Borderline Acceleration in Blood Epigenetic Age of Unclear Biological Importance in Knee Osteoarthritis Progression: Specimens and Data From the Osteoarthritis Initiative and Johnston County Osteoarthritis Project.

Details

• Alternative Title:
  Osteoarthritis and Cartilage, 2026, v. 34, no. 3: Borderline Acceleration in Blood Epigenetic Age of Unclear Biological Importance in Knee Osteoarthritis Progression: Specimens and Data From the Osteoarthritis Initiative and Johnston County Osteoarthritis Project.
• Journal Article:
  Osteoarthritis and Cartilage
• Personal Author:
  Brawner, Cindy Miranda ; Sturdy, Cassandra ; Arbeeva, Liubov ; Golightly, Yvonne M. ; Nelson, Amanda E. ; Jeffries, Matlock A.
• Description:
  Aging is a strong risk factor for osteoarthritis (OA). Previous studies have not found accelerated blood epigenetic aging in OA patients generally. The goal of this study was to evaluate peripheral blood epigenetic aging rates among OA patient subgroups.
  
  Genome-wide baseline blood DNA methylation data from the Osteoarthritis Initiative (n = 554) and Johnston County Osteoarthritis Project (n = 128) were generated using Illumina MethylationEPICv1 arrays on baseline samples of OA progressors (radiographic and/or pain progression in 2-5 years) vs. non-progressors. Epigenetic age was calculated using Horvath, GrimAge, PhenoAge, Horvath-IEAA, Hannum, Horvath-SkinBlood, and DunedinPACE calculators and epigenetic age acceleration was compared. Age-associated proteins were imputed using GrimAge and generalized logistic models developed to differentiate progressor groups.
  
  Borderline epigenetic age acceleration was found among radiographic progressors using the SkinBlood calculator (difference in epigenetic age acceleration, ΔEAA=1.5 years, q = 0.02), dual progressors (pain+radiographic) (ΔEAA = 1.2y, q = 0.05) and any progressor (pain+radiographic+dual) (ΔEAA = 1.1y, q = 0.02), although this was less than the reported error of the calculator (2.5 years). Radiographic progressors also exhibited accelerated epigenetic aging using the PhenoAge calculator (ΔEAA = 2.1y, q = 0.02). Imputed age protein-based models showed marginal performance for radiographic progression (area under the curve (AUC) = 0.63) and poor performance for other progressor types (pain AUC=0.54, dual AUC=0.52, any AUC = 0.57). Proteins chosen most frequently during modeling had prior links to OA (i.e., GDF8, MATN3, and interleukin 18).
  
  No meaningful difference in epigenetic age was seen among radiographic OA using 5 of 7 aging calculators, with minimal and likely not-clinically-relevant epigenetic age acceleration using the SkinBlood and PhenoAge calculators.
• Content Notes:
  Author manuscript
• Subjects:
  • Humans
  • Osteoarthritis, Knee
  • Disease Progression
  • Male
  • Female
  • Middle Aged
  • DNA Methylation
  • Aged
  • Epigenesis, Genetic
  • Aging
• Source:
  Osteoarthritis and Cartilage, 2026, v. 34, no. 3
• DOI:
  https://doi.org/10.1016/j.joca.2025.05.010
• ISSN:
  1063-4584 ; 1522-9653
• Pubmed ID:
  40480605
• Pubmed Central ID:
  PMC12354273
• Document Type:
  Text
• Funding:
  U01 DP006266/DP/NCCDPHP CDC HHSUnited States/ ; P60 AR030701/AR/NIAMS NIH HHSUnited States/ ; I01 BX004882/BX/BLRD VAUnited States/ ; R21 AR085344/AR/NIAMS NIH HHSUnited States/ ; U01 DP003206/DP/NCCDPHP CDC HHSUnited States/ ; R33 AR078075/AR/NIAMS NIH HHSUnited States/ ; I01 CX002494/CX/CSRD VAUnited States/ ; K08 AR070891/AR/NIAMS NIH HHSUnited States/ ; P60 AR049465/AR/NIAMS NIH HHSUnited States/ ; R61 AR078075/AR/NIAMS NIH HHSUnited States/ ; R01 AR076440/AR/NIAMS NIH HHSUnited States/ ; P60 AR064166/AR/NIAMS NIH HHSUnited States/ ; P30 AR072580/AR/NIAMS NIH HHSUnited States/ ; P20 GM125528/GM/NIGMS NIH HHSUnited States/
• Genre:
  Journal Article
• Place as Subject:
  North Carolina
• Pages in Document:
  372-379 (15 pdf pages)
• Volume:
  34
• Issue:
  3
• Download URL:
  https://stacks.cdc.gov/view/cdc/261353/cdc_261353_DS1.pdf
• File Type:
  [PDF - 688.46 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:7b64aad31272dee031d682a3797f5b744cb9b65b1e649991348303de7c562ef2708e0648e880f38303e05423b562f02d0d1c9d7275c44575595e168fe8ba98bf