What are epigenetic marks?

Almost every cell in your body carries the same DNA, yet a liver cell and a skin cell behave very differently. Part of the reason is epigenetic marks: chemical tags on the DNA that help decide which genes a cell uses.

The best-studied mark is DNA methylation, a small methyl group attached to the DNA letter C where it is followed by a G. These places are called CpG sites, and the human genome has about 28 million of them. A site can carry the tag in some of your cells and not in others, so a lab reports each site as a share between 0 and 100%.

Unlike your genetic code, methylation changes over your life. Identical twins are almost indistinguishable epigenetically when they are young, but older twins show clear differences (Fraga et al., 2005).

One site across five cells

The same stretch of DNA, A T C G T A, shown in five cells. The C of the CpG site carries a methyl tag in three of the five cells, so the site is 60% methylated. Methyl tag No tag Cell 1 Cell 2 Cell 3 Cell 4 Cell 5 ATCGTA ATCGTA ATCGTA ATCGTA ATCGTA 3 of 5 cells carry the tag 60% methylated

What a clock reports

A chart with age in years across and epigenetic age up. A diagonal line marks where epigenetic age equals age in years. Two people of the same age sit above and below the line: above means ageing faster, below means ageing slower. Epigenetic age Age in years Same as age in years Ageing faster above the line Ageing slower below the line
Left: at a CpG site, the letter C carries a methyl tag in some of your cells and not in others, so the lab reports a share, here 60%. Right: a clock combines many sites into one estimate. Above the line, your epigenetic age is higher than your age in years; below it, lower. Illustration, not real data.

What is an epigenetic clock?

As we age, methylation rises at some CpG sites and falls at others. An epigenetic clock is a model that reads methylation at a selected set of sites and turns it into an estimate of age.

The first widely used clocks were published in 2013. Gregory Hannum and colleagues built a clock from 71 sites in blood (Hannum et al., 2013), and Steve Horvath built one from 353 sites that works across 51 tissues and cell types (Horvath, 2013).

The clock’s estimate is often called your epigenetic or biological age. When it is higher than your age in years, your body shows more signs of ageing than expected. Researchers call the difference age acceleration.

From age to health

Later clocks were trained on signs of health as well as age. PhenoAge (513 sites) was built from routine blood tests, such as glucose and a marker of inflammation, and GrimAge (1,030 sites) from blood proteins and smoking history. Both predict lifespan and healthspan, the years lived in good health, beyond what your age in years can tell (Levine et al., 2018; Lu et al., 2019).

DunedinPACE (173 sites) takes a different approach. It was built from 19 biomarkers measured in the same people over 20 years, and it estimates how fast you are ageing now, in years of biological ageing per calendar year (Belsky et al., 2022).

Can it change?

Because methylation responds to how you live, your epigenetic age isn’t fixed. In a study of more than 4,500 people, eating more fish and more fruit and vegetables (measured as carotenoids in blood), more years of education and a lower body mass index all went with slower epigenetic ageing (Quach et al., 2017).

Trials are rarer. In the CALERIE trial, two years of moderate calorie restriction slowed the pace of ageing measured by DunedinPACE by 2–3%, while PhenoAge and GrimAge didn’t change significantly (Waziry et al., 2023).

The evidence is still young, and most of it comes from observational studies. That is one reason Senva is built around testing again: so you can follow your own change over time.

Why saliva?

Most clocks were built from blood, which means a needle or a finger prick. Saliva is easier: you can give it at home in a few minutes. In adults, it carries DNA from white blood cells and from cells lining the mouth in roughly equal shares (Theda et al., 2018), and one of the first epigenetic age predictors was built from saliva (Bocklandt et al., 2011).

Methylation patterns differ between cell types, so a clock trained on blood doesn’t automatically read saliva as well. Senva’s model is trained on saliva from the start.

How many sites does a clock need?

Published clocks use anything from a handful of sites to more than a thousand. Researchers estimate the age of wild humpback whales from a small skin sample using methylation in just three genes (Polanowski et al., 2014), and one universal clock works across 185 mammal species and 59 tissue types (Lu et al., 2023).

A compact set of sites can be measured with targeted lab methods, which keeps a test affordable. Senva’s model reads a small set of epigenetically relevant sites and is built to show how they relate to ageing and health, so your result can be explained, not just reported.

What a clock can’t tell you

An epigenetic age is an estimate, not a diagnosis. It says something about how your body is ageing on average, not whether you have or will get a particular disease. Senva is a wellness test: it helps you understand your health and what to work on. If you have health concerns, talk to your doctor.