Cell-free DNA as a biomarker of aging
Cell-free DNA as a biomarker of aging
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DOI：
10.1111/acel.12890
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发表时间：
2019-02-01
期刊：
影响因子：
7.8
通讯作者：
Neretti, Nicola
中科院分区：
文献类型：
--
作者：
Teo, Yee Voan;Capri, Miriam;Neretti, Nicola
无细胞DNA（cfDNA）存在于循环血浆和其他体液中，并且已知主要来源于凋亡细胞。在这里，我们通过分析来自不同年龄组个体血液的cfDNA，提供了人类衰老中全局和局部染色质变化的第一个体内证据。我们的结果表明，从cfDNA推断的核小体信号与在其他模型系统中的细胞衰老和老化中观察到的异染色质的重新分布一致。此外，我们检测到在几个基因组位置，如转录起始和终止位点，L1HS逆转录转座子的5UTR和二聚体的CfY元件随着年龄的相对cfDNA损失。我们的研究结果还显示，年龄和健康状况恶化与不同组织中细胞信号的增加有关。总之，我们的结果表明，来自人血浆的循环cfDNA的测序可以用作研究体内表观基因组的年龄相关变化的非侵入性方法。
Cell-free DNA (cfDNA) is present in the circulating plasma and other body fluids and is known to originate mainly from apoptotic cells. Here, we provide the first in vivo evidence of global and local chromatin changes in human aging by analyzing cfDNA from the blood of individuals of different age groups. Our results show that nucleosome signals inferred from cfDNA are consistent with the redistribution of heterochromatin observed in cellular senescence and aging in other model systems. In addition, we detected a relative cfDNA loss at several genomic locations, such as transcription start and termination sites, 5UTR of L1HS retrotransposons and dimeric AluY elements with age. Our results also revealed age and deteriorating health status correlate with increased enrichment of signals from cells in different tissues. In conclusion, our results show that the sequencing of circulating cfDNA from human blood plasma can be used as a noninvasive methodology to study age-associated changes to the epigenome in vivo.