Most of our cells have a genetic code that, when deciphered, tells our body how to make the proteins we need for survival. With the passing of time and experience of hardship, small modifications are added to act like ‘genetic switches’, affecting the way our cells interpret the instructions without changing the code itself.
Accumulations of these so-called epigenetic changes are often used to estimate the biological age of our cells and tissues. But researchers in Lithuania have now shown that the edits can fluctuate throughout the day, suggesting tests based on a single tissue sample aren’t as accurate as they could be.
The team studied multiple blood samples from a 52-year-old man taken every three hours over 72 hours, looking at 17 different epigenetic clocks within each specimen’s collection of white cells.
What they found was surprising. Thirteen of the 17 epigenetic clocks showed a substantial difference throughout the day, appearing ‘younger’ in the early hours of the morning and ‘older’ around midday, with relative differences equivalent to around 5.5 years’ worth of changes. This daily cycle is similar to what other scientists found in a 2020 study.
“The majority of the aging studies investigating epigenetic clocks use whole blood as the tissue of interest. However, experiments in our lab and from other groups have shown that white blood cell subtype counts and their proportions oscillate with a 24 hour periodicity,” statistician Karolis Koncevičius from Vilnius University and colleagues write in their published paper.
This means a single epigenetic test at one time of day might not give the whole picture.
Relying on just a single individual’s samples meant the team could focus on a single set of changes, at the cost of being able to generalize across a larger population. Further analysis of different blood samples taken over five hours from a small group also found age fluctuations, however.
Some of these cellular age changes might be because our blood contains different types of white blood cells at different times of the day. However, some measures still showed this age fluctuation even when the researchers focused on just one type of white blood cell.
The findings suggest that to get the most accurate picture of how old your cells are, scientists might need to take multiple samples at varied times of day in the future. A more complete measure of epigenetic age range might allow more precise predictions about risk of age-related diseases in populations too.
“Our findings indicate that age predictions of epigenetic clocks oscillate throughout the day,” the authors write. “Failure to account for daily oscillations may hamper estimates of epigenetic age.”
The research has been published in Aging Cell.
