Basic Biology of Aging: Beyond Chronological Age: using a molecular clock for hidden biological aging
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Kit Curtius, PhD
Fred Hutchinson Cancer Research Center
Beyond Chronological Age: using a molecular clock for hidden biological aging
Biomarkers that drift differentially with age between normal and premalignant tissues, such as Barrett’s esophagus (BE), have the potential to improve the assessment of a patient’s cancer risk by providing quantitative information about how long a patient has lived with the precursor (i.e., dwell time). In the case of BE, such biomarkers would be particularly useful because esophageal adenocarcinoma (EAC) risk may change with BE dwell time and it is generally not known how long a patient has lived with BE when a patient is first diagnosed with this condition. In this study we first describe a statistical analysis of DNA methylation data derived from tissue samples from 50 BE patients to identify and validate a set of 67 CpG dinucleotides that undergo age-related methylomic drift. Our application of a Bayesian model to BE patients’ methylomic profiles exposes a wide heterogeneity in patient-specific BE onset times, with significantly earlier onsets occurring for familial BE patients. Our analysis supports the conjecture that differential methylomic drift occurs in BE (relative to normal squamous tissue) and hence allows quantitative estimation of the time that a BE. patient has lived with BE.
The Basic Biology of Aging seminar series is sponsored by The Nathan Shock Center of Excellence in the Basic Biology of Aging, the Genetic Approaches to Aging Training Grant, and the UW Healthy Aging and Longevity (HALo) Research Institute. The seminar features guest speakers presenting the latest research in the basic biology of aging.