It’s the perfect time to dive into the topic of methylation and biological aging as the first results of the years-in-the-making, first-of-its-kind study I’ve been working on has just been published in the prestigious peer-reviewed journal – Aging. Personally, I couldn’t be more delighted as it’s the perfect home for this particular paper, which you can find here.
There’s a lot unpack on the connection between DNA methylation and biological aging–the rate at which our body ages physically–but if you’re interested in reversing biological aging, extending healthspan, and reducing the risk of disease and death it’s time to get caught up.
Aging is the number one risk factor for chronic disease.
Chronological vs. Biological Age
Chronological age is the time that has passed since you were born. It’s the number you celebrate each year on your birthday and is the primary way we define our age.
We know that increased chronological age is a rough predictor of chronic disease and mortality (ok, beyond a certain point, it’s an excellent predictor of mortality). However, what’s even better at predicting chronic disease and mortality risk is your biological age. In fact, it is the number one predictor. And that’s because biological age is a numerical assessment of the level of damage and loss of function that your cells, tissues, and organs have accumulated. This damage is what turns into disease.
Scientists are very interested in being able to determine and reduce your biological age because doing so reduces the risk of chronic disease and death.
Slowing or even reversing biological aging offers a compelling opportunity to improve healthspan—to make the years we live, especially our older years, more likely to be disease-free and fulfilling. Aging and diseases of aging are also the biggest risk factor for Covid-19, expanding the importance of biological aging beyond chronic disease and making it acutely relevant to the most high-profile current health problem.
On a personal level, I’m deeply motivated to tackle biological aging, being the 50-something-year-old adoptive mother of a toddler whom I want to see through as many life milestones as possible. Most people I know similarly want to preserve their health for as long as they can.
How We Can Measure Biological Age
To understand the ways we can measure biological age and to connect the dots between biological aging and DNA methylation—which, as its name suggests, is the addition and removal of methyl groups to strands of DNA—we must step back and look at some of the giant scientific leaps made in the last two decades. One of the most exciting has been our increasing understanding of epigenetics.
Epigenetics is the biochemical layer described as sitting on top of our DNA, regulating how genetic material is read. Depending on the epigenetic patterns on a particular gene, that gene may be “turned on” (i.e., actively being read and used), or “turned off” (i.e., shut down and silent). Genes you might want to be turned on are those like tumor-suppressor genes, which fight cancer, and those you might want to be turned off, or at least down, are those that promote inflammation. Yet this is the exactly opposite of what happens to these genes as our biological age grows higher. It’s almost as if we’re programmed for disease. Unless we can find a way to slow or reverse the aging process itself.
By far the most prominent, and most well-researched, biochemical epigenetic mechanism is DNA methylation, which involves the addition of a tiny “methyl group” (simply one carbon with three hydrogens attached) to a cytosine base exposed on the DNA strand.
DNA methylation is the most well-studied epigenetic mechanism and is deeply connected to biological aging.
DNA methlyation patterns have recently been shown to predict biological age with incredible accuracy. Just a few years ago, in 2013, Dr. Steve Horvath, one of the foremost epigenetic researchers, published a tremendously exciting paper. In it, he laid out the work he and his team at UCLA had done to predict human age by measuring the methylation status of 353 cytosine sites on our DNA and do it significantly more than telomere length and metabolic biomarkers.
Other scientists also began to publish their own epigenetic age predictors, and collectively these became known as “epigenetic clocks” or “biological clocks.” They are the best method we have to determine biological age.
And they can also help us assess how our health interventions are impacting our aging.
The Evidence That Biological Age is Modifiable
One of the most promising things about the field of epigenetics and biological clocks is that (unlike our underlying genes) epigenetic patterns are modifiable. And many DNA methylation sites respond readily to certain environmental inputs.
We first began to understand the power of DNA methylation 10 years before Horvath’s paper, thanks to a study conducted by Robert Waterland and Randy Jirtle the results of which were published in what is now the most-cited scientific study of all time.
In this mouse study, Waterland and Jirtle showed that using methylation-supportive nutrients could alter genetic expression to such an extent that it could be visible to the naked eye. In this case, it altered the coat color and bodyweight of the offspring of mice, who had all been bred with a particular gene (the “agouti” gene) that promotes yellow fur and obesity. Giving the mouse mothers folate, B12, choline, and betaine–all nutrients that provide ingredients needed for DNA methylation–led to reduced agouti gene expression in the offspring. In one generation, the agouti mice went from yellow and obese to brown and at a healthy weight. In short, DNA methylation-supportive nutrients silenced the gene that causes yellow fur and obesity in these mice. This is really incredible when you think about it as it shows the impact of nutrition on gene expression, and the influence of that impact across generations. From this study, we can conclude that nutrition powerfully and directly influences genetic expression across generations. Wow.
While this was great news, we still needed to learn how to use these nutrients safely. Since the agouti mouse study, many other studies started to emerge that showing using very high doses of methylation nutrients (like folate and B12) could have unwanted side effects. Some research showed that cancer cells, for instance, could potentially harness some of these nutrients to contribute to its growth. Thus, more DNA methylation isn’t always better. Although we haven’t entirely thrown out higher doses of methyl donor nutrients in my clinic, since some clinical conditions do respond extremely well to that kind of protocol, we approach it in a highly nuanced and careful way, and we look to diet to provide the vast majority of those nutrients—something the research thus far has shown to be safe.
Homing in on Biological Age Change
More recently, researchers (and now I count myself among them) have started to investigate whether we can change DNA methylation in a way that favorably impacts epigenetic age and thereby increase lifespan and reduce the risk of disease and early death.
When my team and I embarked on our DNA methylation study, there were no published results that addressed whether we can change DNA methylation in a way that favorably impacts epigenetic age in humans. Even now, there are just four. One of which–#4, below–is our own DNA methylation study:
- Chen et al. (2019) who showed that Vitamin D3 used at a dose of 4,000 IU/d for 16 weeks in overweight/obese African Americans with vitamin D deficiency (25(OH)d <50 nmol/L) decreased epigenetic age by 1.85 years.
- Fahy et al. (2019) who gave participants a daily injection of growth hormone plus a prescription drug and three nutritional supplements for an entire year and identified a reduction in epigenetic age of 1.5 years plus the study duration (totaling 2.5 years).
- Gensous et al. (2020) who analyzed a set of data from a previous trial to identify a very small population subset who, after consuming a Mediterranean diet plus 400 IU/d vitamin D3 appeared to reduce epigenetic age by 1.47 years (other groups who followed the same regimen did not demonstrate an improved epigenetic age to a level of statistical significance).
- Fitzgerald et al. (2021) – the study I co-led which used a dietary and lifestyle intervention that combined known methyl donor nutrients from food as well as dietary and lifestyle factors with known influence on DNA methylation to form a comprehensive program directly targeted at optimizing epigenetic patterns. The results astounded us… participants in the intervention group reduced their epigenetic age by a statistically significant 3.23 years compared to the control group over just 8 weeks.
The Amazing Power of Food and Lifestyle Practices to Massage DNA Methylation
Our study provided greater results in a shorter amount of time than these other studies, I believe, because we have crafted an eating plan that is specifically designed to include a copious amount of the nutrients used in the methylation cycle—known as methyl donors—as well as the nutrients that regulate DNA methylation and help the body put the methyl groups in the right places and in the right amounts—known as methylation adaptogens. These two groups of foods include greens, cruciferous vegetables, clean animal protein, nuts, seeds, eggs, beets, and berries—healthy, delicious foods that are natural components of a low-glycemic, plant-based, keto-leaning diet. Better yet, this food-forward approach lets the body take these nutrients and use them according to its own inherent wisdom to balance DNA methylation. (As opposed to, say, telling the body what to do via injected hormones, prescription drugs, or administering high doses of the nutrients in supplement form.)
Coupling this eating plan with doable lifestyle practices, such as moderate exercise, decent sleep, connecting to others, and some sort of relaxation practice—all of which have been shown to favorably impact DNA methylation, too—maximizes the benefit to your biological age while also enriching your life.
My Own Journey In Reversing Biological Aging
As an aside, although I couldn’t take part as a participant in my own study, I have been tracking my own epigenetic age as I follow along with the intervention we used in the study. Just a few weeks ago I measured my DNAge (my epigenetic age), and I’m delighted to report that I’m at my youngest bio-age yet (relative to my chronological age)! I am now biologically younger than 82% of people my age (up from 50% at the last measure), and my number is more than 2 standard deviations away from the median age, meaning that my age difference isn’t due to chance.
Seeing these results is incredibly motivating and makes it mentally easy to continue. And I’m happy to report that my team and I are working on making these tests available to consumers, too–if you are interested in being one of our 100 beta testers who have early access to this testing, sign up here. I am also happy to be using an approach that is totally safe and does not involve medications (which can have side effects), and that I know is comprehensive and grounded in principles of healthy living and eating. It’s just amped-up to specifically target epigenetics in a very intentional way.
Start Your Journey Towards Youthfulness
Biological age reversal is now possible, and biological youthfulness is at your fingertips. If you’d like to find out more, here are two options for you:
Younger You walks you through the science behind gene expression and outlines the exact diet and lifestyle program that helped our study participants shave 3+ years off their biological age in only 8 weeks, as well as everyday recommendations that help you nourish your DNA methylation over the long-term.
With thanks to Romilly Hodges MS CNS for her contributions to this article.