Biological Age Tests

Setting Your Health Baseline: How Old Am I? Biological Age Tests

Biological age tests determine how old your physical body is, in contrast with your calendar age. They are necessary to set your health baseline so you can measure if treatments actually reverse aging.

“We are living in exciting times. Several treatments appear to reverse epigenetic aging.” — Dr. Steve Horvath, leading biological clockmaker

Biological Age Test History

Biological age testing is a young field, with the first epigenetic clock being created in 2009 by Axel Schumacher followed in 2013 by significant advancements to use multiple tissue samples by doctors Gregory Hannum and Steve Horvath. With first-generation DNA methylation-derived epigenetic clocks, it is possible to take cell samples, analyze them using these clocks, and accurately guess the donor’s calendar age within 3.6 years. 

Alternate methods to estimate chronological age using transcriptomic and proteomic data, saliva or telomere length, have proven less accurate as there are multiple challenges in biological age testing.

Biological Age Tests — Flaws and Limitations

Many biological age tests ask for your chronological age as part of their determination of your biological age. This should not be necessary and could influence your results if they use it in their formula to determine your biological age.

Current biological age tests report a single age result per person. In actuality, parts of our body are at different biological ages. For example, If a person has body parts which each measure out as biologically between 30 and 40 years old, yet has a brain which measures at 85, how biologically old are they?

Is it possible to create a credible test to estimate a person’s biological age (or age of each component) within one year?

For a comprehensive biological age test to be that accurate, it requires a wide range of data including:

1. Biological data from blood, stool, urine and saliva tests, collected over a sufficient range of conditions and time to account for daily fluctuations. Data analysis must include:
   • That typically covered during an advanced annual physical examination.
   • Whole genome genetic and epigenetic data and longevity biomarkers. These can include molecular, cellular, physiological and genetic markers associated with aging, such as telomere length, DNA methylation patterns, inflammatory markers, hormonal levels and oxidative stress markers.
   • Cancer screening.
   • Microbiome testing.
2. Digital data from whole body scans. (skeletal system, musculature, vasculature, organs, body fat percentage, etc.). 
3. Visual data on physical appearance. (Skin health, hair health, etc.)
4. Mental and psychological competency test results including testing your level of stress.
5. Physical capability test results (strength, speed, agility, endurance, stability, etc.) including monitoring data (blood pressure, heart rate, etc.)
6. Sensory system capability test results (vision, hearing, smell, taste, touch)
7. Calendar age at the time of all tests across multiple iterations to create a historical record.
8. A clear standard for what is the individual component biological age associated with various ranges from test data. For example, scores from X to Y in a test of Z indicate association with a gender of age ## for that body element. Top biohacker Brian Johnson’s personal measurement site provides an excellent template.
9. Large-scale diverse population data for all of the above matched to the associated biological age standard for each test.

Full comprehensive data and scientific agreement on #8 and #9 do not exist yet. #8 may change dynamically with human healthspan and lifespan increases. There is also no agreement on which biomarkers can be used for longevity clinical trials.

So given the known limitations and major flaws, are biological age tests worthwhile? Yes, if they influence making healthier lifestyle choices or lead to early discovery of treatable disease.

Biological Age Tests — How Fast Am I Aging?

According to Dr. Horvath, “Aging manifests in 30 year olds.” If you are fortunate enough to be just 30 years old, you should consider taking a biological age test to set your health baseline. If you are older, it still makes sense to establish a starting position, then test annually to see how you progress. 

Dr. Horvath’s latest technology includes PhenoAge and GrimAge from the non-profit Clock Foundation. GrimAge provides epigenetic clock testing for physicians and aging researchers for preclinical and clinical studies. It is considered the best estimation of all-cause mortality as the rate of change in GrimAge shows an increased hazard ratio for predicting death. If the rate of change moves up quickly, you are likely in trouble and should seek medical help.

GrimAge has received global scientific validation for accuracy in tracking age. As of 2019, GrimAge is 18% more accurate than calendar age and 14% better than previously-described epigenetic biomarkers. In predicting time to coronary heart disease, GrimAge is 61% more accurate than chronological age and 46% better than previously-reported epigenetic biomarkers. Also, GrimAge outperforms in predicting time to cancer and time to menopause. Of note, if patients are sick when taking the GrimAge test, it affects the results because blood health factors show the illness.

As of August, 2022, Dr. Horvath has created and tested GrimAge2 which is even more accurate as it factors in whether patients are smokers and biomarkers for Hemoglobin A1C and C-reactive protein. According to GrimAge2 predictive factors for increased longevity, it is very important to maintain high levels of vegetable intake, good levels of HDL cholesterol and healthy lung function.

Dr. Horvath has found that blood and buccal (cheek swab) cells are the best indicators for testing aging. For comparison, they are also testing animals such as cats, dogs and even elephants as part of 3rd-generation, pan-mammalian clocks.

Biological Age Tests — Available for You!

Unfortunately, GrimAge is not providing direct to consumer testing at this time.

Here are the published biological age test options, none of which are fully comprehensive in their data gathering and methodology:

Actual Age (free) by Longevity Playbook

• Created in 2023 by Dr. Michael Roizen, Chief Wellness Officer Emeritus of the Cleveland Clinic.
• 10-15 minute survey to answer questions about your health and lifestyle.
• Questions include: How old are you?, fasting blood sugar level, LDL level, blood pressure, resting heart rate. Know these before taking the test.
• Provides your “real age” along with food, exercise and stress reduction tips to improve your health. The tips are useful, but not fully personalized with your survey answers.
• Here’s an insight from one person who took this test, “It said my actual age is 66.  Real age 81. I think it got one of the two correct.”

AltumAge by Shift Bioscience (not publicly available)

• Neural network improves on prior linear regression epigenetic clocks for people older than 59 by factoring in dangerous conditions.
• Developed based on 142 publicly available data sets from several human tissues. Not designed for testing bloodwork.
• Predicts higher age acceleration for those prone to tumors, for cells that exhibit age-related changes in vitro, such as immune and mitochondrial dysfunction, and for samples from patients with multiple sclerosis, type 2 diabetes, and HIV, among other conditions.

AdaptAge (not publicly available)

• Framework for integrating causal knowledge into epigenetic clock models to adjust for beneficial age-related adaptive changes.
• Created in 2022 by a collaboration of genetics scientists including Steve Horvath and Vadim Gladyshev.

CausAge (not publicly available)

• Framework for integrating causal knowledge into epigenetic clock models to adjust for DamAge and AdaptAge changes.
• Performs epigenome-wide Mendelian Randomization on large-scale genetic datasets to identify CpG sites causal to aging-related traits.
• Created in 2022 by a collaboration of genetics scientists including Steve Horvath and Vadim Gladyshev.

ClockBase (Gladyshev Lab, not publicly available)

• A comprehensive platform for biological age profiling in human and mouse.
• Biological age estimates based on multiple aging clock models applied to more than 2,000 DNA methylation datasets and nearly 200,000 samples.

DamAge (not publicly available)

• Framework for integrating causal knowledge into epigenetic clock models to adjust for age-related damaging changes.
• DamAge acceleration is associated with various adverse conditions (e.g., mortality risk).
• DamAge is potentially reversable via cellular reprogramming.
• Created in 2022 by a collaboration of genetics scientists including Steve Horvath and Vadim Gladyshev.

Glycan Age ($348 for 1 test. $599 for 2.)

• At-home finger-prick blood test which is mailed back in.
• Glycans are sugar molecules that surround and modify proteins in your body. Glycan Age claims they respond to your lifestyle choices and indicate the inflammatory state of your immune system, which in turn determines your biological age.
• They believe measuring the amount of good and bad glycans can determine biological age.
• Good glycans decrease with age. Bad glycans increase.
• Their accuracy level is unclear. They are trying to benchmark against telomere lengths of a variety of cells.
• Their results have large variations (up to 38 years in one of their examples) against chronological age. They do not have mortality studies.
• Testing a single indicator (glycans) is unlikely to accurately reflect all aspects of biological aging.

iAge by Edifice Health (Not available to the general public yet. Expected in 1H, 2024)

• Founded by David Furman, PhD and Mark Davis, PhD.
• From a standard blood draw, Inflammatory Age^® predicts multi-morbidity and immune decline and provides actionable items to improving your immune health.
• iAge can be measured once to give a snapshot profile, or tracked over time to give a measurement of longitudinal changes of the effect of interventions.
• The algorithm was created from AI analysis of data from the 1000 Immunomes Project and the Framingham Heart Study.
• Based on the iAge^® test results, Edifice Health claims to have identified over 150 actionable interventions suggested to improve your iAge^® score. These include specific combinations of nutritional supplements, nutraceuticals, medical foods, prescription drugs, and life-style modification. David Furman is writing a book on actionable interventions.
• Since 2020, Edifice has received over $12MM in funding from early venture funds associated with Bayer and Human Longevity.

Index by Elysium ($499)

• At-home saliva-based epigenetic test kit developed by Professor Morgan Levine, Ph.D., at Yale School of Medicine and former employee in Horvath’s lab.
• Analysis of 100,000-150,000 biomarkers using an Illumina chip, an upgrade on her work creating PhenoAge (considered the second clock) in Dr. Horvath’s laboratory.
• Epigenetics involves changes in your biology caused by modifications in gene expression rather than the underlying genetic code itself. Factors that can influence your epigenetics include your diet, exercise habits, alcohol consumption, and stressors like sleepless nights.
• Provides biological age plus Cumulative Rate of Aging, the pace at which your body has aged for every year you’ve been alive.

InnerAge 2.0 from InsideTracker ($249, discounted if buying multiple tests)

• Tracks 13 biomarkers for women and 17 for men
• Combination of advanced bloodwork (blood test included) and lifestyle factors
• Provides results as Personalized optimal zones – Based on your age, gender, ethnicity, activity levels and goals. Indicates impact on your biological age from each marker.
• Offer premium “Ultimate” plan with 43 biomarkers for $659
• Offers a nutrition database with over 7,500 food items scientifically proven to improve specific biomarker levels. Additionally, receive advice on hundreds of supplements as well as lifestyle and exercise suggestions to help you reach your optimal zones.

Insilico Medicine (not publicly available)

• Researching the microbiome to determine age.
• Accuracy to within 6 years.
• Biological targeting platform PandaOmics focused on identifying anti-aging drug candidates.

Knowledge-based deep neural network clock (not publicly available)

• Transcriptomic clock using gene expression data to predict biological age.
• More accurate than RNAAgeClock.
• Findings suggest a link between transcriptomic aging and health disorders, including psychiatric traits.

Levine Phenotypic Age (free)

• A downloadable spreadsheet to enter 9 factors from blood work results
• Developed from studies on over 11,000 adults
• Calculates your phenotypic age and expected mortality

LifeLength — HealthTAV telomere length testing ($410)

• Blood test for short telomeres associated with many age-related illnesses and declining health.
• Telomere length is not accurate for predicting mortality.

myDNAge — Blood and urine tests ($299 each) based on the first generation version of the Horvath Clock

• Company is not affiliated with Dr. Horvath.
• Claims to be the Most Accurate Biological Clock, but provides no evidence.
• Target over 2,000 CpG sites, much fewer than competitors.
• Offer a Dog Age Test kit ($299), although free with other purchase.

PhotoAgeClock (not publicly available)

• Based on left and right eye photos of over 8000 people.
• Mean-Average Error rate within 2.3 years. Varies by age of participant.
• Not considered official because it doesn’t use cellular biomarkers. 

Real Age by ShareCare (free) online questionnaire and results

• Created in 1999 by Dr. Michael Roizen, Chief Wellness Officer of the Cleveland Clinic.
• Currently owned by Sharecare, a health and wellness platform.
• 15-20 minutes to answer questions about your health and lifestyle.
• 29 million people have taken it.
• Provides your “real age” and tips to improve your health.
• Of note, they still recommend daily aspirin. See Keep Health’s article for the risks.

RNAAgeCalc (not publicly available)

• Transcriptomic clock using gene expression data to predict biological age.
• Less accurate than knowledge-based deep neural network clock.
• Findings suggest a link between transcriptomic aging and health disorders, including psychiatric traits.

TallyAge from Tally Health ($229 per age test or $129-$199 for various levels of monthly health membership services including age testing)

• Founded by David Sinclair and led by CEO Melanie Goldey.
• Epigenetic aging clock based on DNA methylation analysis, analyzing around 850,000 DNA methylation sites for biomarkers of healthy aging.
• Using a proprietary machine learning model, this data is used to determine a person’s TallyAge, which may be younger or older than their chronological age.
• 8,000 diverse beta testers to establish initial result metrics.
• Provide personalized insights, lifestyle recommendations and longevity supplements designed to help lower your TallyAge.
• Competitor TruDiagnostic penned an insightful Open Letter questioning some of TallyAge’s methodology.

TruDiagnostic ($229.99 for TruAge PACE and $499 for TruAge Complete Collection)

• Used by 16+ anti-aging clinical trials including from Harvard, Cornell and OneSkin.
• Blood test using methylation testing.
• Receive suite of comprehensive epigenetic reports.
• Raw data available for personal download
• Here’s how their lab works.

Tru Me Labs (TruAge $110)

• At-home mail-in DNA-based saliva epigenetic test kit.
• Use methylation on only a tiny fraction of the billions of nucleotides in your DNA. Claim an unproven statistical error of approximately 4.75 years.
• Only provides your calculated biological age as a result. Lack rigor and transparency in their methodology.
• Results can show huge and unlikely differences in chronological vs biological ages.

Young.ai (free) iPhone app from Hong Kong–based Deep Longevity and Dr. Polina Mamoshina

• Tracks multiple biological clocks, using biomarkers that show the rate of aging at the molecular, cellular, tissue, organ, and system level. 
• Users upload their data from photos, surveys, biological samples, and activity trackers into an AI system which provides a personalized to-do list to promote healthier aging.
• Believe their AI method will be more powerful than Horvath’s models for detecting aging.
• 5 most important predictors; (Albumen) liver function, metabolic function (glucose), urea (renal), erythrocytes (respiratory), hemoglobin. (Side note: Dr. Horvath — agrees with Dr. Polina on these targets.) Facial features, microbial taxa can be factored in too.
• Smoking under the age of 40 has much more impact on human aging than after that.
• Accuracy between 6-7 years. Expected to improve rapidly with more datasets.

Best Articles Comparing Biological Age Tests

The following authors have written good articles on their experiences using some of the above biological age tests.

• What’s My Age Again? Reviewing Three Online Biological Age Testing Tools — Nick Engerer  (Levine, Aging.AI, Real Age)
• The DNA Test That Tells You Your “Real” Age (Index by Elysium)
• InsideTracker InnerAge Review from InnerBody Research. Includes 25% discount code.

Anti-Aging Clinical Trials

The following clinical trials are using biological clocks to measure the impact on aging.

TRIIM by Greg Fahy and Robert Brooke

• Phase 1 initial study on 9 male humans showed a 2.5 year reduction in GrimAge using a cocktail of thymus gland treatment drugs.
• Phase 2 TRIIM-X indicated it would have 85 participants and conclude in November, 2022. However, as of August 2022, only 20 men and 6 women have enrolled in TRIIM-X. The study uses multiple agents in combination with personalized doses of recombinant human growth hormone (somatropin), metformin, and DHEA. Both trials have had participant issues with finger stiffness, carpal tunnel syndrome, arthralgias and prostate-specific antigen spikes in about 1/3 of participants. Many participants have reported significant improvements in their health and enjoyment of life.

Nicotinamide Riboside (NR) in Hospitalized Patients (2019)

• Investigating the potential benefits of 90 days of NR supplementation on recovery time and mortality using GrimAge.
• Preliminary results were achieved in December 2021 and End of Study results will be reported after December 2022.
• For more on the benefits and safety profile, see Keep Health’s NR article.

Also, multiple researchers are working on a CellAgeClock to track aging in single in-vitro cells for the purpose of testing new anti-aging drugs. 

Databases of Genes which Impact Aging

For the curious, here are two public databases maintaining the known list of genes which impact aging. 

GenAge — database of genes which impact aging

SynergyAge — a curated database to examine the combination of multiple genes on lifespan, seeking to identify synergistic and antagonistic interactions of longevity- associated genes via BioRxiv.org (BioArchive). Run by Gabriela Bunu, PHD student at the Romanian Academy. 

Conclusion

This concludes our article comparing biological age tests. As your reward for reading and to satisfy your curiosity, we recommend you go try Actual Age for free, then consider InnerAge or TruDiagnostic as well. Alternatively, pursue the title of best biohacker and create your equivalent of Brian Johnson’s personal measurement site.