PhenoAge Scientific Foundation

PhenoAge is designed to calculate an individual’s biological age based on various biometric inputs. It provides insights into a person’s health status by comparing their biological age to their chronological age. The algorithm is based on peer-reviewed scientific research by Dr. Morgan Levine and colleagues. It has been validated across diverse populations and is widely used in clinical research, population studies, and preventive medicine.
For practical use cases, read more about our PhenoAge Calculator. For API documentation and technical details, refer to the PhenoAge Calculator API. Or read about our entire Biometric Calculator suite.
Key Publications
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Levine, M. E. et al. (2018). “A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study.” PLOS Medicine, 15(12), e1002718. View Paper
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Levine, M. E. et al. (2019). “Correction: A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study.” PLOS Medicine, 16(2), e1002728. View Correction
Publication Summaries
Levine, M. E. et al. (2018). “A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study.” PhenoAge is a measure based on clinical biomarkers that estimates a person’s biological age in relation to their mortality risk, providing insight into their rate of aging. In this study, researchers assessed its usefulness across diverse populations using data from over 11,000 adults in the NHANES IV survey. PhenoAge was strongly associated with all-cause and cause-specific mortality, even after adjusting for chronological age, and was predictive across subgroups, including healthy individuals and the oldest-old. The findings support its potential as a clinical and research tool for identifying at-risk individuals and evaluating aging-related interventions, though more research in other cohorts is needed.
Levine, M. E. et al. (2019). “Correction: A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study.” A correction was issued for a study on the PhenoAge measure, which estimates biological aging and predicts health risks across diverse U.S. populations. The original article omitted a crucial step in the equation used to calculate PhenoAge, making it unsolvable as published. The corrected formula now includes the proper transformation of clinical variables, such as albumin, glucose, and white blood cell count, alongside chronological age. This clarification ensures accurate computation of PhenoAge for research and clinical applications in aging and mortality risk assessment.
Popular Adjustment
- Cramer, J. G. (2018). “New blood tests can reveal your life expectancy.” Age Reversal Forum. View Discussion
Adjustment Summary
Cramer, J. G. (2018). “New blood tests can reveal your life expectancy.” Although data for very old individuals is limited, the Levine data consistently falls below the expected linear trend, prompting further analysis. The author extracted points from Levine’s graph and used Mathematica to fit a correction formula that adjusts PhenoAge (P) to estimate DNAm PhenoAge (D) and a corresponding Mortality Score (MS). For example, using these corrections, an 84-year-old with a spreadsheet-calculated PhenoAge of 79.73 gets a DNAm PhenoAge estimate of 76.86 and a Mortality Score reduced from 0.498 to 0.413. These results are approximate and should be interpreted cautiously.
Required Biomarkers
PhenoAge requires the following clinical biomarkers for calculation:
- Age (chronological age in years)
- Albumin (g/dL)
- Alkaline Phosphatase (ALP) (U/L)
- Creatinine (mg/dL)
- C-Reactive Protein (CRP) (mg/L)
- Glucose (mg/dL)
- Lymphocyte Percentage (%)
- Mean Corpuscular Volume (MCV) (fL)
- Red Blood Cell Distribution Width (RDW) (%)
- White Blood Cell Count (WBC) (K/μL)
All biomarkers are required for accurate PhenoAge calculation. CRP values are log-transformed during the calculation process.
Algorithm Overview
PhenoAge uses a Cox proportional hazards regression model to predict mortality risk based on clinical biomarkers. The algorithm:
- Converts biomarkers to standardized units
- Applies weighted coefficients to each biomarker
- Calculates a mortality score using the weighted sum
- Converts the mortality score to biological age using a mathematical transformation
- Applies an adjustment formula to correct for age-related bias
The final result provides both the raw PhenoAge and an adjusted version that accounts for age-related systematic errors.
Validation and Limitations
PhenoAge has been validated in multiple studies:
- NHANES IV cohort: 11,000+ adults with mortality follow-up
- Diverse populations: Validated across different ethnicities and age groups
- Clinical outcomes: Predicts all-cause and cause-specific mortality
Current Limitations:
- Limited data for very old individuals (>85 years)
- May not capture all aspects of biological aging
- Requires standardized laboratory measurements
- Results should be interpreted in clinical context
The algorithm performs best in middle-aged to older adults and should be used alongside other clinical assessments.
Technical Implementation
Our PhenoAge implementation includes:
- Two-step calculation: Raw PhenoAge and adjusted PhenoAge
- Log transformation: CRP values are log-transformed before weighting
- Age adjustment: Correction formula reduces age-related bias
- Validation checks: Negative biological ages are rejected
- Legacy support: Accepts both standard and legacy parameter names
The algorithm returns both PhenoAge1 and PhenoAge2 variants, with the adjusted PhenoAge2 being the recommended final result.
Usage Guidelines
When to use PhenoAge:
- Adults aged 20-85 years
- Standard clinical laboratory results available
- Assessment of biological aging and mortality risk
- Research studies of aging interventions
Interpretation:
- PhenoAge < Chronological Age: Younger biological age
- PhenoAge > Chronological Age: Older biological age
- Difference: Years of accelerated or decelerated aging
Clinical Considerations:
- Results should be interpreted by healthcare professionals
- Consider alongside other clinical assessments
- Not a diagnostic tool for specific diseases
- May vary with acute illness or inflammation