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Aging Cell. 2019 Feb;18(1):e12890. doi: 10.1111/acel.12890. Epub 2018 Dec 20.

Cell-free DNA as a biomarker of aging.

Author information

1
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island.
2
CIG Interdepartmental Centre "Galvani", University of Bologna, Bologna, Italy.
3
DIMES-Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
4
Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology & Metabolism, Department of Medicine, Imperial College London, London, UK.
5
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
6
IRCCS, Institute of Neurological Sciences of Bologna, Bologna, Italy.
7
Center for Computational Molecular Biology, Brown University, Providence, Rhode Island.

Abstract

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, 5'UTR 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.

KEYWORDS:

aging; cell-free DNA; epigenetics

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