Development of the VISAGE enhanced tool and statistical models for epigenetic age estimation in blood, buccal cells and bones

Aging (Albany NY). 2021 Mar 11;13(5):6459-6484. doi: 10.18632/aging.202783. Epub 2021 Mar 11.


DNA methylation is known as a biomarker for age with applications in forensics. Here we describe the VISAGE (VISible Attributes through GEnomics) Consortium's enhanced tool for epigenetic age estimation in somatic tissues. The tool is based on eight DNA methylation markers (44 CpGs), bisulfite multiplex PCR followed by sequencing on the MiSeq FGx platform, and three statistical prediction models for blood, buccal cells and bones. The model for blood is based on six CpGs from ELOVL2, MIR29B2CHG, KLF14, FHL2, TRIM59 and PDE4C, and predicts age with a mean absolute error (MAE) of 3.2 years, while the model for buccal cells includes five CpGs from PDE4C, MIR29B2CHG, ELOVL2, KLF14 and EDARADD and predicts age with MAE of 3.7 years, and the model for bones has six CpGs from ELOVL2, KLF14, PDE4C and ASPA and predicts age with MAE of 3.4 years. The VISAGE enhanced tool for age estimation in somatic tissues enables reliable collection of DNA methylation data from small amounts of DNA using a sensitive multiplex MPS assay that provides accurate estimation of age in blood, buccal swabs, and bones using the statistical model tailored to each tissue.

Keywords: DNA methylation; age prediction in blood and buccal cells; age prediction in bones; bisulfite amplicon MPS; epigenetic age prediction tool.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Amidohydrolases / genetics
  • Blood Chemical Analysis
  • Bone and Bones / chemistry
  • Child
  • Child, Preschool
  • CpG Islands*
  • Cyclic Nucleotide Phosphodiesterases, Type 4 / genetics
  • DNA Methylation
  • Edar-Associated Death Domain Protein / genetics
  • Epigenesis, Genetic
  • Fatty Acid Elongases / genetics
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infant
  • Kruppel-Like Transcription Factors / genetics
  • Male
  • Middle Aged
  • Models, Statistical*
  • Mouth Mucosa / chemistry
  • Multiplex Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Young Adult


  • EDARADD protein, human
  • ELOVL2 protein, human
  • Edar-Associated Death Domain Protein
  • KLF14 protein, human
  • Kruppel-Like Transcription Factors
  • Fatty Acid Elongases
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • PDE4C protein, human
  • Amidohydrolases
  • aspartoacylase