Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease
Open accessAbstract
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.
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Mice with short telomeres show altered secretory profiles in their serum.
“Differential secretory profiles have also been detected in sera from mice with short telomeres121.”
From The telomere syndromes (2012) · cites this paper as [121]
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- Authors
- Jiang, H., Schiffer, E., Song, Z., Wang, J., Zürbig, P., Thedieck, K., Moes, S., Bantel, H., Saal, N., Jantos, J., Brecht, M., Jenö, P., Hall, M. N., Hager, K., Manns, M. P., Hecker, H., Ganser, A., Döhner, K., Bartke, A., Meissner, C., Mischak, H., Ju, Z., & Rudolph, K. L.
- Affiliations
- Max Planck Society (DE)
- Mosaiques Diagnostics and Therapeutics (Germany) (DE)
- University of Basel (CH)
- Universität Ulm (DE)
- Mosaiques Diagnostics and Therapeutics AG, Mellendorfer Strasse 7-9, 30625 Hannover, Germany;
- Department of Geriatric Medicine, Henriettenstiftung, D-30171 Hannover, Germany;
- Biostatistics, and
- Medizinische Hochschule Hannover (DE)
- SIU Medicine (US)
- University Hospital Schleswig-Holstein (DE)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-08-12
- Volume
- 105
- Issue
- 32
- Pages
- 11299-11304
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2516278
- OpenAlex
- W2169753550
- Cited by
- 169
- References
- 42
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 4 · 2018: 7 · 2017: 7 · 2016: 5 · 2015: 11 · 2014: 12 · 2013: 11 · 2012: 18
- FWCI
- 12.19
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-04-02)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- edoc (University of Basel) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- European Commission (LSHC-CT-2005-018704)
- Deutsche Forschungsgemeinschaft (SFB-738)
- Deutsche Krebshilfe
- Institut National Du Cancer
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Keywords
- telomere dysfunction, DNA damage response, aging biomarkers, telomere shortening, cellular senescence, apoptosis, cramps, stathmin, EF-1α, chitinase, myelodysplastic syndrome, liver cirrhosis, plasma biomarkers, age-related diseases, cell turnover
- MeSH terms
- Aging, Animals, Bone Marrow Cells, Chitinases, DNA Damage, Female, Fibroblasts, Fibrosis, Gamma Rays, Humans, Male, Myelodysplastic Syndromes, Biomarkers, Up-Regulation, Telomere, Cellular Senescence, Apoptosis, Mice, Knockout, Telomerase, Peptide Elongation Factor 1, Antimicrobial Cationic Peptides, Stathmin, Mice, Cathelicidins
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