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Gerontological research reveals considerable interindividual variability in aging phenotypes, and emerging evidence suggests that high impact chronic pain may be associated with various accelerated biological aging processes. In particular, epigenetic aging is a robust predictor of health-span and disability compared to chronological age alone. The current study aimed to determine whether several epigenetic aging biomarkers were associated with high impact chronic pain in middle to older age adults (44–78 years old). Participants (n = 213) underwent a blood draw, demographic, psychosocial, pain and functional assessments. We estimated five epigenetic clocks and calculated the difference between epigenetic age and chronological age, which has been previously reported to predict overall mortality risk, as well as included additional derived variables of epigenetic age previously associated with pain. There were significant differences across Pain Impact groups in three out of the five epigenetic clocks examined (DNAmAge, DNAmPhenoAge and DNAmGrimAge), indicating that pain-related disability during the past 6 months was associated with markers of epigenetic aging. Only DNAmPhenoAge and DNAmGrimAge were associated with higher knee pain intensity during the past 48 h. Finally, pain catastrophizing, depressive symptomatology and more neuropathic pain symptoms were significantly associated with an older epigenome in only one of the five epigenetic clocks (i.e. DNAmGrimAge) after correcting for multiple comparisons (corrected p 's < 0.05). Given the scant literature in relation to epigenetic aging and the complex experience of pain, additional research is needed to understand whether epigenetic aging may help identify people with chronic pain at greater risk of functional decline and poorer health outcomes. [ABSTRACT FROM AUTHOR]

Our study aimed to identify differentially methylated CpGs/regions and their enriched genomic pathways associated with underlying chronic musculoskeletal pain in older individuals. We recruited cognitively healthy older adults with (n = 20) and without (n = 9) self-reported musculoskeletal pain and collected DNA from peripheral blood that was analyzed using MethylationEPIC arrays. We identified 31,739 hypermethylated CpG and 10,811 hypomethylated CpG probes (p s ≤ 0.05). All CpG probes were clustered into 5966 regions, among which 600 regions were differentially methylated at p ≤ 0.05 level, including 294 hypermethylated regions and 306 hypomethylated regions (differentially methylated regions). Ingenuity pathway enrichment analysis revealed that the pain-related differentially methylated regions were enriched across multiple pathways. The top 10 canonical pathways were linked to cellular signaling processes related to immune responses (i.e. antigen presentation, programed cell death 1 receptor/PD-1 ligand 1, interleukin-4, OX40 signaling, T cell exhaustion, and apoptosis) and gamma-aminobutyric acid receptor signaling. Further, Weighted Gene Correlation Network Analysis revealed a comethylation network module in the pain group that was not preserved in the control group, where the hub gene was the cyclic adenosine monophosphate-dependent transcription factor ATF-2. Our preliminary findings provide new epigenetic insights into the role of aberrant immune signaling in musculoskeletal pain in older adults while further supporting involvement of dysfunctional GABAergic signaling mechanisms in chronic pain. Our findings need to be urgently replicated in larger cohorts as they may serve as a basis for developing and targeting future interventions. [ABSTRACT FROM AUTHOR]

Our study aimed to identify differentially methylated CpGs/regions and their enriched genomic pathways associated with underlying chronic musculoskeletal pain in older individuals. We recruited cognitively healthy older adults with (n=20) and without (n=9) self-reported musculoskeletal pain and collected DNA from peripheral blood that was analyzed using MethylationEPIC arrays. We identified 31,739 hypermethylated CpG and 10,811 hypomethylated CpG probes (ps ≤ 0.05). All CpG probes were clustered into 5966 regions, among which 600 regions were differentially methylated at p ≤ 0.05 level, including 294 hypermethylated regions and 306 hypomethylated regions (differentially methylated regions). Ingenuity pathway enrichment analysis revealed that the pain-related differentially methylated regions were enriched across multiple pathways. The top 10 canonical pathways were linked to cellular signaling processes related to immune responses (i.e. antigen presentation, programed cell death 1 receptor/PD-1 ligand 1, interleukin-4, OX40 signaling, T cell exhaustion, and apoptosis) and gamma-aminobutyric acid receptor signaling. Further, Weighted Gene Correlation Network Analysis revealed a comethylation network module in the pain group that was not preserved in the control group, where the hub gene was the cyclic adenosine monophosphate-dependent transcription factor ATF-2. Our preliminary findings provide new epigenetic insights into the role of aberrant immune signaling in musculoskeletal pain in older adults while further supporting involvement of dysfunctional GABAergic signaling mechanisms in chronic pain. Our findings need to be urgently replicated in larger cohorts as they may serve as a basis for developing and targeting future interventions. [ABSTRACT FROM AUTHOR]

Our study aimed to identify differentially methylated CpGs/regions and their enriched genomic pathways associated with underlying chronic musculoskeletal pain in older individuals. We recruited cognitively healthy older adults with (n = 20) and without (n = 9) self-reported musculoskeletal pain and collected DNA from peripheral blood that was analyzed using MethylationEPIC arrays. We identified 31,739 hypermethylated CpG and 10,811 hypomethylated CpG probes (p s ≤ 0.05). All CpG probes were clustered into 5966 regions, among which 600 regions were differentially methylated at p ≤ 0.05 level, including 294 hypermethylated regions and 306 hypomethylated regions (differentially methylated regions). Ingenuity pathway enrichment analysis revealed that the pain-related differentially methylated regions were enriched across multiple pathways. The top 10 canonical pathways were linked to cellular signaling processes related to immune responses (i.e. antigen presentation, programed cell death 1 receptor/PD-1 ligand 1, interleukin-4, OX40 signaling, T cell exhaustion, and apoptosis) and gamma-aminobutyric acid receptor signaling. Further, Weighted Gene Correlation Network Analysis revealed a comethylation network module in the pain group that was not preserved in the control group, where the hub gene was the cyclic adenosine monophosphate-dependent transcription factor ATF-2. Our preliminary findings provide new epigenetic insights into the role of aberrant immune signaling in musculoskeletal pain in older adults while further supporting involvement of dysfunctional GABAergic signaling mechanisms in chronic pain. Our findings need to be urgently replicated in larger cohorts as they may serve as a basis for developing and targeting future interventions. [ABSTRACT FROM AUTHOR]

Our study aimed to identify differentially methylated CpGs/regions and their enriched genomic pathways associated with underlying chronic musculoskeletal pain in older individuals. We recruited cognitively healthy older adults with (n ¼ 20) and without (n ¼ 9) self-reported musculoskeletal pain and collected DNA from peripheral blood that was analyzed using Methylation EPIC arrays. We identified 31,739 hypermethylated CpG and 10,811 hypomethylated CpG probes (ps 0.05). All CpG probes were clustered into 5966 regions, among which 600 regions were differentially methylated at p 0.05 level, including 294 hypermethylated regions and 306 hypomethylated regions (differentially methylated regions). Ingenuity pathway enrichment analysis revealed that the pain-related differentially methylated regions were enriched across multiple pathways. The top 10 canonical pathways were linked to cellular signaling processes related to immune responses (i.e. antigen presentation, programed cell death 1 receptor/PD-1 ligand 1, interleukin-4, OX40 signaling, T cell exhaustion, and apoptosis) and gamma-aminobutyric acid receptor signaling. Further, Weighted Gene Correlation Network Analysis revealed a comethylation network module in the pain group that was not preserved in the control group, where the hub gene was the cyclic adenosine monophosphate-dependent transcription factor ATF-2. Our preliminary findings provide new epigenetic insights into the role of aberrant immune signaling in musculoskeletal pain in older adults while further supporting involvement of dysfunctional GABAergic signaling mechanisms in chronic pain. Our findings need to be urgently replicated in larger cohorts as they may serve as a basis for developing and targeting future interventions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]