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Longevity 101

How Is Biological Age Calculated?
The Main Methods and Which Are Worth Using

Aevum Protocol8 min read

There's no single test for biological age. Instead, scientists and clinicians use several methods, each capturing a different aspect of how the body is ageing. Some are simple and well validated. Phenotypic Age (PhenoAge) uses nine routine blood tests, such as glucose, creatinine, albumin and C-reactive protein, plus your age; in a study of more than 11,000 US adults, each additional year of PhenoAge was linked to a 9% higher risk of death. Simple physical tests are powerful too: in a study of nearly 140,000 adults in 17 countries, each 5 kg lower grip strength was linked to 16% higher mortality, and among older adults each 0.1 m/s faster walking speed was linked to 12% lower mortality. Other methods are more sophisticated but less ready for individual use. Epigenetic clocks, based on DNA methylation, predict health well in large studies but can vary between tests and laboratories. Telomere tests are of limited value for individuals, and organ age tests are still research tools. This article explains each method, how reliable it is, and which are most useful for you.

Key numbers

MethodKey finding
Phenotypic Age (9 blood markers; 11,432 US adults)Each extra year of PhenoAge: 9% higher risk of death
Grip strength (PURE study, 139,691 adults, 17 countries)Each 5 kg lower: 16% higher all-cause mortality; stronger predictor than systolic blood pressure
Walking speed (34,485 adults aged 65+)Each 0.1 m/s faster: 12% lower mortality
Cardiorespiratory fitness (122,007 people)Elite vs low fitness: 80% lower risk of death
Epigenetic clocksEarly clocks varied by up to 9 years on the same sample

The main methods

Overview, ways to estimate biological age: blood-based score (PhenoAge) well validated; grip, walking speed and fitness well validated; epigenetic clocks useful but variable; telomere length limited for individuals; organ age tests research only

1. Blood-based scores (Phenotypic Age). Phenotypic Age, developed by Morgan Levine and colleagues, combines nine routine blood tests (albumin, creatinine, glucose, C-reactive protein, lymphocyte percentage, mean cell volume, red cell distribution width, alkaline phosphatase and white blood cell count) with chronological age. It reflects liver, kidney, metabolic, immune and inflammatory health.

2. Physical function tests. Grip strength, walking speed, chair-stand tests, balance and cardiorespiratory fitness (VO2 max or treadmill tests) measure how well your body actually performs. They're inexpensive and directly linked to independence.

3. Epigenetic clocks. These estimate age from DNA methylation patterns in a blood or saliva sample. Second-generation clocks such as GrimAge and third-generation clocks such as DunedinPACE predict health outcomes better than the first clocks (see Epigenetic Clocks Explained).

4. Telomere length. The protective caps on chromosomes shorten with age, but telomere length varies greatly between people and is a weak guide for individuals (see Telomeres and Ageing).

5. Organ age tests. New tests use thousands of blood proteins to estimate the age of individual organs (see Organ Ageing Clocks).

Evidence strength

Strong: Phenotypic Age is well validated and uses routine tests. Phenotypic Age was developed in nearly 10,000 people in the US NHANES III survey and tested in 11,432 adults aged 20-84 in NHANES IV. Each additional year of PhenoAge was associated with a 9% higher risk of death overall (14% in adults aged 20-39), and it predicted deaths from heart disease, cancer, chronic lung disease and diabetes. Because it uses standard blood tests, it's affordable and repeatable.

Diagram, Phenotypic Age: biological age from routine blood tests. Albumin, creatinine, glucose, C-reactive protein, lymphocytes, mean cell volume, red cell distribution width, alkaline phosphatase, white cell count and your age; 9% higher risk of death for each extra year of Phenotypic Age (Liu et al., PLOS Medicine, 2018, 11,432 US adults)

Strong: physical function predicts survival.

Stat tiles, simple tests, powerful predictors: 16% higher mortality for each 5 kg lower grip strength, 12% lower mortality for each 0.1 m/s faster walking speed, and 80% lower risk of death with elite vs low fitness (PURE study, Lancet, 2015; Studenski et al., JAMA, 2011; Mandsager et al., JAMA Netw Open, 2018)

Moderate: epigenetic clocks are powerful but variable. Epigenetic clocks predict disease and death in large studies, and some, such as DunedinPACE, have high test-retest reliability. But early clocks gave results up to 9 years apart on the same sample, results differ between laboratories and sample types, and scores can rise temporarily during illness or stress (see Can You Reverse Your Biological Age?).

Limited: telomere and organ age tests. Telomere length is linked to ageing in populations, but its value for individuals is limited, and longer telomeres raise some cancer risks. Organ age tests are promising but not yet validated for routine clinical use (see Longevity Testing).

Important limitations.

Recommendations by situation

SituationWhat the evidence supports
Want an affordable biological age estimatePhenotypic Age from routine blood tests
Want to know your physical ageingGrip strength, walking speed, chair stands and a fitness test
Considering an epigenetic age testOptional; choose a named, validated clock and repeat with the same test
Offered a telomere testLimited value for individuals
Offered an organ age testResearch tool for now
Tracking progressRepeat the same measures every 6-12 months and look at trends

Practical notes

The most useful biological age measures are often the simplest: routine blood tests combined into a score such as Phenotypic Age, and physical tests such as grip strength, walking speed and fitness. They're inexpensive, repeatable and closely linked to health outcomes, and they point to clear actions such as strength training, aerobic exercise and managing blood sugar and inflammation. More advanced tests, such as epigenetic clocks, can add interest but should be interpreted with care (see Biological Age vs Chronological Age). Our Longevity Doctors use a combination of validated measures to estimate your biological age and track it over time, starting with the free longevity assessment.

References
  1. Levine ME, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging, 2018;10(4):573-591.
  2. Liu Z, et al. A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: a cohort study. PLOS Medicine, 2018;15(12):e1002718.
  3. Leong DP, et al. Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study. The Lancet, 2015;386(9990):266-273.
  4. Studenski S, et al. Gait speed and survival in older adults. JAMA, 2011;305(1):50-58.
  5. Mandsager K, et al. Association of cardiorespiratory fitness with long-term mortality among adults undergoing exercise treadmill testing. JAMA Network Open, 2018;1(6):e183605.
  6. Higgins-Chen AT, et al. A computational solution for bolstering reliability of epigenetic clocks. Nature Aging, 2022;2(7):644-661.

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