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Mol Cell. 2013 Jan 24;49(2):359-367. doi: 10.1016/j.molcel.2012.10.016. Epub 2012 Nov 21.

Genome-wide methylation profiles reveal quantitative views of human aging rates.

Author information

1
Department of Bioengineering, University of California, San Diego, CA 92093, USA.
2
Sage Bionetworks, Seattle, WA 98109, USA.
3
Molecular Medicine Research Center and Department of Ophthalmology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
4
Institute for Genomic Medicine, University of California, San Diego, CA 92093, USA.
5
Department of Ophthalmology, University of California, San Diego, CA 92093, USA.
6
Guangzhou iGenomics Co., Ltd, Guangzhou 510300, China.
7
Doheny Eye Institute, University of Southern California, Los Angeles, CA 90033, USA.
8
Illumina Incorporation, San Diego, CA 92122, USA.
9
Lieber Institute, Johns Hopkins University, Baltimore, MD 21205, USA.
10
Department of Medicine, University of California, San Diego, CA 92093, USA.
11
Division of Basic Sciences and Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA 98110, USA.
#
Contributed equally

Abstract

The ability to measure human aging from molecular profiles has practical implications in many fields, including disease prevention and treatment, forensics, and extension of life. Although chronological age has been linked to changes in DNA methylation, the methylome has not yet been used to measure and compare human aging rates. Here, we build a quantitative model of aging using measurements at more than 450,000 CpG markers from the whole blood of 656 human individuals, aged 19 to 101. This model measures the rate at which an individual's methylome ages, which we show is impacted by gender and genetic variants. We also show that differences in aging rates help explain epigenetic drift and are reflected in the transcriptome. Moreover, we show how our aging model is upheld in other human tissues and reveals an advanced aging rate in tumor tissue. Our model highlights specific components of the aging process and provides a quantitative readout for studying the role of methylation in age-related disease.

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PMID:
23177740
PMCID:
PMC3780611
DOI:
10.1016/j.molcel.2012.10.016
[Indexed for MEDLINE]
Free PMC Article

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