathways that are activated during human aging and disease.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:11 Mar 2019 16:29
Deposited On:22 Mar 2012 13:19

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