Functionally enriched epigenetic clocks reveal tissue-specific discordant aging patterns in individuals with cancer
Abstract Background Aging is a key risk factor for many diseases, including cancer, and a better understanding of its underlying molecular mechanisms may help to prevent, delay, or treat age-related pathologies. Epigenetic alterations such as DNA methylation (DNAme) changes are a hallmark of aging a...
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Nature Portfolio
2025-04-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00739-4 |
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| author | Chiara M. S. Herzog Elisa Redl James Barrett Sepideh Aminzadeh-Gohari Daniela D. Weber Julia Tevini Roland Lang Barbara Kofler Martin Widschwendter |
| author_facet | Chiara M. S. Herzog Elisa Redl James Barrett Sepideh Aminzadeh-Gohari Daniela D. Weber Julia Tevini Roland Lang Barbara Kofler Martin Widschwendter |
| author_sort | Chiara M. S. Herzog |
| collection | DOAJ |
| description | Abstract Background Aging is a key risk factor for many diseases, including cancer, and a better understanding of its underlying molecular mechanisms may help to prevent, delay, or treat age-related pathologies. Epigenetic alterations such as DNA methylation (DNAme) changes are a hallmark of aging and form the basis of so-called epigenetic clocks, yet their functional relevance and directionality in different organs during disease development is often unclear. Methods Here, we link cell-specific age-related DNAme changes with three key hallmarks of aging and cancer (senescence, promoter methylation in genes associated with stem cell fate, and dysregulated proliferation) to comprehensively dissect their association with current and future cancer development, carcinogen exposure or preventive measures, and mortality using data in different organs from over 12,510 human and 105 mouse samples, benchmarking against existing epigenetic clocks. Results Our findings offer insights into the association of functionally enriched groups of age-related DNAme changes with cancer, identify sites perturbed earliest during carcinogenesis, as well as those distinct between cancer and reprogramming that could inform strategies to prevent teratoma formation upon in vivo reprogramming. Surprisingly, both mouse and human data reveal accelerated aging in breast cancer tissue but decelerated epigenetic aging in some non-cancer surrogate samples from breast cancer patients, in particular cervical samples. Conclusions This work provides evidence for discordant systemic tissue aging in breast cancer. |
| format | Article |
| id | doaj-art-aa0c7442bae54a00adfccdec72fa7940 |
| institution | OA Journals |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-aa0c7442bae54a00adfccdec72fa79402025-08-20T02:08:09ZengNature PortfolioCommunications Medicine2730-664X2025-04-015111210.1038/s43856-025-00739-4Functionally enriched epigenetic clocks reveal tissue-specific discordant aging patterns in individuals with cancerChiara M. S. Herzog0Elisa Redl1James Barrett2Sepideh Aminzadeh-Gohari3Daniela D. Weber4Julia Tevini5Roland Lang6Barbara Kofler7Martin Widschwendter8European Translational Oncology Prevention and Screening Institute, Universität InnsbruckEuropean Translational Oncology Prevention and Screening Institute, Universität InnsbruckEuropean Translational Oncology Prevention and Screening Institute, Universität InnsbruckEuropean Translational Oncology Prevention and Screening Institute, Universität InnsbruckResearch Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical UniversityResearch Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical UniversityDepartment of Dermatology and Allergology, University Hospital of the Paracelsus Medical UniversityResearch Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, University Hospital of the Paracelsus Medical UniversityEuropean Translational Oncology Prevention and Screening Institute, Universität InnsbruckAbstract Background Aging is a key risk factor for many diseases, including cancer, and a better understanding of its underlying molecular mechanisms may help to prevent, delay, or treat age-related pathologies. Epigenetic alterations such as DNA methylation (DNAme) changes are a hallmark of aging and form the basis of so-called epigenetic clocks, yet their functional relevance and directionality in different organs during disease development is often unclear. Methods Here, we link cell-specific age-related DNAme changes with three key hallmarks of aging and cancer (senescence, promoter methylation in genes associated with stem cell fate, and dysregulated proliferation) to comprehensively dissect their association with current and future cancer development, carcinogen exposure or preventive measures, and mortality using data in different organs from over 12,510 human and 105 mouse samples, benchmarking against existing epigenetic clocks. Results Our findings offer insights into the association of functionally enriched groups of age-related DNAme changes with cancer, identify sites perturbed earliest during carcinogenesis, as well as those distinct between cancer and reprogramming that could inform strategies to prevent teratoma formation upon in vivo reprogramming. Surprisingly, both mouse and human data reveal accelerated aging in breast cancer tissue but decelerated epigenetic aging in some non-cancer surrogate samples from breast cancer patients, in particular cervical samples. Conclusions This work provides evidence for discordant systemic tissue aging in breast cancer.https://doi.org/10.1038/s43856-025-00739-4 |
| spellingShingle | Chiara M. S. Herzog Elisa Redl James Barrett Sepideh Aminzadeh-Gohari Daniela D. Weber Julia Tevini Roland Lang Barbara Kofler Martin Widschwendter Functionally enriched epigenetic clocks reveal tissue-specific discordant aging patterns in individuals with cancer Communications Medicine |
| title | Functionally enriched epigenetic clocks reveal tissue-specific discordant aging patterns in individuals with cancer |
| title_full | Functionally enriched epigenetic clocks reveal tissue-specific discordant aging patterns in individuals with cancer |
| title_fullStr | Functionally enriched epigenetic clocks reveal tissue-specific discordant aging patterns in individuals with cancer |
| title_full_unstemmed | Functionally enriched epigenetic clocks reveal tissue-specific discordant aging patterns in individuals with cancer |
| title_short | Functionally enriched epigenetic clocks reveal tissue-specific discordant aging patterns in individuals with cancer |
| title_sort | functionally enriched epigenetic clocks reveal tissue specific discordant aging patterns in individuals with cancer |
| url | https://doi.org/10.1038/s43856-025-00739-4 |
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