PROJECT SUMMARY Converging lines of evidence suggest that telomere biology plays a central role in the pathogenesis of cancer and cardiovascular disease, the two leading killers in the USA. Telomere length (TL) is heritable, but environmental exposures influence TL dynamics, i.e., TL and its age- dependent shortening. These findings bring into sharp focus the opportunities and challenges facing population-based telomere research. High throughput TL measurements and TL imputations from whole genome sequencing have opened up possibilities that once seemed unattainable in population research. However, questions have been raised regarding the indiscriminate reliance on such modalities and their shortcomings compared to labor-intensive techniques of TL measurements used in small populations and specialized clinical settings. RFA- AG-19-023 and a companion RFA-AG-022 have called for developing standards of TL measurements in epidemiological research. This U01 proposal responds to the first RFA. Its Aims are two-tiered: Aims 1 and 2 (the proposal’s first arm) will compare the abilities of two TL measurements (Southern blotting of the terminal restriction fragments and qPCR-based analysis) to capture elements of TL dynamics and TL-related outcomes in two longitudinal studies. Aims 3- 5 (the proposal’s second arm) address the standardization and collaborative protocols that meet the goals and central mission of the Telomere Research Network (TRN) established by RFA-AG- 19-023. If reliable TL measurements predicting disease can be identified or developed, they might become a component of the individual’s biogenetic health profile, envisioned to drive personalized medicine in the future.