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Concept
Epigenetic clock
Summary
An epigenetic clock is a biochemical test that can be used to measure age. The test is based on DNA methylation levels, measuring the accumulation of methyl groups to one's DNA molecules.
The strong effects of age on DNA methylation levels have been known since the late 1960s. A vast literature describes sets of CpGs whose DNA methylation levels correlate with age. The first robust demonstration that DNA methylation levels in saliva could generate age predictors with an average accuracy of 5.2 years was published by a UCLA team including Sven Bocklandt, Steve Horvath, and Eric Vilain in 2011 (Bocklandt et al. 2011). The laboratories of Trey Ideker and Kang Zhang at the University of California, San Diego published the Hannum epigenetic clock (Hannum 2013), which consisted of 71 markers that accurately estimate age based on blood methylation levels. The first multi-tissue epigenetic clock, Horvath's epigenetic clock, was developed by Steve Horvath, a professor of human genetics and biostatistics at UCLA (Horvath 2013). Horvath spent over 4 years collecting publicly available Illumina DNA methylation data and identifying suitable statistical methods.
The personal story behind the discovery was featured in Nature. The age estimator was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. The major innovation of Horvath's epigenetic clock lies in its wide applicability: the same set of 353 CpGs and the same prediction algorithm is used irrespective of the DNA source within the organism, i.e. it does not require any adjustments or offsets. This property allows one to compare the ages of different areas of the human body using the same aging clock. Shortly afterwards, a derivation of Horvath's clock, the IEAA (Intrinsic Epigenetic Age Acceleration), an estimator based on the cellular composition of the blood, was developed.
A second generation of epigenetic clocks emerged a few years later and improved on the first in age estimation.
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