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Unlocking the Secrets of Epigenetic Clocks: Novel Insights from Public Data

Discover the cool and potentially far-reaching consequences of Horvath's groundbreaking paper on epigenetic clocks, using public domain data from Illumina methylation arrays across various tissues, including cancer datasets. With a statistical method and predictive regression model, the study unveils a reset clock in iPS and ES cells, non-linear tick rate, and heritability of age acceleration. The findings suggest that epigenetic clocks are evolutionary conserved, heritable, and predictive of chronological age across healthy tissues. Explore the implications for ageing, diseases, genetic studies, and forensics.

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Unlocking the Secrets of Epigenetic Clocks: Novel Insights from Public Data

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Presentation Transcript

  1. Why this paper? Cool stuff Potentially far-reaching consequences Of relevance to our own work

  2. Take-home message Novel and important science can be done using data that are in the public domain

  3. Horvath paper: data • 7844 non-cancer samples from 82 datasets • Illumina 27k or 450k methylation arrays • 51 tissues / cell types • Also cancer Genome Atlas (TCGA) datasets • 21369 CpGs (probes) studied • overlap of the two arrays

  4. Statistical method • chronological age = CpG + noise • Training set of 39 datasets, rest Test • Penalised regression model (‘elastic net’) • 353 CpG selected in the model = ‘epigenetic clock’ • Predictor = DNAm age

  5. Measuring predictive accuracy • Age correlation • r(age, DNAm age) • Median error • median |DNAm age – chronological age| • Age acceleration • {DNAmage – chronological age}

  6. A multi-tissue age prediction works remarkably well

  7. A multi-tissue age prediction works remarkably well (test data)

  8. Epigenetic clock is reset in iPS and ES cells

  9. The clock tick rate is non-linear: fast until adulthood

  10. Age-acceleration is heritable!

  11. In cancers: more somatic mutations = less age acceleration

  12. Conclusions • There is an epigenetic clock • ~similar across healthy tissues • reset each generation and reset in iPS/ES cells • heritable • evolutionary conserved • Predictions of chronological age are reasonably accurate

  13. Discussion • Is DNAm Age a marker or effector of ageing? • What is DNAm Age a biomarker for? • Applications • Genetic studies • heritability, GWAS • Association • disease (dementia?) • gene expression? • Forensics

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