Drew R Nannini, Rene Cortese, Christopher VonTungeln, Gerhard C Hildebrandt
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Six markers of biological age acceleration were estimated from DNA methylation levels. Multiple linear regression analyses were performed to evaluate the association between each metric of biological age acceleration and chemotherapy. After adjusting for chronological age and race, intrinsic epigenetic age acceleration (<i>p</i> = 0.041), extrinsic epigenetic age acceleration (<i>p</i> = 0.050), PhenoAge acceleration (<i>p</i> = 0.001), GrimAge acceleration (<i>p</i> < 0.001), and DunedinPACE (<i>p</i> = 0.006) were significantly higher and telomere length (<i>p</i> = 0.027) was significantly lower following the first cycle of chemotherapy compared to before treatment initiation. These results demonstrate greater biological ageing as estimated from DNA methylation following chemotherapy in women with breast cancer. Our findings illustrate that cytotoxic therapies may modulate the ageing process among breast cancer patients and may also have implications for age-related health conditions in cancer survivors.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"19 1","pages":"2360160"},"PeriodicalIF":2.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146438/pdf/","citationCount":"0","resultStr":"{\"title\":\"Chemotherapy-induced acceleration of DNA methylation-based biological age in breast cancer.\",\"authors\":\"Drew R Nannini, Rene Cortese, Christopher VonTungeln, Gerhard C Hildebrandt\",\"doi\":\"10.1080/15592294.2024.2360160\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Breast cancer is the most common cancer diagnosed in women and is often treated with chemotherapy. Although previous studies have demonstrated increasing biological age in patients who receive chemotherapy, evaluation of this association with DNA methylation-based markers of biological ageing may provide novel insight into the role of chemotherapy on the ageing process. We therefore sought to investigate the association between chemotherapy and markers of biological ageing as estimated from DNA methylation in women with breast cancer. DNA methylation profiling was performed on peripheral blood collected from 18 patients before and after the first cycle of chemotherapy using the Infinium HumanMethylation450 BeadChip. Six markers of biological age acceleration were estimated from DNA methylation levels. Multiple linear regression analyses were performed to evaluate the association between each metric of biological age acceleration and chemotherapy. 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Our findings illustrate that cytotoxic therapies may modulate the ageing process among breast cancer patients and may also have implications for age-related health conditions in cancer survivors.</p>\",\"PeriodicalId\":11767,\"journal\":{\"name\":\"Epigenetics\",\"volume\":\"19 1\",\"pages\":\"2360160\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11146438/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Epigenetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/15592294.2024.2360160\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/31 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epigenetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/15592294.2024.2360160","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/31 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
乳腺癌是女性最常见的癌症,通常采用化疗治疗。尽管之前的研究已经证明接受化疗的患者的生物年龄在增加,但评估这种与基于 DNA 甲基化的生物老化标志物之间的关联可能会为了解化疗在老化过程中的作用提供新的视角。因此,我们试图研究化疗与根据 DNA 甲基化估计的乳腺癌女性患者生物衰老标志物之间的关联。我们使用 Infinium HumanMethylation450 BeadChip 对第一周期化疗前后收集的 18 名患者的外周血进行了 DNA 甲基化分析。根据 DNA 甲基化水平估算出生物年龄加速度的六个标志物。进行了多元线性回归分析,以评估生物年龄加速的各项指标与化疗之间的关联。在对年代年龄和种族进行调整后,与开始治疗前相比,化疗第一周期后的内在表观遗传年龄加速度(p = 0.041)、外在表观遗传年龄加速度(p = 0.050)、PhenoAge 加速度(p = 0.001)、GrimAge 加速度(p = 0.006)显著升高,端粒长度(p = 0.027)显著降低。这些结果表明,根据 DNA 甲基化估计,乳腺癌妇女化疗后的生物老化程度更高。我们的研究结果表明,细胞毒性疗法可能会调节乳腺癌患者的衰老过程,也可能对癌症幸存者与年龄相关的健康状况产生影响。
Chemotherapy-induced acceleration of DNA methylation-based biological age in breast cancer.
Breast cancer is the most common cancer diagnosed in women and is often treated with chemotherapy. Although previous studies have demonstrated increasing biological age in patients who receive chemotherapy, evaluation of this association with DNA methylation-based markers of biological ageing may provide novel insight into the role of chemotherapy on the ageing process. We therefore sought to investigate the association between chemotherapy and markers of biological ageing as estimated from DNA methylation in women with breast cancer. DNA methylation profiling was performed on peripheral blood collected from 18 patients before and after the first cycle of chemotherapy using the Infinium HumanMethylation450 BeadChip. Six markers of biological age acceleration were estimated from DNA methylation levels. Multiple linear regression analyses were performed to evaluate the association between each metric of biological age acceleration and chemotherapy. After adjusting for chronological age and race, intrinsic epigenetic age acceleration (p = 0.041), extrinsic epigenetic age acceleration (p = 0.050), PhenoAge acceleration (p = 0.001), GrimAge acceleration (p < 0.001), and DunedinPACE (p = 0.006) were significantly higher and telomere length (p = 0.027) was significantly lower following the first cycle of chemotherapy compared to before treatment initiation. These results demonstrate greater biological ageing as estimated from DNA methylation following chemotherapy in women with breast cancer. Our findings illustrate that cytotoxic therapies may modulate the ageing process among breast cancer patients and may also have implications for age-related health conditions in cancer survivors.
期刊介绍:
Epigenetics publishes peer-reviewed original research and review articles that provide an unprecedented forum where epigenetic mechanisms and their role in diverse biological processes can be revealed, shared, and discussed.
Epigenetics research studies heritable changes in gene expression caused by mechanisms others than the modification of the DNA sequence. Epigenetics therefore plays critical roles in a variety of biological systems, diseases, and disciplines. Topics of interest include (but are not limited to):
DNA methylation
Nucleosome positioning and modification
Gene silencing
Imprinting
Nuclear reprogramming
Chromatin remodeling
Non-coding RNA
Non-histone chromosomal elements
Dosage compensation
Nuclear organization
Epigenetic therapy and diagnostics
Nutrition and environmental epigenetics
Cancer epigenetics
Neuroepigenetics