Philemon Domoyeri

Pain in people living with HIV (PWH) is associated with greater psychological distress, poor sleep quality, and functional limitations. Yet the interconnections among these relationships remain understudied. Our study examined whether (a) sleep quality mediates the relationship between pain and depressive symptoms, (b) depressive symptoms mediates the relationship between pain and functional limitations, and (c) pain is associated with functional limitations through a serial pathway. A cross-sectional secondary analysis of 261 PWH was conducted. Pain was assessed using the pain subscale from the Medical Outcomes Study HIV Health Survey; lower scores indicated worse pain. Participants also completed the Pittsburgh Sleep Quality Index, the Center for Epidemiologic Studies Depression scale, and the Lawton and Brody Instrumental Activity of Daily Living (IADL) scale. Mediation analysis was performed using age, race, and education as covariates. Sleep quality partially mediated the relationship between pain and depressive symptoms, accounting for approximately 42% of the total effect. Depressive symptoms partially mediated the association between pain and IADL impairments (22%), whereas the serial pathway through sleep and depressive symptoms explained 8.4% of pain's total effect on IADL impairments. Improving sleep quality and depressive symptoms may reduce the negative impacts of pain on everyday functioning.

Nonspecific chronic low back pain (NSCLBP) is associated with central sensitization, and both diet quality and epigenetic aging are proposed modifiable, mechanistic contributors to this process. We examined how dietary profiles and epigenetic aging affect central sensitization in NSCLBP. Participants completed dietary, epigenetic aging (DunedinPACE, GrimAge), and central sensitization indicators, including conditioned pain modulation (CPM), heat and mechanical temporal summation (TS), and pain sensitivity questionnaire (PSQ). Dietary profiles were derived from latent profile analysis of dietary inflammatory index components. Nested regression models examined how dietary profiles and epigenetic aging predict central sensitization, adjusting for age, sex, BMI, and race, followed by Benjamini-Hochberg’s false discovery rate correction. We included 200 adults with NSCLBP: mean age 44 years; 62% African American; 55% female; mean BMI 31.33 kg/m². Five tests remained significant after Benjamini-Hochberg correction. DunedinPACE acceleration increased PSQ (β = 2.936, raw p = .034, FDR p = .034), GrimAge acceleration decreased mechanical TS (β = -0.270, raw p = .008, FDR p = .016). Increased low pro-inflammatory diet increased CPM only after accounting for DunedinPACE (β = 49.788, SE = 15.433, raw p = .002, FDR p = .013) and GrimAge (β = 52.685, SE = 15.281, raw p = .001, FDR p = .013). Increased low pro-inflammatory diet decreased heat TS facilitation in the GrimAge-adjusted model (β = -22.028, SE = 8.270, raw p = .009, FDR p = .049). Diet and epigenetic aging jointly, rather than independently, shape central pain processing in NSCLBP, suggesting protective effects of healthier diets.

Age-related changes in neurotransmitter systems contribute to declines in cognitive, emotional, and motor function, yet the biological mechanisms linking these changes to aging are not completely understood. Epigenetic regulation offers a promising framework to bridge this gap. DNA methylation-based biomarkers of biological aging (i.e., epigenetic clocks) capture cumulative and dynamic aspects of biological aging that may reflect vulnerability in neural systems beyond chronological age. However, whether these indices track with the integrity of neurotransmitter systems has not been systematically examined. This scoping review synthesizes evidence across human studies to evaluate how epigenetic aging processes influence neurotransmitter gene regulation and system function across the lifespan. We included 109 studies spanning 2005–2026. GABAergic genes (GAD1, GABRA2) showed the most consistent and reproducible age-related promoter hypermethylation across the cortex, inversely correlated with mRNA expression and corroborated by MRS evidence of cortical GABA decline. Dopaminergic and serotonergic evidence during normative aging was sparse; most epigenetic data in these systems came from disease cohorts. Histone modifications converged on neurotransmission and synaptic-plasticity loci, predominantly in Alzheimer’s disease tissue. Subcortical and brainstem nuclei central to monoaminergic and cholinergic systems remain under-investigated for normative aging epigenetic processes. Environmental and social determinants, socioeconomic status, childhood adversity, and chronic stress, were consistently associated with accelerated peripheral epigenetic aging, but brain-specific data are scarce.

This secondary data analysis aimed to determine the nature of the relationship between obstructive sleep apnea (OSA) risk, biological age acceleration, and nonspecific chronic low back pain (CLBP). In total, 199 adults aged 18–82 years who filled both STOPBANG and pain questionnaires subsetted for secondary analysis. Based on the STOPBANG questionnaire, 104 had a low OSA risk and 95 had an intermediate or high OSA risk. Dunedin Pace of Aging Computed from the Epigenome (DunedinPACE), Horvath’s, Hannum’s, PhenoAge, and GrimAge clocks were used to determine biological age and pace of biological aging. Individuals with low OSA risk reported increased DunedinPACE compared to those with intermediate/high OSA risk ( p < 0.001). There was a significant correlation between the risk for OSA and biological age acceleration measured by PhenoAge as well as pace of biological aging ( p < 0.05). Mediation analysis detected indirect effects of OSA risk on chronic pain outcomes through the pace of biological aging. Targeted interventions addressing OSA risk offers a promising therapeutic strategy. This could be particularly valuable for aging populations where both accelerated biological aging and chronic pain conditions are prevalent, offering a more holistic approach to improving nonspecific chronic pain outcomes through quality of sleep and restfulness.