Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan, USA.
Translational Research Center, College of Dentistry, New York University, New York, New York, USA.
Aging Cell. 2024 Jul;23(7):e14174. doi: 10.1111/acel.14174. Epub 2024 Apr 17.
Telomere length (TL) is an important indicator of cellular aging. Shorter TL is associated with several age-related diseases including coronary heart disease, heart failure, diabetes, osteoporosis, and cancer. Recently, a DNA methylation-based TL (DNAmTL) estimator has been developed as an alternative method for directly measuring TL. In this study, we examined the association of DNAmTL with cancer prevalence and mortality risk among people with and without HIV in the Veterans Aging Cohort Study Biomarker Cohort (VACS, N = 1917) and Women's Interagency HIV Study Cohort (WIHS, N = 481). We profiled DNAm in whole blood (VACS) or in peripheral blood mononuclear cells (WIHS) using an array-based method. Cancer prevalence was estimated from electronic medical records and cancer registry data. The VACS Index was used as a measure of physiologic frailty. Models were adjusted for self-reported race and ethnicity, batch, smoking status, alcohol consumption, and five cell types (CD4, CD8, NK, B cell, and monocyte). We found that people with HIV had shorter average DNAmTL than those without HIV infection [beta = -0.25, 95% confidence interval (-0.32, -0.18), p = 1.48E-12]. Greater value of VACS Index [beta = -0.002 (-0.003, -0.001), p = 2.82E-05] and higher cancer prevalence [beta = -0.07 (-0.10, -0.03), p = 1.37E-04 without adjusting age] were associated with shortened DNAmTL. In addition, one kilobase decrease in DNAmTL was associated with a 40% increase in mortality risk [hazard ratio: 0.60 (0.44, 0.82), p = 1.42E-03]. In summary, HIV infection, physiologic frailty, and cancer are associated with shortening DNAmTL, contributing to an increased risk of all-cause mortality.
端粒长度 (TL) 是细胞衰老的一个重要指标。TL 较短与几种与年龄相关的疾病有关，包括冠心病、心力衰竭、糖尿病、骨质疏松症和癌症。最近，一种基于 DNA 甲基化的 TL（DNAmTL）估计器已被开发出来，作为直接测量 TL 的替代方法。在这项研究中，我们在退伍军人衰老队列研究生物标志物队列（VACS，N=1917）和妇女机构间艾滋病毒研究队列（WIHS，N=481）中检查了 DNAmTL 与艾滋病毒感染者和非感染者癌症患病率和死亡风险之间的关联。我们使用基于阵列的方法对全血（VACS）或外周血单核细胞（WIHS）中的 DNAm 进行了分析。从电子病历和癌症登记数据中估计癌症患病率。VACS 指数被用作生理脆弱性的衡量标准。模型调整了自我报告的种族和民族、批次、吸烟状况、饮酒和五种细胞类型（CD4、CD8、NK、B 细胞和单核细胞）。我们发现，艾滋病毒感染者的平均 DNAmTL 短于未感染艾滋病毒的人[β=-0.25，95%置信区间（-0.32，-0.18），p=1.48E-12]。VACS 指数较高[β=-0.002（-0.003，-0.001），p=2.82E-05]和癌症患病率较高[β=-0.07（-0.10，-0.03），p=1.37E-04，未经年龄调整]与 DNAmTL 缩短有关。此外，DNAmTL 每减少 1 千碱基，死亡风险增加 40%[风险比：0.60（0.44，0.82），p=1.42E-03]。总之，艾滋病毒感染、生理脆弱性和癌症与 DNAmTL 缩短有关，导致全因死亡率增加。
