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You probably know people who seem to age faster or slower than their birthday says. Two friends the same age, and one looks and feels ten years older. That difference is written into your cells, in a pattern of chemical tags on your DNA called methylation. The pattern shifts so predictably with age that it can be read like a clock, and in some people the clock runs fast. Your cells also have a way to erase those tags. Understanding how the tags are written and removed explains what pushes your clock forward, and what might slow it down.

Your DNA keeps a clock

Your genes don’t change much over your life, but how they’re switched on and off does. One of the main switches is methylation: small chemical tags called methyl groups attached to your DNA. A methyl tag near a gene usually keeps that gene quiet.

As you age, the pattern of these tags changes in a remarkably consistent way. Measuring methylation at a few hundred spots on your DNA can estimate your age, and this measure is called your biological age or epigenetic age. It reads close to zero in embryonic stem cells and runs well ahead of actual age in cancer tissue.¹

Biological age matters because it predicts health better than the calendar does. One of these clocks, known as GrimAge, predicts lifespan, heart disease and cancer, and it runs faster in people with fatty liver and excess abdominal fat.² So if your clock runs ahead, that’s a signal worth paying attention to.

Methylation: writing the tags

Your cells add methyl tags to DNA using enzymes called DNMTs. They draw the methyl groups from SAMe, the molecule your methylation cycle makes from folate, B12 and the amino acid methionine. Every time a cell divides, these enzymes copy the pattern onto the new DNA, so the cell remembers which genes should stay off.

If SAMe runs short, the tags aren’t copied properly and DNA becomes under-methylated. Even a marginal shortfall of folate in the diet lowered DNA methylation in women’s white blood cells, and it recovered when their folate intake went back up.³ That’s one reason methylation keeps coming up in my work, and why high homocysteine makes everything worse.

Demethylation: the eraser

For a long time, scientists assumed methyl tags could only be lost passively, by not being copied when a cell divides. Then a family of enzymes called TET was found to remove them actively. TET enzymes convert the methyl tag (5-methylcytosine, or 5mC) into a different tag called 5-hydroxymethylcytosine (5hmC), which is then cleared away.⁴

Your body uses this eraser in some of its most important moments:

  • Just after conception, when most of the tags inherited from the parents are wiped so the embryo can start with a clean slate.
  • In the cells that will become eggs and sperm, which are reset before being passed on.
  • In the brain, where 5hmC is unusually abundant, particularly in the Purkinje cells of the cerebellum that coordinate movement.⁵

So demethylation isn’t the opposite of healthy methylation. The two work together. Methylation writes the instructions, and demethylation lets cells edit and reset them.

 

Demethylation and ageing

Rewinding the clock in mice

Here’s what makes demethylation so interesting for ageing. Researchers switched on a set of reprogramming genes in the eye nerve cells of old mice. Those cells regained youthful methylation patterns, their damaged nerve fibres regrew, and the old mice recovered lost vision. This worked only when two TET enzymes, TET1 and TET2, were present.⁶

That tells us two things. Ageing cells still keep a record of their youthful pattern, and the TET eraser is part of how they get back to it. This is gene therapy in mice, not something you can do at home. But it shows the clock isn’t only a one-way street.

What your eraser enzymes need

TET enzymes need iron and oxygen to work, along with alpha-ketoglutarate, a molecule made in the Krebs cycle inside your mitochondria.⁷ Vitamin C helps them work by keeping their iron in its active form, and adding vitamin C to stem cells quickly raised 5hmC and removed methyl tags across many genes.⁷˒⁸ Vitamin A switches on the genes for two TET enzymes, TET2 and TET3.⁸

The link to alpha-ketoglutarate is the part I find most interesting, and this is my interpretation. Because the eraser depends on a molecule made by the Krebs cycle, strained mitochondria may also mean a slower eraser. It’s another way energy production and gene regulation are tied together. I’ve covered how the Krebs cycle works in sugar, fat or ketones: which gives your cells more energy.

Nutrient Role Food sources
Folate Makes SAMe for writing methyl tags Leafy greens, legumes, liver, eggs
Vitamin B12 Makes SAMe for writing methyl tags Meat, fish, eggs, dairy
Methionine, serine, glycine Raw material for the methylation cycle Meat, chicken, fish, eggs, legumes
Vitamin C Keeps TET enzymes active Citrus, kiwifruit, capsicum, broccoli, Brussels sprouts, guava, parsley, blackcurrant
Iron Built into TET enzymes Red meat, liver, legumes, dark leafy greens
Vitamin A Switches on TET2 and TET3 Liver, egg yolk, butter, cod liver oil (carrots, sweet potato and leafy greens supply beta-carotene)
Oxygen Used by TET enzymes Regular movement, good circulation

More iron isn’t always better. Too much iron drives oxidative stress, and some people react badly to it (see why iron can make you feel worse). The aim is enough, not extra.

 

Demethylation and ageing

When the eraser fails: blood, heart and cancer

As we age, some of our blood stem cells pick up gene changes and expand into larger groups of identical cells. This is called clonal haematopoiesis, and it’s common in older people. TET2 is one of the genes most often affected. People carrying these changes have almost twice the risk of heart disease, and in mice, blood cells lacking TET2 drove larger artery plaques by ramping up inflammation.⁹˒¹⁰ It’s a striking example of an epigenetic enzyme linking ageing to what actually damages your arteries.

Cancer shows the same pattern. 5hmC is missing from cancer cell lines,⁵ and in the most common type of ovarian cancer, a global loss of 5hmC was linked with poorer response to chemotherapy, earlier relapse and shorter survival. Restoring 5hmC made resistant cancer cells sensitive to chemotherapy again in the lab and in animals.¹¹ In leukaemia models with faulty TET2, vitamin C mimicked restoring TET2 and slowed the disease.¹²

These are research findings, not treatments. They show how central the eraser is to keeping cells behaving normally.

Can lifestyle change your biological age?

This is the question everyone asks, and the honest answer is: possibly, a little, and we’re still finding out.

  • An eight-week diet and lifestyle programme in healthy men in their 50s to 70s focused on methylation-supporting foods, sleep, exercise and relaxation, with a probiotic and a plant-nutrient powder. Their biological age came out about three years younger than a control group’s, on one epigenetic clock. Their folate levels rose and their triglycerides fell.¹³ It was a small pilot study using a single clock, so it needs repeating, but it’s an encouraging start.
  • Eating less for two years, aiming for about a quarter fewer calories, slowed the pace of ageing measured by one clock in healthy adults. Other clocks didn’t change, and the effect was small.¹⁴

So the evidence suggests the clock can be nudged, mostly through the same things that support methylation and mitochondria: good nutrition, not overeating, movement, sleep and managing stress.

Should you test your biological age?

Biological age tests are now sold directly to the public. They can be interesting, but be careful how you read them. Some widely used clocks gave results up to nine years apart on the same sample, purely from technical noise.¹⁵ Newer versions are more consistent, but a change of a year or two between tests may mean nothing.

If you do test:

  • Ask which clock the company uses and how reliable it is on repeat testing.
  • Use the same company and the same clock each time.
  • Look for trends over a year or more, not week-to-week changes.
  • Treat it as one signal alongside how you feel and your other results, not a verdict.

What supports your methylation and demethylation

  • Eat a varied, whole-food diet with plenty of leafy greens, colourful vegetables and fruit, and enough protein.
  • Don’t overeat. Constant fuel overload strains the mitochondria that supply the eraser.
  • Move every day, for circulation and oxygen supply.
  • Keep alcohol low. It drains the same methylation and energy pathways.
  • Protect your sleep and manage stress.
  • Check homocysteine if you’re concerned about methylation. It’s a useful window into how well the cycle is running.

Frequently asked questions

What is biological age?
Biological age is an estimate of how old your body is, based on patterns of methylation tags on your DNA. These patterns change predictably with age, and when your biological age runs ahead of your actual age, it predicts higher risk of disease and earlier death.

What is the difference between methylation and demethylation?
Methylation adds small chemical tags to DNA that usually switch genes off. Demethylation removes them, either passively when tags aren’t copied during cell division, or actively through TET enzymes. Healthy cells need both to write and edit their genetic instructions.

What are TET enzymes?
TET enzymes actively remove methyl tags from DNA. They convert 5-methylcytosine into 5-hydroxymethylcytosine, which is then cleared. They need iron, oxygen and alpha-ketoglutarate to work, and vitamin C helps keep them active.

Can you lower your biological age?
Early evidence suggests it can be nudged. A small eight-week diet and lifestyle programme lowered biological age by about three years on one clock, and two years of eating less slowed the pace of ageing. Larger, longer trials are still needed.

Does vitamin C affect DNA methylation?
In the lab, vitamin C boosts TET enzyme activity and helps remove methyl tags, because it keeps the enzymes’ iron in its active form. How much dietary vitamin C influences this in people isn’t yet clear.

Are biological age tests accurate?
They vary. Some clocks gave results years apart on the same sample because of technical noise, although newer versions are more reliable. Use the same test each time and look at long-term trends rather than small changes.

References

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2. Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019;11(2):303-327. PMID 30669119.

3. Jacob RA, Gretz DM, Taylor PC, et al. Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J Nutr. 1998;128(7):1204-1212. PMID 9649607.

4. Tahiliani M, Koh KP, Shen Y, et al. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science. 2009;324(5929):930-935. PMID 19372391.

5. Kriaucionis S, Heintz N. The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science. 2009;324(5929):929-930. PMID 19372393.

6. Lu Y, Brommer B, Tian X, et al. Reprogramming to recover youthful epigenetic information and restore vision. Nature. 2020;588(7836):124-129. PMID 33268865.

7. Blaschke K, Ebata KT, Karimi MM, et al. Vitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells. Nature. 2013;500(7461):222-226. PMID 23812591.

8. Hore TA, von Meyenn F, Ravichandran M, et al. Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms. Proc Natl Acad Sci U S A. 2016;113(43):12202-12207. PMID 27729528.

9. Jaiswal S, Natarajan P, Silver AJ, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377(2):111-121. PMID 28636844.

10. Fuster JJ, MacLauchlan S, Zuriaga MA, et al. Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice. Science. 2017;355(6327):842-847. PMID 28104796.

11. Tucker DW, Getchell CR, McCarthy ET, et al. Epigenetic reprogramming strategies to reverse global loss of 5-hydroxymethylcytosine, a prognostic factor for poor survival in high-grade serous ovarian cancer. Clin Cancer Res. 2018;24(6):1389-1401. PMID 29263182.

12. Cimmino L, Dolgalev I, Wang Y, et al. Restoration of TET2 function blocks aberrant self-renewal and leukemia progression. Cell. 2017;170(6):1079-1095. PMID 28823558.

13. Fitzgerald KN, Hodges R, Hanes D, et al. Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging (Albany NY). 2021;13(7):9419-9432. PMID 33844651.

14. Waziry R, Ryan CP, Corcoran DL, et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nat Aging. 2023;3(3):248-257. PMID 37118425.

15. Higgins-Chen AT, Thrush KL, Wang Y, et al. A computational solution for bolstering reliability of epigenetic clocks: implications for clinical trials and longitudinal tracking. Nat Aging. 2022;2(7):644-661. PMID 36277076.