What Is Biological Age and How Does It Differ from Real Age?

Biological Age Versus Chronological Age

Biological age is an estimate of accumulated cellular damage over time, whereas chronological age measures the calendar years since birth. Cleveland Clinic reports that scientists use that definition. Dr. Saadia Hussain, a family medicine provider at Cleveland Clinic, explains that chronological age is not as strong a predictor of health as people might think. Dr. Hussain states that biological age is a more accurate measure of how fast cells, tissues and organs are aging.

Cleveland Clinic notes that genes, habits and the physical environment affect biological age. Older biological age is linked to earlier development of chronic diseases. These conditions include cancer, dementia, Alzheimer's disease, diabetes and heart disease. The concept comes from a 1969 paper by British physician Alex Comfort. DNA methylation, an idea first published in 2013, is one of the most common markers used today.

Measurement approaches also rely on standard clinical tests. Algorithms combine measurements like blood pressure, blood sugar, cholesterol levels, heart rate, height and weight. However, these methods do not always align. In 2018, Belsky and colleagues evaluated 11 measures in 964 middle-aged participants and reported low agreement between different measures of biological aging.

How Biological Age Is Estimated

Researchers estimate biological age from DNA methylation patterns or blood biomarker panels, and wearables such as Garmin report a separate fitness age. Cleveland Clinic explains that small groups of chemicals called methyl compounds attach to the DNA in your cells. Methylation does not affect the DNA sequences. In 2013, Horvath published an epigenetic clock based on 8,000 samples across 82 datasets and 51 healthy tissues. A penalized regression model selected 353 CpG sites. The test-set median error was 3.6 years. This error means DNA methylation age differed from chronological age by less than 3.6 years in 50% of subjects.

Blood chemistry models offer an alternative approach. In 2018, Levine and colleagues built PhenoAge using 9,926 adults from the NHANES III dataset. Step one calculated phenotypic age from chronological age and nine clinical biomarkers. The nine markers are albumin, creatinine, serum glucose, C-reactive protein, lymphocyte percent, mean cell volume, red cell distribution width, alkaline phosphatase and white blood cell count. The biological age blood test guide reviews how these markers are evaluated. Step two regressed those values on blood DNA methylation to produce DNAm PhenoAge using 513 CpG sites. The authors reported that PhenoAge strongly outperforms previous measures for predicting all-cause mortality, cancers, healthspan, physical functioning and Alzheimer's disease.

Later epigenetic clocks changed the training targets. The PhenoAge authors noted that the first generation of epigenetic biomarkers used chronological age as a surrogate for biological age. In 2019, Lu and colleagues developed GrimAge. GrimAge combines seven DNA-methylation surrogates of plasma proteins with an estimate of smoking pack-years. The epigenetic clock guide details how these mathematical models work. In 2022, Belsky and colleagues introduced DunedinPACE. DunedinPACE tracked decline in 19 indicators of organ-system integrity across 20 years in the 1972-1973 Dunedin birth cohort. The authors distilled those changes into a single-time-point blood test scaled so that a value of 1 represents one year of biological aging per calendar year. The authors reported high test-retest reliability.

Wearable devices calculate a separate metric based on cardiovascular performance. According to Garmin, fitness age estimates your fitness compared to your actual age. Garmin states that fitness age is an interpretation of your VO2 max estimate compared to normal values for people of the same age and gender. Newer Garmin devices also factor in activity intensity, resting heart rate, and body fat percentage or body mass index. Garmin presents fitness age as a fitness score, separate from DNA-methylation and blood-marker estimates. The comparison of Whoop Age vs Garmin Fitness Age examines wearable metrics.

Is Biological Age Real and Accurate?

Different methods and repeat test runs give different biological age numbers for the same person. Cleveland Clinic states that biological age estimates are widely used in aging research but are not part of routine medical care yet. Online commercial tests take a blood or saliva sample and cost several hundred dollars. Dr. Hussain observes that it is not clear how reliable these tests are.

In 2018, Belsky and colleagues evaluated 11 biological aging measures in 964 middle-aged members of the Dunedin Study. The tested tools included telomere length, three epigenetic clocks, and three biomarker composites. The authors reported low agreement between different measures of biological aging. Epigenetic clocks correlated with one another, and biomarker algorithms correlated with one another. However, correlations between the clocks and biomarker algorithms were low. The authors concluded that the approaches may not measure the same aspects of aging. Effect sizes on physical outcomes were modest.

Repeat runs of the same test also disagree. In 2022, Higgins-Chen and colleagues reported that technical noise produces deviations up to 9 years between replicates for six prominent epigenetic clocks. The standard deviation of epigenetic age acceleration ranged between 3 and 5 years. The authors wrote that a change measured with a conventional clock after a lifestyle change "would be suspect." Retrained principal-component versions showed agreement between most replicates within 1.5 years. The paper discloses a company that licenses two authors' metrics and supplied some replicate data.

What Pushes Biological Age Up

Epidemiological studies identify body mass index, smoking history, male sex, and specific genetic variants as factors associated with accelerated biological age. A 2021 systematic review by Oblak and colleagues evaluated 156 publications. The authors found body mass index, HIV infection and male sex significantly associated with acceleration of one or more epigenetic clocks. The Horvath, Hannum, Levine and GrimAge clocks tended to agree in direction of effects, but varied in effect size.

Tissue-specific analysis shows differences in how body weight relates to cellular markers. In 2014, Horvath and colleagues evaluated blood, liver, muscle and adipose tissue. A correlation between body mass index and epigenetic age acceleration was observed only for liver tissue. Liver epigenetic age rose on average 3.3 years for each 10 body mass index units. The authors stated that this acceleration is not reversible in the short term after rapid weight loss induced by bariatric surgery.

Tobacco use is associated with higher readings on specific clocks. In 2022, Klopack and colleagues analyzed 2,978 adults over age 50 in the Health and Retirement Study. GrimAge was higher among participants with two smoking parents, individuals who smoked in youth, and adults with higher cigarette pack-years. PhenoAge and DunedinPoAm38 were also associated with pack-years. The authors noted that these findings suggest epigenetic aging is one mechanism linking smoking to disease and earlier death.

Genetic inheritance also influences biological aging rates. In 2013, Hannum and colleagues evaluated 656 individuals aged 19 to 101. The authors reported that the methylome aging rate is impacted by gender and genetic variants. In 2015, Marioni and colleagues estimated the heritability of the gap between chronological and epigenetic age at 0.43. Horvath also described a highly heritable measure of age acceleration in 2013.

What the Gap Between the Two Ages Means

The difference between biological age and chronological age correlates with chronic disease risk and mortality rates across large population groups. In 2015, Marioni and colleagues analyzed four cohorts of older adults. The authors reported that a 5-year higher difference between DNA methylation age and chronological age is associated with a 21% higher mortality risk after adjusting for age and sex. The risk remained 16% higher after adjusting for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease and APOE e4 gene status.

Broader multi-ethnic studies report similar group-level trends. In 2016, Chen and colleagues evaluated 13 cohorts encompassing 13,089 individuals across three racial or ethnic groups. The authors found that all considered measures of epigenetic age acceleration were predictive of mortality. These associations held independent of chronological age and after adjusting for additional risk factors. Cleveland Clinic notes that older biological age is linked to earlier development of cancer, dementia, diabetes and cardiovascular disease.

These figures represent statistical patterns across populations. They do not predict an individual's specific lifespan or date of death.

Can Biological Age Change?

Clinical trial data shows that calorie restriction can slow the pace of biological aging without significantly changing static biological age clock estimates. In 2023, Waziry and colleagues published a post hoc analysis of the CALERIE trial. The study randomized 220 adults without obesity to either 25% calorie restriction or an ad libitum diet for 2 years. Calorie restriction slowed the pace of aging as measured by the DunedinPACE algorithm. However, calorie restriction did not lead to significant changes in biological age estimates measured by DNAm clocks including PhenoAge and GrimAge. Treatment effect sizes were small, amounting to a 2% to 3% reduction in the pace of aging. The guide on how to lower biological age reviews lifestyle interventions tested in human trials.

Getting a Number for Yourself

Direct-to-consumer biological age testing is available through blood or saliva kits, though tests are not part of routine medical care. Cleveland Clinic notes that online commercial tests take a blood or saliva sample and cost several hundred dollars. Dr. Hussain emphasizes that it is not clear how reliable these tests are. The biological age test guide details testing options, sample methods and lab selection criteria. For standard blood panels, the biological age blood test resource details how nine standard biomarkers form the PhenoAge calculation. The metabolic age guide covers how metabolic age differs from biological age.

What Would Change This Answer

A measurement model that shows high agreement across different laboratories and repeatability within individuals would alter this assessment. Belsky and colleagues documented low agreement across 11 measures in 964 adults. Higgins-Chen and colleagues reported up to 9 years of run-to-run noise in conventional epigenetic clocks. Randomized controlled trials linking measured clock changes directly to improvements in clinical disease outcomes would also provide necessary evidence. In the 2-year CALERIE trial, calorie restriction produced only a 2% to 3% reduction in the pace of aging without a significant change in PhenoAge or GrimAge. The biological age test page compares test types if you want a number of your own.