We Have Two Ages: Chronological and Biological Age—Why It Matters and How Epigenetic Age Is Measured

Professor David Sinclair, director of the Paul F. Glenn Center for Biology of Aging at Harvard Medical School, said, “Chronological age is not how old we really are; it is a superficial number. We all age biologically at different rates depending on our genes, what we eat, how much we exercise and which environmental toxins we encounter. Biological age determines our health and ultimately our lifespan. It is the number of candles we should really be blowing out. In the future, as our ability to control biological age advances, we may have fewer candles on our cake than the year before.”

Calculating Age Accurately

According to Professor Morgan Levine, a researcher who works on many different measures of aging in her laboratory, everyone has two ages: chronological age, the age on the calendar, and biological age, which essentially relates to the body's average level of fitness or health. Levine said, “People of the same chronological age do not have the same risk of cardiovascular disease, cancer or death.”

Levine and her team identified nine biomarkers measured in a simple blood test that appear to have the greatest effect on lifespan. These include blood sugar, kidney and liver measurements, and immune and inflammatory measures. Levine enters these numbers into a computer, and an algorithm does the rest.

Rather than simply measuring the passage of time, biological age aims to measure the aging of our bodily functions and even predict the risk of premature death. Many scientists and longevity advocates believe this information may not only help us understand our own aging process but also give us the power to change it.

People whose biological age is below their chronological age have a lower risk of death, whereas those who are biologically older have a higher risk and may be more prone to age-related diseases.

Perhaps the most important point is that, unlike results obtained from genetic tests, these findings can be changed. Doctors can use the information to advise patients to change their lifestyle, diet, exercise and sleep habits, taking steps to reduce risk and improve biological age.

Fascinated by aging since childhood, Levine even entered her own numbers into the algorithm. The results surprised her. “I have always considered myself a very healthy person. I am physically active and eat what I think is healthy, but my results were not as good as I hoped,” she said. She has now changed her diet and exercise routine and is trying to sleep more. Levine said, “It was a wake-up call.”

Startups Revealing How Old We Really Are

Jay Chan, a 30-year-old marine engineer, bought his mother a test kit from Elysium, a biotechnology and health supplement startup founded in New York in 2014, to measure her biological age using epigenetic analysis. It was a simple test requiring only a saliva sample.

Chan felt that knowing her biological age would benefit his 59-year-old mother, Ivy, because she was worried about aging. Chan told me, “She always talked about entering her 60s, how big a step it was and how it was the beginning of fading away.” Yet with her youthful appearance, she still felt healthy. “She looks 40!” he said.

They received the results about two months later: Ivy's biological age was 43.

Chan said, “It was a huge relief for her because it gives her new hope for planning her life. Knowing how quickly she is really aging gives her a renewed sense of self and how she should live over the next decade.”

The hope is that understanding biological age may lead to new life-extending interventions. The first step, however, is trying to measure it, which is far from easy. Researchers debate how to define it.

Determining Epigenetic Age

Horvath's “epigenetic clock” approach is considered by many scientists to be the gold standard for measuring biological age.

Epigenetics is the study of how your environment changes the way your genes work.

Horvath's clock analyzes DNA methylation, a process involving specific chemical changes in genetic material. In 2011, Horvath found that DNA methylation patterns could be used to predict human age accurately.

Horvath compared methylation to sand moving through an hourglass. “As we age, certain parts of DNA gain methylation and others lose it. There are literally millions of DNA sites that can be methylated,” he said. Horvath's clock tracks hundreds of these sites. The result was a formula capable of predicting age across the entire human lifespan, from fetus to old age.

Since then, Horvath and other scientists have developed more accurate clocks based on data collected from blood samples from the same group of people over decades. These data help clocks identify unhealthy aging more precisely and, as Horvath suggests, “predict time to death.”

In recent years, these methods have led to a boom in startups aiming to measure biological age for consumers. These tests are generally marketed as premium health products with sleek websites, minimalist packaging and influencer endorsements on social media.

The products vary in price and test format. Elysium's $499 saliva test is based on a biological clock developed by Dr. Morgan Levine, a former postdoctoral student of Horvath. The company's website states, “Breakthroughs in aging research are no longer a science-fiction myth but a scientific reality.”

A company called MyDNAge, claiming to offer “the most accurate and reliable DNA Age Test,” charges 299 dollars for a blood or urine test using a licensed version of Horvath's clock.

Popular but cheaper options do not use epigenetic clocks, such as Thorne's biological age test. It costs 99 dollars and requires a visit to a third-party laboratory to give a blood sample.

None of these tests has been approved by the FDA (United States Food and Drug Administration).

Horvath, who developed the epigenetic age measurement method, has mixed feelings about the tests' popularity. “At present, these clocks are not useful for the average person because we have no intervention to slow aging. Suppose a doctor orders an epigenetic clock test and it shows that a patient is older than they should be. What should the doctor say? Beyond repeating conventional health advice, there is no treatment they can prescribe. Could biological age become another stressful number on top of the many health indicators people already worry about, such as weight, blood pressure and daily steps?” he said. Horvath also emphasizes the danger of people misinterpreting their results.

Last year, he took the GrimAge test himself and found that his biological age was four years older than his chronological age. “I will not immediately conclude that I will live four fewer years. People are very complex, and things can change.”

For now, Horvath said consumers “should think of it more as entertainment.” “People are curious and want to boast to friends that they are younger, so why not?”

The summary of 50 years of epidemiological research is this: smoking has terrible health consequences. Obesity is just as bad; eat vegetables and exercise.

This is affirming information for people such as Ivy Chan who take epigenetic age tests from Elysium and similar companies.

Ivy Chan's son said, “Before the test, she exercised intermittently, but now she is more motivated to exercise regularly and eat healthily.”

Determining Biological Age by Measuring Telomeres

One approach focuses on the protective structures at the ends of our chromosomes that shorten when a chromosome replicates, known as telomeres. Their length therefore provides an approximate measure of biological aging.

Other approaches take blood samples and measure the presence of molecules associated with declining body function. Some approaches even scan people's eyes and claim to determine their risk of death.

Your Eyes May Reveal Your True Biological Age

On January 18, British Journal of Ophthalmology published a study in which Lisa-Zhuoting Zhu, a research fellow at the Centre for Eye Research Australia, said, “The retina is a window into a person's biological age. For example, if an individual's chronological age is 53 but their estimated retinal age based on retinal images is actually 60, our study showed that the gap between 60 and 53 years, a difference of 7 years, was associated with an increased risk of mortality,” she added.

Retinal analysis predicts mortality risk in older adults

Indeed, each 1-year increase in the retinal age gap was associated with a 2% increase in mortality risk from noncardiovascular and noncancer diseases, the authors reported.

The researchers said, “We found that the retinal age gap independently predicted mortality risk, particularly the risk of noncardiovascular/noncancer death.”

The authors explain that mortality data were available for a total of 35 thousand participants and were used to investigate the relationship between the retinal age gap and mortality. The study included approximately 11 thousand participants with an average age of 52.6. Among those analyzed, 51% were “fast agers” with a retinal age gap of more than 3 years, while nearly 28% had a retinal age gap of more than 5 years.

The researchers suggest that the noninvasive nature of fundus imaging (imaging the structures at the back of the eye) supports its development as a cost-effective screening tool that could help identify patients at increased mortality risk.

James Cole, an associate professor of neuroimaging at University College London, pointed out that although everyone ages, they do not all age at the same rate.

As Selami Şahin put it, “Eyes are the mirror of the heart; they do not know how to lie” :)