Epigenetic clock

An epigenetic clock is a type of DNA clock based on measuring natural DNA methylation levels to estimate the biological age of a tissue, cell type or organ. A pre-eminent example for an epigenetic clock is Horvath's clock, which is based on 353 epigenetic markers on the human genome.

The strong effect of age on DNA methylation levels has been known since the late 1960s. A vast literature describes sets of CpGs whose DNA methylation levels correlate with age, e.g. Two publications describe age estimators based on DNA methylation levels in either saliva or blood.

Horvath's epigenetic clock was developed by Steve Horvath, a professor of human genetics at the David Geffen School of Medicine at UCLA and of biostatistics at the UCLA Fielding School of Public Health. The scientific article was first published on Oct 21, 2013, in Genome Biology. 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.

It is not yet known what exactly is measured by DNA methylation age. Horvath hypothesized that DNA methylation age measures the cumulative effect of an epigenetic maintenance system but details are unknown. The fact that DNA methylation age of blood predicts all-cause mortality in later life strongly suggests that it relates to a process that causes aging. However, it is unlikely that the 353 clock CpGs are special or play a direct causal role in the aging process. Rather, the epigenetic clock captures an emergent property of the epigenome.

In general, biological aging clocks and biomarkers of aging are expected to find many uses in biological research since age is a fundamental characteristic of most organisms. Accurate measures of biological age (biological aging clocks) could be useful for

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