Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates.

Authors: Hannum G; Guinney J; Zhao L; Zhang L; Hughes G; Sadda S; Klotzle B; Bibikova M; Fan JB; Gao Y; Deconde R; Chen M; Rajapakse I; Friend S; Ideker T; Zhang K

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.

Journal: Molecular cell
Date: Nov. 28, 2012
PMID: 23177740
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Hannum G, Guinney J, Zhao L, Zhang L, Hughes G, Sadda S, Klotzle B, Bibikova M, Fan JB, Gao Y, Deconde R, Chen M, Rajapakse I, Friend S, Ideker T, Zhang K (2012) Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Molecular cell.

Lifespan Factors:
  • MDB4 methyl-CpG binding domain protein 4
  • SST Somastatin
  • KLF14 Kruppel-like factor 14
  • NEK4 NIMA (never in mitosis gene a)-related kinase 4
  • JAKMIP3 Janus kinase and microtubule interacting protein 3
  • GTPBP10 GTP-binding protein 10 (putative)
  • ELOVL2 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 2

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