Epigenetic Tests for Biological Age
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Biological age tests are popular in the biohacking and longevity spheres - everyone wants to be able to brag that they have a much younger biological age than their chronological age! Essentially, biological age tests try to estimate your overall health - how much your healthy lifestyle is benefiting you and whether you are beating back the aging process.
Some tests look at telomere length or blood biomarkers, but a popular option is to look at epigenetic clocks. The epigenetic clock tests use DNA methylation data to estimate biological age.
First, some background on epigenetics, methylation, and circadian rhythms - just skip ahead if you know all this.
What is epigenetics — and what is DNA methylation?
Your cells all have the same genes in the nucleus, and DNA methylation is one way that genes are marked so that they aren't transcribed into their protein. There are several other ways that cells can turn genes on or off, but methylation is one that can be measured in these biological age tests and correlates with aging.
Essentially, all 20,000+ genes don't need to be translated into their proteins all the time. For example, your pancreatic cells don't need to make digestive enzymes all night long when you're sleeping instead of eating. Epigenetics is also the way that different genes are turned on or off in different types of cells - your liver doesn't need to make the same molecules as your brain cells. So there are many ways to mark segments of DNA (genes) to be transcribed into their proteins - or to block genes from being transcribed.
Epigenetics and circadian rhythm
Your circadian clock controls what happens in your body at different times of the day. Many things - such as cortisol, testosterone, and melatonin - fluctuate in a 24-hour rhythm.
In fact, some researchers estimate that about 40% of genetic transcription is under circadian control. For example, your body doesn't need to ramp up its immune response while you're asleep because you're not normally exposed to pathogens. Other processes are ramped up at night, when people are normally asleep. (Here’s a review of recent circadian rhythm studies on immune response and sports performance, if you want to learn more.)
The methylation cycle changes over the course of 24 hours:
When genes are methylated, they are marked with a methyl group so that they won't be transcribed. Methyl groups are produced in the methylation cycle and SAMe is the molecule that donates the methyl groups. The availability of SAMe and methyl groups is controlled by a feedback loop with SAH using the AHCY gene. Relevant here - AHCY interacts with the core circadian clock genes to increase methyl groups at certain times of the day. Here’s a longer explanation: AHCY genetic variants (Genetic Lifehacks article)
With the knowledge in hand that the overall availability of methyl groups rises and falls over the course of a day, let’s dive into this new study on how biological age tests vary depending on the time of day.
A recent study on biological age tests:
In a new study in Aging Cell, researchers look at the changing results of biological age tests over the course of a day.
The researchers tested several biological age models (Horvath, GrimmAge, etc.) at different times of the day using blood samples taken from an individual every three hours. They found that for some biological age models, the results were quite different depending on the time of day the blood sample was taken. For one biological age model, there was about a five-year difference in age between noon (older) and midnight (younger)! The researchers found that for the Hovarth clock, about 17% of the epigenetic sites oscillated over the course of 24 hours.
Here’s one of the figures from the study to give you a visual idea of what is going on:
The researchers point out that part of what is being measured are immune system players such as natural killer cells, T lymphocytes and B cells. These cell types are known to fluctuate throughout the day. Again, your immune response doesn't need to be on high alert when you're sleeping and not interacting with other people, so your body uses energy and resources at night to prioritize other cellular processes.
The practical takeaway here:
If you want to be your biological age youngest, take the test at night or early in the morning. If you take the test at noon, you'll show up older. Most importantly, if you want to compare your biological age test results to a previous test, make sure you take the tests at the same time of day.
For example, if you’ve been taking a super-duper expensive anti-aging supplement, you may want to take a biological age test before starting the supplement and then again six months later to see if the supplement works. Say you took the first test at noon and it came back saying that your biological age is 50. Then you take the test again months later, this time at 6 pm, and it shows that your biological age dropped to 48. You may think that the expensive supplement is working and your age has been reversed by 2 years. Yay! But in reality, the test differences could just be due to the time of day you took the test. Or maybe the supplement is working a little. Who knows?
Want to take a Biological Age test?
If this discussion of biological age has you itching to take one of these tests, here are a couple of options that are available via Amazon.
Personally, I haven’t used either of these tests. However, this newsletter was prompted by my digging into the research on global hypomethylation, circadian rhythm, and cancer, though, so I may give one of these tests a try sometime soon. To be honest, I don’t know how I would apply the information if I did the test…
Bigger picture:
Biological age tests and methylation tests aside, it is important to remember that many of your blood metabolites and other markers will rise and fall over the course of the day and night. If you want to compare your test results for any parameter, it's a good idea to always take the test at the same time of day.
If you're getting a vaccination or chemotherapy, timing is also important. Studies show that for some vaccines, the immune response is better based on circadian timing. Similarly, there are now a number of studies on how circadian rhythm affects your response to chemotherapy - definitely something to discuss with your oncologist if you ever find yourself in the situation of needing chemo.