Retroelement-Based Epigenetic Clock as a Biomarker of Biological Aging

Principal Investigator: 

Michael J. Corley, Assistant Professor of Immunology in Medicine

Lishomwa C. Ndhlovu, Professor of Immunology in Medicine

Background & Unmet Need

  • A person's biological age differs from their chronological age as it considers not just the passage of time but also factors such as genetics, lifestyle, nutrition, and comorbidities
  • Assessing biological age can serve as a more effective diagnostic tool for age-related diseases and as a prognostic tool for health screening
  • Epigenetic clocks are a way to determine biological age based on patterns of DNA methylation at specific regions of the human genome
  • However, existing epigenetic clocks face challenges related to accuracy, tissue specificity, biological relevance, and capturing diverse aspects of aging
  • Retroelements like HERVs and LINE-1 elements are kept silent by DNA methylation, but have been known to influence gene regulation, genomic stability, and disease upon reactivation with age
  • Unmet Need: Improved biomarkers of biological aging for assessing age-related risk and disease

Technology Overview

  • The Technology: Biomarker of biological aging based on the DNA methylation states of HERVs and LINE-1 retroelements
  • HERV-Age, LINE-1-Age, and a composite Retroelement-Age clocks were developed using data from >12 K individuals based on the DNA methylation states of HERV and/or LINE-1 elements
  • 100% of HERV-Age and 99.9% of LINE-1-Age methylation sites were unique and not part of existing epigenetic clocks*
  • PoC Data: All three epigenetic clocks were subsequently validated in >2 K samples, with high fidelity to chronological age
  • Retroelement-Age was able to measured the impact of therapeutic intervention, demonstrated by (i) a reduction in the biological age of samples from HIV patients undergoing retroviral treatment and (ii) human cortical organoids epigenetically rejuvenated through transient reprogramming

Technology Applications

  • Predicting the chronological age of humans and pan-mammalian species
  • Measure an individual's biological age more accurately to help predict risk of developing age-related diseases
  • Tool for monitoring the effectiveness of therapeutic interventions, such as antiretroviral and anti-aging treatments

Technology Advantages

  • Predicts chronological age with higher accuracy than existing models
  • Elucidates the association between DNA methylation of retroelements and human aging
  • Identifies potential biomarkers for anti-aging strategies

Diagram of workflow utilized to construct RetroelementAge and Retroelement-Age V2. B-E

Intellectual Property

Patents

  • PCT Application Filed WO2025043209A1: "Retroelement-age: biological aging captured by locus-specific human endogenous retroviruses and line-1 dna methylation states"

Cornell Reference

  • 10795

Contact Information

Jamie Brisbois, Ph.D.

For additional information please contact

Jamie Brisbois
Manager, Business Development and Licensing
Phone: (646) 962-7049
Email: jamie.brisbois@cornell.edu