A Cost-Effective Saliva-Based Human Epigenetic Clock Using 10 CpG Sites Identified with the Illumina EPIC 850k Array
<b>Background/Objectives:</b> DNA methylation profiles have emerged as robust biomarkers of ageing, leading to the development of “epigenetic clocks” that estimate biological age. Most established clocks (e.g., Horvath’s 353-CpG pan-tissue clock and Hannum’s 71-CpG blood clock) require d...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | DNA |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2673-8856/5/2/28 |
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| Summary: | <b>Background/Objectives:</b> DNA methylation profiles have emerged as robust biomarkers of ageing, leading to the development of “epigenetic clocks” that estimate biological age. Most established clocks (e.g., Horvath’s 353-CpG pan-tissue clock and Hannum’s 71-CpG blood clock) require dozens to hundreds of CpG sites. This study presents a novel saliva-specific epigenetic clock built on 10 sites identified from Illumina MethylationEPIC (850 k) array data. <b>Methods</b>: Saliva DNA methylation was analysed from 3408 individuals (age range 15–89 years, 68% male, 32% female, no diagnosed disease) from the Muhdo Health Ltd. dataset (2022–2024), and 10 CpG sites were selected where methylation levels showed the strongest positive correlations with chronological age (Pearson r = 0.48–0.66, <i>p</i> < 1 × 10−20). These CpGs map to genes involved in developmental and metabolic pathways (including <i>ELOVL2</i>, <i>CHGA</i>, <i>OTUD7A</i>, <i>PRLHR</i>, <i>ZYG11A</i>, and <i>GPR158</i>). A linear combination of the 10 methylation sites was used to calculate a “DNA methylation age”. <b>Results</b>: The 10-CpG clock’s predictions were highly correlated with chronological age (r = 0.80, R2 = 0.64), with a mean absolute error of ~5.5 years. Its performance, while slightly less precise than Horvath’s or Hannum’s multi-CpG clocks, is notable given the minimal marker set. It was observed that all 10 clock CpGs undergo age-related hypermethylation. The biological significance of these loci is discussed, along with the potential health and forensic applications of a saliva-based epigenetic age predictor. <b>Conclusions</b>: This study demonstrates that a saliva-specific epigenetic clock using only 10 CpG sites can capture a substantial portion of age-related DNA methylation changes, providing a cost-effective tool for age estimation. |
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| ISSN: | 2673-8856 |