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Horvath's clock estimates the chronological age of people based on the methylation of 353 CpG sites. It is noted for its unprecedented accuracy (median error of 3.6 years) and consistency across multiple tissue sources.

I learned that changes in DNA methylation were primarily caused by the cellular environment, so patterns of DNA methylation in specific cell types can be linked to diseases like atherosclerosis and cancer. If this holds true, does Horvath's clock suggest that there is a global mechanism controlling methylation of these 353 CpG sites? It seems unlikely that distant tissue regions subject to different cellular environments would converge by chance.

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