Biomarkers for Biological Age Determination
The most clinically ready biomarkers for biological age determination are DNA methylation-based epigenetic clocks, mitochondrial function measures, and inflammatory markers (particularly IL-6), with DNA methylation clocks showing the strongest evidence for predicting mortality and multimorbidity. 1
Primary Biomarkers Ready for Implementation
DNA Methylation (Epigenetic Clocks)
- Epigenetic clocks are the most validated and accurate biological age biomarkers currently available, highly correlated with chronological age and predictive of mortality, functional decline, frailty, and brain aging 1
- DNA methylation profiles showing 3+ years beyond chronological age independently predict cancer mortality and overall mortality 1
- These measures are stable in stored biological samples and can be assessed from peripheral blood, making them practical for clinical use 1
- The technology is becoming increasingly cost-effective, though still relatively expensive compared to standard clinical tests 1
Inflammatory Markers
- IL-6 is the only known cross-sectional and longitudinal predictor of multimorbidity and one of the strongest predictors of incident mobility loss and disability 1
- Inflammation represents a central pillar of aging, as all hallmarks of aging directly or indirectly cause inflammatory states 1
- Higher inflammatory marker levels are associated with frailty, functional decline, cognitive decline, and death 1
- These markers are readily available in clinical laboratories and can be modified by interventions 1
Mitochondrial Function
- Mitochondrial function measures are ready for implementation based on multiple epidemiological studies 1
- These biomarkers reflect core cellular energy metabolism changes that occur with aging 1
Secondary Biomarkers with Emerging Evidence
Cellular Senescence Markers (p16INK4a)
- p16INK4a expression reflects cellular senescence and shows dramatic changes after cancer treatments, with breast cancer chemotherapy causing biological aging equivalent to 14-17 years in the first 12 months 1
- Anthracycline-based regimens cause significantly greater aging (23-26 years) compared to non-anthracycline regimens (9-11 years) 1
- High-throughput methods for measuring senescence in T lymphocytes, skin, and intramuscular fat are becoming available 1
- Currently not available in clinical laboratories, limiting immediate practical application 1
Autophagy Measures
- Autophagy measures are routinely used in mammalian studies and should be applicable to humans 1
- These biomarkers require further refinement before widespread clinical implementation 1
Biomarkers NOT Currently Recommended
Telomere Length
- Telomere length is NOT useful for measuring biological age at this stage due to excessive noise and wide longitudinal variations that cannot be explained by health events 1
- While telomere length has biological plausibility and tracks with chronological age, results have been inconsistent for survivorship outcomes 1
- New methods focusing on DNA damage response (marker of critical telomere shortening) may yield better results in the future 1
Important Clinical Considerations
Composite Approach
- No single measure represents an exhaustive assessment of biological aging; aggregate measures leveraging multiple biomarkers are needed 1
- The hallmarks of aging are interconnected, with failure of one mechanism leading to impairment in others 1
- Combining biomarkers with clinical history and geriatric assessments may provide the most comprehensive assessment 1
Key Limitations and Caveats
- Different manifestations of biological aging may occur on different time schedules, with some mechanisms preceding others 1
- Further research is needed before routine clinical implementation, including determining when knowledge of biological age would change treatment decisions 1
- Body composition markers also show promise but require additional validation 1
Practical Implementation
- For immediate clinical use, prioritize DNA methylation testing (if available and affordable) combined with IL-6 measurement 1
- In cancer patients specifically, consider p16INK4a expression if available, as it shows strong treatment-related changes 1
- Avoid relying on telomere length alone given current measurement limitations 1