A Targeted Epigenetic Clock for the Prediction of Biological Age

Cells. 2022 Dec 14;11(24):4044. doi: 10.3390/cells11244044.

Abstract

Epigenetic clocks were initially developed to track chronological age, but accumulating evidence indicates that they can also predict biological age. They are usually based on the analysis of DNA methylation by genome-wide methods, but targeted approaches, based on the assessment of a small number of CpG sites, are advisable in several settings. In this study, we developed a targeted epigenetic clock purposely optimized for the measurement of biological age. The clock includes six genomic regions mapping in ELOVL2, NHLRC1, AIM2, EDARADD, SIRT7 and TFAP2E genes, selected from a re-analysis of existing microarray data, whose DNA methylation is measured by EpiTYPER assay. In healthy subjects (n = 278), epigenetic age calculated using the targeted clock was highly correlated with chronological age (Spearman correlation = 0.89). Most importantly, and in agreement with previous results from genome-wide clocks, epigenetic age was significantly higher and lower than expected in models of increased (persons with Down syndrome, n = 62) and decreased (centenarians, n = 106; centenarians' offspring, n = 143; nutritional intervention in elderly, n = 233) biological age, respectively. These results support the potential of our targeted epigenetic clock as a new marker of biological age and open its evaluation in large cohorts to further promote the assessment of biological age in healthcare practice.

Keywords: DNA methylation; biological age; epigenetic clock; epigenetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging* / genetics
  • Centenarians
  • CpG Islands / genetics
  • DNA Methylation / genetics
  • Down Syndrome
  • Epigenesis, Genetic*
  • Epigenomics / methods
  • Humans
  • Ubiquitin-Protein Ligases / genetics

Substances

  • NHLRC1 protein, human
  • Ubiquitin-Protein Ligases

Grants and funding

This research was funded by the European Union’s Horizon2020 research and innovation program under the Marie Skłodowska-Curie grant agreement n°675003 (“PANINI: Physical Activity and Nutrition Influences In ageing”), and under the grant agreement n°634821 (“PROPAG-AGEING”).