Academic Journal
Exploring a targeted epigenetic clock based on mortality-associated CpGs as a potential biomarker for frailty.
| Τίτλος: | Exploring a targeted epigenetic clock based on mortality-associated CpGs as a potential biomarker for frailty. |
|---|---|
| Συγγραφείς: | Awuah J; Institute for Stem Cell Biology, RWTH Aachen University Medical School, Aachen, Germany.; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany., Dallmeier D; Institute for Geriatric Research, Ulm University Medical Center, Ulm, Germany.; Department of Research on Ageing, AGAPLESION Bethesda Clinic Ulm, Ulm, Germany.; Department of Epidemiology, Boston University School of Public Health, Boston, USA., Boehm F; Institute for Geriatric Research, Ulm University Medical Center, Ulm, Germany., Herdtle L; Institute for Geriatric Research, Ulm University Medical Center, Ulm, Germany.; Department of Research on Ageing, AGAPLESION Bethesda Clinic Ulm, Ulm, Germany., Rothenbacher D; Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany., Perez-Correa JF; Institute for Stem Cell Biology, RWTH Aachen University Medical School, Aachen, Germany. jperezecorre@ukaachen.de.; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany. jperezecorre@ukaachen.de., Wagner W; Institute for Stem Cell Biology, RWTH Aachen University Medical School, Aachen, Germany. wwagner@ukaachen.de.; Helmholtz Institute for Biomedical Engineering, RWTH Aachen University Medical School, Aachen, Germany. wwagner@ukaachen.de.; Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Aachen, Germany. wwagner@ukaachen.de. |
| Πηγή: | Clinical epigenetics [Clin Epigenetics] 2026 Jul 07; Vol. 18 (1). Date of Electronic Publication: 2026 Jul 07. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Biomed Central Country of Publication: Germany NLM ID: 101516977 Publication Model: Electronic Cited Medium: Internet ISSN: 1868-7083 (Electronic) Linking ISSN: 18687075 NLM ISO Abbreviation: Clin Epigenetics Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oct./Nov. 2011- : London : Biomed Central Original Publication: Berlin : Springer-Verlag |
| Ιατρικοί όροι (MeSH): | DNA Methylation*/genetics , CpG Islands*/genetics , Frailty*/genetics , Frailty*/mortality , Aging*/genetics, Biomarkers/analysis ; Epigenomics/methods ; Polymerase Chain Reaction/methods ; Humans ; Epigenesis, Genetic ; Female ; Male ; Aged ; Middle Aged ; Cohort Studies |
| Περίληψη: | Background: Age-related DNA methylation changes are promising biomarkers to track the individual aging process. Particularly second-generation epigenetic clocks capture aspects of biological age more accurately, but the requirement of genome wide profiles hampers implementation into practice. We therefore aimed to develop a simplified, targeted approach based on individual age- and mortality-associated CpG sites measurable by digital PCR. Results: We selected three CpG sites strongly associated with all-cause mortality in the Lothian Birth Cohorts and with chronological age in multiple publicly available repositories to establish the targeted age- and mortality-associated epigenetic clock (TaM clock). For comparison, we applied a previously published three-CpG signature selected solely for correlation with chronological age (TaC clock). These signatures were initially benchmarked using DNA methylation profiles from 20 frail and 20 non-frail participants of the ActiFE cohort. In fact, in this subset the TaM clock revealed significant association between the delta age and the frailty status based on a 32-item frailty index. Furthermore, the TaM clock outperformed the TaC clock at capturing a significant increase in epigenetic age in Down syndrome, Werner syndrome and HIV. We subsequently developed digital PCR assays to analyse 446 samples from the ActiFE cohort. One TaM clock site (cg20595453) showed significant association with both mortality and frailty. However, predictions generated by either targeted clock were not significantly associated with mortality and there was no clear relationship with frailty or age-related clinical parameters in this larger cohort. Conclusion: Our targeted signatures were not sensitive enough to reliably predict frailty or mortality in a relatively healthy study population, which seems to be a general challenge for epigenetic clocks. It may be necessary to include additional disease-associated target sites to support frailty analysis in personalized medicine. (© 2026. The Author(s).) |
| Competing Interests: | Declarations. Ethics approval and consent to participate: The Ethics Committee of Ulm University had approved the ActiFE study and this research (application no. 318/08 and 50/12) and all participants gave written consent. For the training set, we used some blood samples from the central biobank of the medical faculty of RWTH Aachen University, which was specifically approved by the Ethics Committee of RWTH Aachen Medical School (ethics approval number EK 206/09) and all participants provided written consent. Consent for publication: Not applicable. Competing interests: W. W. is a cofounder of Cygenia GmbH, which can provide services for various epigenetic signatures, including epigenetic clocks ( www.cygenia.com ). J.-F. P.-C. contributes to Cygenia, too. Apart from this, the authors have no competing interests. |
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| Contributed Indexing: | Keywords: Biological age; Biomarkers; DNA methylation; Digital PCR; Epigenetic clocks; Frailty; Second generation clocks |
| Substance Nomenclature: | 0 (Biomarkers) |
| Entry Date(s): | Date Created: 20260707 Date Completed: 20260708 Latest Revision: 20260726 |
| Update Code: | 20260726 |
| PubMed Central ID: | PMC13339440 |
| DOI: | 10.1186/s13148-026-02196-9 |
| PMID: | 42415175 |
| Βάση Δεδομένων: | MEDLINE |
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