title: Genome-wide methylation profiles reveal quantitative views of human aging rates.
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.
authors.affiliation: Department of Bioengineering, University of California, San Diego, CA 92093, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Hannum
authors.affiliation: Sage Bionetworks, Seattle, WA 98109, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Guinney
authors.affiliation: Molecular Medicine Research Center and Department of Ophthalmology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.|Institute for Genomic Medicine, University of California, San Diego, CA 92093, USA.|Department of Ophthalmology, University of California, San Diego, CA 92093, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Molecular Medicine Research Center and Department of Ophthalmology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.|Institute for Genomic Medicine, University of California, San Diego, CA 92093, USA.|Department of Ophthalmology, University of California, San Diego, CA 92093, USA.|Guangzhou iGenomics Co., Ltd, Guangzhou 510300, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute for Genomic Medicine, University of California, San Diego, CA 92093, USA.|Department of Ophthalmology, University of California, San Diego, CA 92093, USA.
authors.forename: Guy
authors.initials: G
authors.lastname: Hughes
authors.affiliation: Doheny Eye Institute, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: SriniVas
authors.initials: S
authors.lastname: Sadda
authors.affiliation: Illumina Incorporation, San Diego, CA 92122, USA.
authors.forename: Brandy
authors.initials: B
authors.lastname: Klotzle
authors.affiliation: Illumina Incorporation, San Diego, CA 92122, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Bibikova
authors.affiliation: Illumina Incorporation, San Diego, CA 92122, USA.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: Lieber Institute, Johns Hopkins University, Baltimore, MD 21205, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Bioengineering, University of California, San Diego, CA 92093, USA.|Department of Medicine, University of California, San Diego, CA 92093, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Deconde
authors.affiliation: Department of Bioengineering, University of California, San Diego, CA 92093, USA.
authors.forename: Menzies
authors.initials: M
authors.lastname: Chen
authors.affiliation: Division of Basic Sciences and Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, WA 98110, USA.
authors.forename: Indika
authors.initials: I
authors.lastname: Rajapakse
authors.affiliation: Sage Bionetworks, Seattle, WA 98109, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Friend
authors.affiliation: Department of Bioengineering, University of California, San Diego, CA 92093, USA.|Institute for Genomic Medicine, University of California, San Diego, CA 92093, USA.|Department of Medicine, University of California, San Diego, CA 92093, USA.
authors.forename: Trey
authors.initials: T
authors.lastname: Ideker
authors.affiliation: Molecular Medicine Research Center and Department of Ophthalmology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.|Institute for Genomic Medicine, University of California, San Diego, CA 92093, USA.|Department of Ophthalmology, University of California, San Diego, CA 92093, USA.
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010641:Phenotype; D017422:Sequence Analysis, DNA; D059467:Transcriptome; D055815:Young Adult