Chapter 15
The Epigenetic Clock
We used to believe that once cells mature and their DNA is properly methylated to lock them into their specialized functions, that was that. Today we know that our “epigenome,” the pattern of methylation marks in cells, is a dynamic system and responds to stimuli from the outside. Epigenetics allows organisms to adapt more quickly to changing environmental conditions.
It can take eons for large-scale changes in the genetic code to occur, but existing genes can be turned on and off within hours. Epigenetics is at work when green grasshoppers turn black after a fire to better camouflage themselves against the charred ground, and when our bodies decide on the number of active sweat glands in the skin depending on whether we were born in the tropics or in a colder region. Epigenetics is a good thing. It means DNA does not write our fate in stone. Completely regardless of our family history, our decision to adopt a lifestyle can turn some of our genes on or off, affecting not only us but also our children and perhaps even grandchildren.
In the study “Gene Expression Modulation by Intervention with Nutrition and Lifestyle” (GEMINAL), Dr. Dean Ornish and colleagues took tissue biopsies before and after participants made intensive lifestyle changes for three months, which included a whole-food, plant-based diet. The scientists found beneficial changes in gene expression in 500 different genes. The expression of disease-preventing genes was promoted, and oncogenes that, for example, fuel breast and prostate cancer were suppressed. No matter what genes we inherited from our parents, we can influence how those genes affect our health through our diet and lifestyle. That is the power of epigenetics. The same DNA, but different outcomes.
The most impressive example of the epigenetic effects of diet on lifespan comes from the humble honeybee. Queens and workers are genetically identical, yet queens can live three years and lay up to 2000 eggs daily, whereas workers live only three weeks and are functionally sterile. How is that possible if they do not differ genetically? They eat differently. When a swarm’s queen dies, nurse bees select a larva and feed it a secretion called royal jelly. (The workers are usually fed only a mixture of honey and pollen that bears the delightful name bee bread.) When the selected larva eats this jelly, the enzyme that had suppressed the queen genes is switched off, and a new queen emerges. The queen has the exact same genes as every worker, yet simply through what she eats, different genes are expressed, resulting in dramatic changes in her life and lifespan. A 50-fold increase in life expectancy, thanks to epigenetics.
Royal living?
If royal jelly can turn a simple larva into a queen that lives more than 50 times longer, shouldn’t we consider eating royal jelly ourselves? At see.nf/royaljelly I go through the available evidence. Spoiler alert: While it’s the greatest thing for bees, in rare cases humans develop hemorrhagic (bloody) inflammation of the intestines after taking dietary supplements containing royal jelly. So if you spread royal jelly on your peanut butter sandwich, it can royally backfire.
The epigenetic clock
Our chromosomes have certain DNA sites that, over the course of life, are predictably methylated or demethylated like clockwork, thus constituting a “molecular crystal ball for human aging.” In a remarkable triumph of data analysis, from the millions of methylation sites in our DNA, a small subgroup shifts over time so reliably that one can predict a person’s age within a few years simply by strategically measuring the methylation pattern at a few hundred—or even only a few dozen—sites, in a human genome that comprises three billion genetic letters.
In the last few years, these “epigenetic clocks” have proven to be a reliable measure of chronological age and have displaced telomere length (see the chapter on telomeres) as the best indicator of age. Why invent an expensive, unnecessarily complicated test to estimate someone’s age when you could just ask them? Well, one can imagine forensic applications such as determining the age of an unidentified victim from a blood or tissue sample, but that only scratches the surface. The key point is that epigenetic clocks measure not only our chronological age but apparently our true biological age as well. In other words, our epigenetic age predicts our remaining lifespan more accurately than the calendar does. Check out see.nf/clock to get the whole wild story.
It’s like science fiction. Put a drop of blood into a futuristic machine that measures the placement of chemical markers on a strand of DNA, and it spits out your true age, reflecting the entire story of your lifestyle choices. Beyond predicting the remaining time until death, epigenetic clocks also appear to indicate markers of healthspan, such as cognitive decline, frailty, arthritis, and the progression of diseases like Alzheimer’s and Parkinson’s. As you can imagine, the insurance industry has pounced on this, and soon your epigenetic age could determine your premiums. But this isn’t the carved-in-stone curse of a fortune-teller. You can change the pace at which you age and may soon be able to measure your progress using epigenetic clocks—potentially a radically faster and cheaper way to test anti-aging interventions.
Aging biologically faster or slower
Studies of centenarians show that some age so slowly that a 105-year-old can have the DNA-methylation age of a 60-year-old. No wonder he lives so long! What can we do to slow down our epigenetic clock and slow aging? Analyses of epigenetic clocks show that women age more slowly than men, which makes sense, since women generally live longer—a pattern so robust that one population researcher joked, “Being a man is an inherited disease.” To catch up, men have to make even healthier changes in their diet and lifestyle.
Cigarette smoke is linked to accelerated biological aging and has a pronounced effect, even when exposure is only slight. In contrast, both the frequency and the intensity of exercise are associated with a slowing of the aging process. And meditating? Two months of daily practice did not significantly affect aging rates, and people who meditate long-term age at the same pace as control participants who do not meditate. Practitioners who average 6000 hours of meditation may nevertheless reduce the acceleration of epigenetic aging over time.
Until recently, calorie restriction had not yet been tested in humans, but we already knew it slows epigenetic aging in mice and monkeys. Over 15 to 20 years with 30 percent less food, middle-aged rhesus macaques appeared to age epigenetically seven years less. And even more dramatic: mice with a 40-percent calorie reduction seemed to get only about one year older over roughly three years. In 2018, the analysis of aging from the CALERIE study was published. In this first large randomized study on calorie restriction in humans, biological aging was determined with non-epigenetic estimates. The control group continued to age at a rate of about one year per year, but over the same period the dietary-restriction group seemed to age only one month. And that with a calorie restriction of only 12 percent, which corresponds to about one donut less per day.