Epigenetic aging is associated with clinical and experimental pain in community-dwelling older adults

Abstract

Gerontological research reveals considerable interindividual variability in aging phenotypes, which has motivated research efforts to identify “aging biomarkers.” Aging biomarkers are used to calculate biological age, which are better predictors of disease risk and residual lifespan when compared to chronological age alone. Emerging evidence using the epigenetic clock as an aging biomarker supports highly reliable individualized predictions about future health. This study aimed to determine whether an epigenetic aging biomarker was associated with chronic pain in older adults (60–83 years old). A subset of participants (n = 29) in the Neuromodulatory Examination of Pain and Mobility Across the Lifespan study underwent a blood draw, demographic, psychological, cognitive, and pain assessments. We estimated Horvath’s epigenetic clock and calculated the difference between epigenetic age and chronological age that has been previously reported to predict overall mortality risk. Older individuals without chronic pain (n = 9) had significantly “younger” epigenetic age compared to those with chronic pain (n = 20, p < 0.05). Older epigenetic age was associated with greater pain during daily activities (r = 0.494, p = 0.010) and anatomical pain sites (r = 0.741, p < 0.001) but not pain frequency/duration. An older epigenetic age was also associated with higher vibratory detection thresholds (r = 0.490, p = 0.021), heat pain thresholds (r = −0.478, p = 0.028), and pressure pain thresholds at the trapezius (r = −0.571, p = 0.006) but not thermal detection, pressure pain at the quadriceps or pain inhibition (p’s > 0.05). Epigenetic aging was associated with greater emotional stability (r = −0.461, p = 0.027), conscientiousness (r = −0.549, p = 0.007), and lower extraversion (r = 0.414, p = 0.049) but not depression or affect (p’s > 0.05). Epigenetic aging was also associated with lower episodic (r = −0.698, p = 0.001) and working memory (r = −0.760, p < 0.001). Our findings suggest that chronic pain is associated with accelerated epigenetic aging in healthy, community-dwelling older individuals, and future studies with larger samples are needed to confirm our findings. An aging biomarker such as the epigenetic clock may help identify people with chronic pain at greater risk of functional decline and poorer health outcomes.

Analysis of Epigenetic Age Predictors in Pain-Related Conditions

“…This result suggests that the association between biomarkers of biological age and painrelated conditions is not obvious and that it can be modulated by several factors, including, for example, the use of medications (64). Thus, the differences between our results and those reported by Cruz-Almeida et al (46) could be at least in part due to the different pain-related conditions evaluated. Furthermore, it should be noted that most of the subjects included in the FM and in the MOH/EM cohorts were younger than 60 years old, the lowest age in the cohort assessed by Cruz-Almeida et al The HPS study included a larger number of subjects older than 60 years, but also when we considered this subset of twins, no age acceleration was observed in high pain sensitivity subjects.…”

“…So far, only Cruz-Almeida et al investigated the association between Horvath's epigenetic clock and chronic pain (46). The authors reported higher epigenetic age acceleration, expressed as difference between DNAmAge and chronological age, among 20 participants (age range: 60-83 years old) with persistent painful symptoms during the past 3 months compared with healthy agematched controls.…”

“…To the best of our knowledge, only one study investigated epigenetic age acceleration in chronic pain (46). The authors analyzed 20 individuals with chronic pain between 60 and 83 years and 9 age-matched controls and evaluated biological age acceleration by calculating the difference between Horvath's DNAm age and chronological age.…”

Enrichment of genomic pathways based on differential DNA methylation profiles associated with chronic musculoskeletal pain in older adults: An exploratory study

“…Participants came to the laboratory multiple times for the NEPAL study, and previous findings have been reported elsewhere. 20 For the current exploratory investigation, pain assignment was performed during data analysis phase in a post hoc fashion. Participants were interviewed using a standardized pain history instrument regarding the presence of pain during the past three months across several body regions (i.e.…”

“…However, individuals reporting chronic pain had a significantly lower score on the 3MS compared to those without chronic pain (p ¼ 0.003). Details on this subset of participants have been previously reported by our group 20 and in Table 1. 2, and the full list is shown in Table S1.…”