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探讨脂质心血管队列中相对端粒长度与表观遗传时钟的关系。

Exploring the Relationship of Relative Telomere Length and the Epigenetic Clock in the LipidCardio Cohort.

机构信息

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and the Berlin Institute of Health, Lipid Clinic at the Interdisciplinary Metabolism Center, 13353 Berlin, Germany.

Medizinische Klinik mit Schwerpunkt Nephrologie und Intensivmedizin, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.

出版信息

Int J Mol Sci. 2019 Jun 21;20(12):3032. doi: 10.3390/ijms20123032.

Abstract

Telomere length has been accepted widely as a biomarker of aging. Recently, a novel candidate biomarker has been suggested to predict an individual's chronological age with high accuracy: The epigenetic clock is based on the weighted DNA methylation (DNAm) fraction of a number of cytosine-phosphate-guanine sites (CpGs) selected by penalized regression analysis. Here, an established methylation-sensitive single nucleotide primer extension method was adapted, to estimate the epigenetic age of the 1005 participants of the LipidCardio Study, a patient cohort characterised by high prevalence of cardiovascular disease, based on a seven CpGs epigenetic clock. Furthermore, we measured relative leukocyte telomere length (rLTL) to assess the relationship between the established and the promising new measure of biological age. Both rLTL (0.79 ± 0.14) and DNAm age (69.67 ± 7.27 years) were available for 773 subjects (31.6% female; mean chronological age= 69.68 ± 11.01 years; mean DNAm age acceleration = -0.01 ± 7.83 years). While we detected a significant correlation between chronological age and DNAm age ( = 779, = 0.69), we found neither evidence of an association between rLTL and the DNAm age ( = 3.00, = 0.18) nor rLTL and the DNAm age acceleration ( = 2.76, = 0.22) in the studied cohort, suggesting that DNAm age and rLTL measure different aspects of biological age.

摘要

端粒长度已被广泛接受为衰老的生物标志物。最近,一种新的候选生物标志物被提出,可以高精度地预测个体的实际年龄:表观遗传时钟是基于通过惩罚回归分析选择的多个胞嘧啶-磷酸-鸟嘌呤位点(CpG)的加权 DNA 甲基化(DNAm)分数。在这里,我们适应了一种已建立的甲基化敏感的单核苷酸引物延伸方法,以根据七个 CpG 表观遗传时钟,估计 LipidCardio 研究的 1005 名参与者的表观遗传年龄,该研究是一个患者队列,具有心血管疾病的高患病率。此外,我们测量了相对白细胞端粒长度(rLTL),以评估已建立的和有前途的新生物年龄测量方法之间的关系。rLTL(0.79 ± 0.14)和 DNAm 年龄(69.67 ± 7.27 岁)均可用于 773 名受试者(31.6%为女性;平均实际年龄= 69.68 ± 11.01 岁;平均 DNAm 年龄加速= -0.01 ± 7.83 岁)。虽然我们检测到实际年龄和 DNAm 年龄之间存在显著相关性( = 779, = 0.69),但我们在研究队列中既没有发现 rLTL 与 DNAm 年龄之间存在关联的证据( = 3.00, = 0.18),也没有发现 rLTL 与 DNAm 年龄加速之间存在关联的证据( = 2.76, = 0.22),这表明 DNAm 年龄和 rLTL 测量生物年龄的不同方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8fde/6628615/d816ff25d5ec/ijms-20-03032-g0A1.jpg

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