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Epigenetic processes and biological senescence in humans

$169,995FY2023SBENSF

Vanderbilt University Medical Center, Nashville TN

Investigators

Abstract

The rate of biological aging varies across individuals, being influenced by both genetic and environmental factors. This variation presents challenges in anthropological research and forensic practice for determining how old an individual was when they died based on skeletal measures of aging and frailty. This project leverages epigenetic and imaging data from living and postmortem clinical cohorts to examine the relationship between gene methylation and skeletal frailty and advance methods for understanding patterns of human senescence in the past and present. The results of this research are shared with the general public at the Boston Museum of Science, the Maxwell Museum in Albuquerque, NM, and at the Warren Anatomical Museum at Harvard University. The project supports student science education and training opportunities from elementary school to the postgraduate level (medical and graduate students). Outreach to groups underrepresented or underserved in STEM is planned at the Boston Museum of Science through its events for girls interested in STEM and through the Maxwell Museum’s educational programs. Using advanced imaging methods and epigenetic analysis, this project takes a novel, interdisciplinary approach to further characterize relationships among age, sex, and bone quality/quantity, especially in bone acquired in postmortem contexts. The investigators: (1) provide a methodological proof-of-concept demonstrating that epigenetic modification of genes in DNA derived from both femoral bone and blood samples in osteoporotic living patients is similarly observed in femoral bone and dental samples from skeletal remains, (2) identify any differences in epigenetic modification of the above genes in men and in women; (3) explore using tooth samples instead of femoral neck samples for assessment of methylation data that can provide information about skeletal health and age; (4) examine the utility of DNA methylation for the assessment of chronological age, using bone and dental samples, and (5) determine whether assessments of skeletal frailty and chronological age can be made based on imaging findings, thereby reducing the need for destructive sampling. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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