High-Impact Pain and Epigenetic Aging: Findings from the Health and Retirement Study

High-impact chronic pain (i.e., pain that interferes with activities and function) is a leading cause of disability disproportionately affecting middle-aged and older adults in the United States. Epigenetic aging, a proxy of biological aging measured via DNA methylation (DNAm) clocks, may help provide valuable insights into mechanisms at the intersection of chronic pain and aging. We examined the association between pain impact and epigenetic aging in a nationally representative sample of U.S. adults ≥50 years old. Cross-sectional data from the 2016 Health and Retirement Study was used to evaluate associations between pain impact (no pain, low-impact pain, high-impact pain) and 13 first, second and third generation epigenetic clocks (Bocklandt, Garagnani, Horvath DNAmAge, Hannum, Weidner, Lin, Vidal-Bralo, Yang epiTOC, Zhang, PhenoAge, Skin&Blood, GrimAge, and DunedinPoAm). The sample consisted of 3,855 adults with data on pain impact, epigenetic clocks, and sampling weights. As compared to no pain controls (n=2,242, 59.8%), individuals reporting high-impact pain (n=1,023, 25.8%) showed accelerated epigenetic aging (Zhang, PhenoAge, GrimAge, and DunedinPoAm), adjusted for demographic and lifestyle factors (Bonferroni adjusted p’s<0.05). Additionally, individuals with high-impact pain showed accelerated GrimAge compared to low-impact pain. There were no significant differences in any of the 13 epigenetic clocks between individuals reporting low-impact pain and no pain controls. Our findings support accelerated epigenetic aging in middle-to-older-aged adults with high-impact chronic pain in the U.S. population. Further research is needed to assess the potentially bidirectional relationship between high-impact pain and biological aging processes across the lifespan. Funded by the National Institute on Aging (T32AG049673).