Table 2 Summary of recommendations arising from the challenges of studying DNA methylation clocks in the context of aging

Challenges and recommendations

1. Delineation of the chronological and biological components of DNA methylation clocks

• Quantify the accuracy and robustness of “forensic” age estimates from different DNA sources

• Isolate pan-tissue “biological” aging changes for novel insights into aging

2. Functional characterization of tissue-specific and disease-specific clocks

• Refine tissue- and disease-specific clocks for disease-specific measures

• Deeper understanding of the pathogenesis of specific age-related diseases

• All published clock algorithms should be transparent and publicly available

3. Integration of epigenetics into large and diverse longitudinal population studies

• For predictive biomarkers of clinical utility

• Understand the cause and consequences of clock measures and any rate change on aging-related disease and longevity

4. Genome-wide analyses of aging and exploration of additional epigenomic marks

• Identity novel and potentially more sensitive chronological or disease-specific clock-like mechanisms

5. Single-cell analysis of aging changes and disease

• Explore functionality of clock-like and other aging-related epigenetic changes

• Define the components of tissue-specific changes

6. Generation of robust non-human data of aging

• Explore fundamental biology of aging using DNA methylation clocks in model organisms

• Expand and standardize the application of DNA methylation clocks to test longevity interventions in mice

7. Inclusion of epigenetics within current genetic ethical and legal frameworks

• To educate and protect the public from misinformation and misuse