Wang Shuo, Prizment Anna, Moshele Puleng, Vivek Sithara, Guan Weihua, Blaes Anne H, Nelson Heather H, Thyagarajan Bharat
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Nat Commun. 2025 Jul 1;16(1):5916. doi: 10.1038/s41467-025-60913-z.
Cancer survivors may have higher biological age (BA) than cancer-free persons (controls). In HRS, we examined the associations of BA with cancer prevalence and mortality. BA was estimated by the Klemera and Doubal method (KDM-BA), phenotypic age (PhenoAge), and subjective age (SA) among 946 cancer survivors and 4555 controls; and by epigenetic clocks (Horvath, Hannum, Levine, GrimAge, Zhang Score (ZS), and methylation-based pace of aging (mPOA)) among 582 cancer survivors and 2805 controls. Age acceleration is estimated as residuals regressed on chronological age. There are significant multivariable associations with cancer prevalence for Hannum, GrimAge, and SA, and ZS (logistic regression), and with mortality for PhenoAge, Hannum, Levine, GrimAge, and ZS in cancer survivors, and for KDM-BA, PhenoAge, and ZS in controls (Cox regression). The strongest association in cancer survivors is for GrimAge (HR per 1 SD = 1.80, p < 0.001). PhenoAge and first- and second-generation epigenetic clocks hold promise for predicting mortality in cancer survivors.
癌症幸存者的生物学年龄（BA）可能高于无癌症者（对照组）。在健康与退休研究（HRS）中，我们研究了BA与癌症患病率和死亡率之间的关联。在946名癌症幸存者和4555名对照组中，通过克莱梅拉和杜巴尔方法（KDM-BA）、表型年龄（PhenoAge）和主观年龄（SA）来估计BA；在582名癌症幸存者和2805名对照组中，通过表观遗传时钟（霍瓦斯、汉纳姆、莱文、GrimAge、张评分（ZS）和基于甲基化的衰老速度（mPOA））来估计BA。年龄加速被估计为按实足年龄回归的残差。在癌症幸存者中，汉纳姆、GrimAge、SA和ZS与癌症患病率存在显著的多变量关联（逻辑回归），PhenoAge、汉纳姆、莱文、GrimAge和ZS与死亡率存在显著的多变量关联；在对照组中，KDM-BA、PhenoAge和ZS与死亡率存在显著的多变量关联（Cox回归）。在癌症幸存者中，与死亡率关联最强的是GrimAge（每1个标准差的风险比=1.80，p<0.001）。PhenoAge以及第一代和第二代表观遗传时钟有望预测癌症幸存者的死亡率。
