What is DNA methylation?
Your DNA is the same in almost every cell of your body. What differs is which genes are active. One of the mechanisms that regulates this is DNA methylation: small chemical groups (methyl groups) attached to specific sites on the DNA, mostly where the letter C is followed by a G (so-called CpG sites).
Methylation does not change your genetic code. But across the human genome, the methylation level at many of these sites shifts in characteristic ways as we get older.
What is an epigenetic clock?
An epigenetic clock is a mathematical model that combines the methylation levels at hundreds of CpG sites into a single estimate. Researchers develop these models on large groups of people and publish them, so other scientists can test and use them.
The result is called biological age or epigenetic age: an estimate of age based on molecular patterns, rather than on your date of birth.
The four clocks we use
We compute four clocks, because each was developed with a different goal and on different data. Showing them side by side gives a fuller picture than any single number.
Horvath (2013)
The first epigenetic clock that works across many tissues and cell types. It was trained to estimate chronological age and uses 353 CpG sites.
PhenoAge (2018)
A second-generation clock. Instead of being trained on age in years alone, it was developed using a “phenotypic age” built from a set of clinical blood markers. It uses 513 CpG sites.
GrimAge (2019)
A second-generation clock that combines methylation-based estimates of several plasma proteins and of smoking history into one estimate.
DunedinPACE (2022)
Rather than an age, DunedinPACE estimates your current pace of aging: how many years of biological aging you experience per calendar year. A value of 1.0 corresponds to the average pace in the research cohort it was developed in. It is based on the Dunedin Study, which followed the same group of people born in 1972–73 in New Zealand for decades and tracked changes in 19 biomarkers over 20 years.
How we measure
We measure methylation at more than 900,000 CpG sites with an Illumina EPIC array, the technology used in much of the research behind these clocks. Our own analysis pipeline then computes each clock as published.
What the clocks can and cannot tell you
- They are estimates. Different clocks give different values for the same person. That is expected, not a contradiction.
- Every measurement varies. Like any lab measurement, results include some technical variation. A difference of a year or two between two tests is not necessarily meaningful. Your report explains this.
- They describe groups better than individuals. The clocks were validated in large studies. For one person, a single result is a snapshot, not a verdict.
- They are not a diagnosis. zeitlens is a wellness service and not a medical device. The test is not intended to detect, predict, monitor or treat any disease.
Sources
- Horvath S. DNA methylation age of human tissues and cell types. Genome Biology. 2013;14:R115. doi:10.1186/gb-2013-14-10-r115
- Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging. 2018;10(4):573–591. doi:10.18632/aging.101414
- Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging. 2019;11(2):303–327. doi:10.18632/aging.101684
- Belsky DW, Caspi A, Corcoran DL, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022;11:e73420. doi:10.7554/eLife.73420
- Higgins-Chen AT, Thrush KL, Wang Y, et al. A computational solution for bolstering reliability of epigenetic clocks. Nature Aging. 2022;2:644–661. doi:10.1038/s43587-022-00248-2