Blood and Bone-Derived DNA Methylation Ages Predict Mortality After Geriatric Hip Fracture: A Pilot Study

Area of Science:

• Gerontology
• Molecular Biology
• Epigenetics

Background:

• DNA methylation patterns offer insights into biological aging.
• Bone tissue epigenetics in aging and mortality remain underexplored.
• Geriatric hip fracture patients represent a vulnerable population with high mortality.

Purpose of the Study:

• To analyze bone-derived DNA methylation for the first time.
• To compare DNA methylation clocks from bone versus whole blood.
• To correlate DNA methylation age with 1-year mortality in hip fracture patients.

Main Methods:

• Prospective enrollment of hip fracture patients (≥65 years).
• Collection of preoperative whole blood and intraoperative bone samples.
• Reduced representation bisulfite sequencing (RRBS) for DNA methylation analysis.
• Computational algorithms to establish methylation age in both tissues.
• Statistical analysis of age differences and correlations.

Main Results:

• Feasibility of DNA extraction and methylation analysis from bone samples.
• Strong correlation (R=0.81, p=0.0016) between bone and blood methylation ages.
• Significantly higher DNA methylation age (ΔAge) in non-survivors (mortality cohort) compared to survivors.
• Mortality cohort showed mean ΔAgeBone of 18.33 years and ΔAgeBlood of 16.93 years.

Conclusions:

• Bone-derived DNA methylation clocks are viable and correlate with blood-derived clocks.
• Elevated DNA methylation age is independently associated with 1-year mortality post-hip fracture.
• Targeting advanced DNA methylation may reduce mortality in this population.