How Old Are You Now?
BIOLOGICAL AGE VS. CHRONOLOGICAL AGE
Your chronological age increases at a steady pace for every trip around the sun. However, your “biological age” may speed up or slow down depending on how you live your life.
BIOLOGICAL AGE REFERS TO AN ESTIMATE OF HOW OLD YOU ARE ON A CELLULAR LEVEL AND DEPENDS ON COMBINATIONS OF GENETICS, LIFESTYLE, AND THE ENVIRONMENT THAT YOU LIVE IN.
As you move through adolescence into young adulthood, the pace of aging changes and your chronological age and biological age diverge.
Everyone knows that you cannot choose your parents and control the genes that you inherit. But scientists have learned that there are behavioural and environmental factors under your control that can play a fundamental role in how your genes work (gene expression) and subsequently, your biological age.
Lifestyle and the environment alter gene expression over time through cellular processes known as epigenetics, and “epigenetic clocks” are modern tools that allow us to study those changes to tell us about biological age.
From countless studies on lifestyle factors, we know that the most protection from healthy habits occurs when they’re adopted and sustained from a young age. But which habits will play the biggest role in keeping your cells young, and what’s the optimal “dose” for each lifestyle change? In the future, epigenetic clocks may help to answer these questions.
EPIGENETIC CLOCKS
To learn more about epigenetic clocks, Mind Over Matter® interviewed Dr. Calen P. Ryan, a research scientist at the Robert N. Butler Columbia Aging Center at Columbia University Mailman School of Public Health.
“The processes of life result in damage to the molecules inside our cells. Over time we believe that this damage accumulates, first affecting the cells, then the tissues that are made up of those cells, and eventually our organs, leading to the many diseases and declines that we associate with aging,” said Dr. Ryan.
Epigenetic clocks are based on a process called DNA methylation (DNAm) and allow researchers to predict and study the course of aging and aging end-points while an individual is still alive.
One approach to developing an epigenetic clock, called supervised machine learning, involves creating a statistical model from predictable epigenetic variation in tissue samples and then testing the model.
Once a clock is trained and tested, it can then help to study specific age-related outcomes. Some of the earliest clocks were devised to predict age itself, but over time, have evolved to quantify the pace of biological aging and mortality and the onset of disease.
HOW CAN WE USE EPIGENETIC CLOCKS?
Epigenetic clocks have proven to be powerful tools that can provide insights into age-related phenomena that arise in concert with predictable changes at the cellular level. For example, it turned out that epigenetic clocks trained to predict chronological age were useful for studying biological age.
WHEN A PERSON’S CHRONOLOGICAL AGE DID NOT CORRESPOND WITH THEIR PREDICTED BIOLOGICAL AGE, IT SUGGESTED THAT THEY WERE AGING FASTER THAN EXPECTED AND MIGHT BE AT HIGHER RISK FOR SOME DISEASES OF AGING.
Soon, researchers realized that predicting chronological age wasn’t the right goal and started using the same molecular markers and statistical tools to predict morbidity and mortality, even before clinical outcomes manifested. This allowed researchers to predict people’s biological age and potential health outcomes without extensive follow-up of participants.
In a review of epigenetic clocks published in American Journal of Human Biology in 2020, Dr. Ryan described nearly a dozen well-researched epigenetic clocks that can predict a wide range of diseases and risk factors at the population level, like cardiovascular disease, Type 2 diabetes, and chronic obstructive pulmonary disease (COPD) with a high level of accuracy.
Newer epigenetic clocks are looking at capturing variations in susceptibility to the effects of lifestyle factors to show, for instance, whether being sedentary will take a larger toll on predicted age for some groups versus others.
“One of the most surprising things about these clocks is that blood-based measures can tell us about biological aging in organs all over the body,” explained Dr. Ryan. To reflect aging in different organ systems more effectively from blood, a new Systems Age clock has been developed at Yale University.
DNAm can be analyzed from previously stored samples (e.g., dried blood spots), which allows scientists to re-examine previous studies, collect and bank samples for future use, and even pool data with new information to advance our understanding of aging.
For example, a recent study published in JAMA Network Open in 2024 examined DNAm from blood samples collected from cohorts of participants as part of the Framingham Heart Study. The Framingham Heart Study is an ongoing cohort study that has followed generations of participants, with enrollment of the first group beginning in 1948.
Dr. Ryan was part of this research team interested in looking at educational mobility between generations – the educational attainment of parents versus their offspring. Results showed that participants who were more educated than their parents tended to have a slower pace of aging as measured by the DunedinPACE epigenetic clock and lower mortality risk.
Epigenetic clocks can also be used as surrogate predictors to answer new questions as our knowledge advances.
We now have a tool that can go back through older data sets and be used to predict new measures.
“If there was a study carried out five years ago when we didn’t have a particular clock, or we did not measure something we’re interested in, we might be able to use these methods to go back and estimate that clock or a surrogate measure without collecting new data. That vastly increases our ability to do science and answer cutting-edge questions,” Dr. Ryan added.
STUDYING SEX DIFFERENCES USING EPIGENETIC CLOCKS
Epigenetic clocks provide insights into sex differences in lifespan. Between childhood and adolescence, male tissues begin to age at a different rate and show significantly advanced epigenetic age versus female tissues by early adulthood. This is consistent with males typically having a shorter lifespan versus females.
In an innovative study that included pairs of male-female fraternal twins, researchers from the Gerontology Research Center at the University of Jyväskylä in Finland found that male twins had faster epigenetic aging when compared to female twins, and differences were larger in an older group of twins compared to a younger group of twins.
Published in The Journals of Gerontology in 2022, Kankaanpää and colleagues found that sex differences were partially explained by larger body mass index and higher rates of smoking among males.
Authors suggested that differences in sex hormones (i.e., estrogen and testosterone) and their action on tissues may also contribute to differences in epigenetic age. Further research is needed to better understand the roles and mechanisms of sex hormones on epigenetic aging.
LIMITATIONS FOR EPIGENETIC CLOCKS IN PREVENTIVE HEALTH CARE
If epigenetic clocks have such wide-ranging predictive capabilities, why aren’t they used more often as a proxy measure for age and health risk, or used as a tool for preventive health care to motivate healthy habits?
First, epigenetic analyses are currently too expensive for many research studies and cost-prohibitive in public healthcare settings. Specialized instruments are required to examine genomes, quantify DNAm, and estimate epigenetic age.
These instruments are costly and technically challenging to use, which limits the number of research labs worldwide that do these types of analyses. Available approaches to derive and study DNAm, and methods to measure DNAm also require considerable staff time.
Dr. Ryan shared that his lab typically budgets US$250 - US$350 to analyze each sample. This means epigenetic testing for a typical study with 1,500 participants could cost around US$500,000!
Though there are efforts to develop clocks that run at a fraction of the price, we don’t yet know how such data could inform care in hospital and clinical settings or motivate individuals to adopt healthier habits.
Data from epigenetic clocks is most informative for population-level data and generally aligns with what is already known about lifestyle and environmental risk factors, particularly among middle-aged and older people. “We don’t yet know how far back we can go and still get accurate estimates of how epigenetic age predicts health outcomes and mortality later in life,” said Dr. Ryan.
Another consideration is that the socio-demographic diversity of samples used to develop epigenetic clocks is presently limited. Dr. Ryan explained, “Broadly speaking, we have the most data on middle-aged and older people, particularly white Americans and Europeans, and this population is where we’re best at predicting a range of outcomes.”
We don’t yet know whether existing algorithms used to predict aging outcomes equally applies for other age groups, like young adults, or for people living in other places and circumstances. In an article published in Environmental Epigenetics in 2023, Watkins and colleagues explained that because epigenetic clocks currently available have been derived from data with poor reporting of sociodemographic characteristics, this may introduce bias into the aging estimates and limit generalizability to diverse populations.
To illustrate, we have learned that sociodemographic factors like education and neighbourhood characteristics can affect DNAm via exposure to pollution or poor access to nutritious foods. It follows that epigenetic clocks calibrated to account for these characteristics may have better predictive capabilities.
THE BUSINESS OF EPIGENETIC TESTING
Epigenetic age testing entered the direct-to-consumer market only a few years ago, and today, more than a dozen companies offer these services. This process involves collecting your own samples (e.g., cheek swab, dried blood spot from a finger prick, or urine), sending it to a lab, and receiving tailored wellness reports with suggestions on what may help to slow down the aging process. The price of one-time testing ranges from about US$250 - US$500, and some companies even offer a monthly subscription so that you can have your estimated biological age tracked over time.
BEFORE YOU RUSH TO SIGN UP FOR EPIGENETIC TESTING, IT IS IMPORTANT TO CONSIDER THAT OUR KNOWLEDGE OF EPIGENETIC TESTING IS STILL RELATIVELY NEW, AND IT IS PRESENTLY BEST SUITED FOR STUDYING
INFORMATION AT A POPULATION LEVEL.
You’ll also need to consider whether having a report recommending healthy habits and avoiding unhealthy habits will motivate you to improve your lifestyle and sustain it over time. As a final thought, Dr. Ryan shared, “Epigenetic clocks are powerful tools that are changing how we study biological aging. But epigenetic age is just one piece of information in a constellation of other things and should be interpreted in the broader context of health measures.”