Food insecurity is associated with chronic pain and high-impact chronic pain in the USA.

OBJECTIVE: This study evaluated whether food insecurity (US Adult Food Security Survey) was associated with chronic pain (≥ 3 months) and high-impact chronic pain (i.e. pain that limits work and life) among US adults. DESIGN: Cross-sectional analysis. SETTING: Nationally representative sample of non-institutionalised adults in the USA. PARTICIPANTS: 79 686 adults from the National Health Interview Survey (2019-2021). RESULTS: Marginal, low and very low food security were associated with increased prevalence odds of chronic pain (OR: 1·58 (95 % CI 1·44, 1·72), 2·28 (95 % CI 2·06, 2·52) and 3·37 (95 % CI 3·01, 3·78), respectively) and high-impact chronic pain (OR: 1·28 (95 % CI 1·14, 1·42), 1·55 (95 % CI 1·37, 1·75) and 1·90 (95 % CI 1·65, 2·18), respectively) in a dose-response fashion (P-trend < 0·0001 for both), adjusted for sociodemographic, socio-economic and clinically relevant factors. Participation in Supplemental Nutrition Assistance Program (SNAP) and age modified the association between food insecurity and chronic pain. CONCLUSIONS: These findings illustrate the impact of socio-economic factors on chronic pain and suggest that food insecurity may be a social determinant of chronic pain. Further research is needed to better understand the complex relationship between food insecurity and chronic pain and to identify targets for interventions. Moreover, the consideration of food insecurity in the clinical assessment of pain and pain-related conditions among socio-economically disadvantaged adults may be warranted.

Self-reported pain and fatigue are associated with physical and cognitive function in middle to older-aged adults.

Persistent fatigue is often reported in those with chronic musculoskeletal pain. Separately, both chronic pain and chronic fatigue contribute to physical and cognitive decline in older adults. Concurrent pain and fatigue symptoms may increase disability and diminish quality of life, though little data exist to show this. The purpose of this study was to examine associations between self-reported pain and fatigue, both independently and combined, with cognitive and physical function in middle-older-aged adults with chronic knee pain. Using a cross-sectional study design participants (n = 206, age 58.0 ± 8.3) completed questionnaires on pain and fatigue, a physical performance battery to assess physical function, and the Montreal Cognitive Assessment. Hierarchical regressions and moderation analyses were used to assess the relationship between the variables of interest. Pain and fatigue both predicted physical function (ß = -0.305, p < 0.001; ß = -0.219, p = 0.003, respectively), however only pain significantly predicted cognitive function (ß = -0.295, p <0.001). A centered pain*fatigue interaction was a significant predictor of both cognitive function (ß = -0.137, p = 0.049) and physical function (ß = -0.146, p = 0.048). These findings indicate that self-reported fatigue may contribute primarily to decline in physical function among individuals with chronic pain, and less so to decline in cognitive function. Future studies should examine the impact of both cognitive and physical function decline together on overall disability and health.

Brain predicted age difference mediates pain impact on physical performance in community dwelling middle to older aged adults.

The purpose of the study was to examine associations between physical performance and brain aging in individuals with knee pain and whether the association between pain and physical performance is mediated by brain aging. Participants (n=202) with low impact knee pain (n=111), high impact knee pain (n=60) and pain-free controls (n=31) completed self-reported pain, magnetic resonance imaging (MRI), and a Short Physical Performance Battery (SPPB) that included balance, walking, and sit to stand tasks. Brain predicted age difference, calculated using machine learning from MRI images, significantly mediated the relationships between walking and knee pain impact (CI: -0.124; -0.013), walking and pain-severity (CI: -0.008; -0.001), total SPPB score and knee pain impact (CI: -0.232; -0.025), and total SPPB scores and pain-severity (CI: -0.019; -0.001). Brain-aging begins to explain the association between pain and physical performance, especially walking. This study supports the idea that a brain aging prediction can be calculated from shorter duration MRI sequences and possibly implemented in a clinical setting to be used to identify individuals with pain who are at risk for accelerated brain atrophy and increased likelihood of disability.

Epigenetic age predictors in community-dwelling adults with high impact knee pain.

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.

Autonomic Nervous System Dysregulation and Osteoarthritis Pain: Mechanisms, Measurement, and Future Outlook.

PURPOSE OF REVIEW: The autonomic nervous system is an important regulator of stress responses and exhibits functional changes in chronic pain states. This review discusses potential overlap among autonomic dysregulation, osteoarthritis (OA) progression, and chronic pain. From this foundation, we then discuss preclinical to clinical research opportunities to close gaps in our knowledge of autonomic dysregulation and OA. Finally, we consider the potential to generate new therapies for OA pain via modulation of the autonomic nervous system. RECENT FINDINGS: Recent reviews provide a framework for the autonomic nervous system in OA progression; however, research is still limited on the topic. In other chronic pain states, functional overlaps between the central autonomic network and pain processing centers in the brain suggest relationships between concomitant dysregulation of the two systems. Non-pharmacological therapeutics, such as vagus nerve stimulation, mindfulness-based meditation, and exercise, have shown promise in alleviating painful symptoms of joint diseases, and these interventions may be partially mediated through the autonomic nervous system. The autonomic nervous system appears to be dysregulated in OA progression, and further research on rebalancing autonomic function may lead to novel therapeutic strategies for treating OA pain.

Decreased cognitive function is associated with impaired spatiotemporal gait performance in community dwelling older adults with chronic musculoskeletal pain.

OBJECTIVE: Older adults with chronic musculoskeletal pain often suffer from cognitive impairments and diminished lower extremity physical function. Prior work suggests that these impairments may be interrelated, however, the relationship between cognition and spatiotemporal gait performance in this population is understudied. Therefore, the purpose of this study was to examine the association between cognition and spatiotemporal gait performance and determine if cognition mediates the relationship between pain severity and spatiotemporal gait performance in older adults with chronic musculoskeletal pain without cognitive impairment. METHODS: Older adults with chronic musculoskeletal pain (n = 36) completed the Montreal Cognitive Assessment (MoCA) to assess global cognitive function. Spatiotemporal gait analysis was completed using an automated gait mat. Hierarchical regressions and mediation analyses were used to assess the relationship between chronic musculoskeletal pain, cognition, and spatiotemporal gait performance. RESULTS: MoCA scores were significantly associated with double support time, with lower MoCA scores relating with longer double support times (ß = -0.686, p = 0.039). After accounting for cognition, pain severity was also associated with slower gait speed (ß = -0.422, p = 0.019), and double support time (ß = 0.454, p = 0.008). Cognition, however, did not mediate the relationship between pain severity and double support time. CONCLUSIONS: Global cognition and pain severity were associated with spatiotemporal gait performance in older adults with chronic pain. Pain severity, but not cognition, however, primarily explained spatiotemporal gait performance in our sample. Future work is needed to elucidate the role of cognition in spatiotemporal gait performance in older adults with chronic musculoskeletal pain.

Additional considerations for studying brain metabolite levels across pain conditions using proton magnetic resonance spectroscopy.

Advances in proton magnetic resonance spectroscopy (MRS) allow for the non-invasive examination of neuroinhibitory and neuroexcitatory processes in humans. In particular, these methods have been used to understand changes across chronic pain conditions. While a recent meta-analysis supports the idea that underlying brain metabolite levels may be unique to different pain conditions and may serve as biomarkers for specific pain conditions, the lack of consideration of differential brain aging processes across heterogenous pain conditions introduces a significant source of bias. Future studies need to address the interactions between pain and brain aging across different MRS metabolite measures.

Treatment of localized aggressive periodontitis alters local host immunoinflammatory profiles: A long-term evaluation.

AIM: To evaluate the local immunoinflammatory profiles in localized aggressive periodontitis patients (LAP) before and after periodontal treatment and maintenance. METHODS: Sixty-six African-Americans with LAP (7-21 years old) were included. After periodontal examination, all patients received periodontal treatment with mechanical debridement plus systemic amoxicillin/metronidazole for 7 days. Gingival crevicular fluid was collected from diseased and healthy sites at baseline and 3, 6, 12, and 24 months following treatment. Levels of 16 inflammatory/bone resorption markers were determined using Milliplex® . Univariate and correlation analyses were performed among all parameters/biomarkers. Discriminant analyses (DA) evaluated profile differences between LAP diseased and healthy sites at each time point as compared to the baseline. RESULTS: Reductions in the clinical parameters (except for visible plaque) were observed at all time points compared to the baseline. Levels of IL-12p70, IL-2, IL-6, MIP-1α, RANKL, and OPG were reduced after treatment, and several cytokines/chemokines were correlated with clinical parameters reductions. DA showed that differences in the immunoinflammatory profiles between LAP diseased and healthy sites decreased after periodontal treatment compared to the baseline. CONCLUSIONS: Periodontal treatment modified the local immunoinflammatory profile of LAP sites in the long term, as suggested by changes in biomarkers from baseline, along with clinical stability of the disease. (Clinicaltrials.gov number, NCT01330719).

Pain and the Montreal Cognitive Assessment (MoCA) in Aging.

OBJECTIVE: The present study aimed to determine whether specific cognitive domains part of the Montreal Cognitive Assessment (MoCA) are significantly lower in community-dwelling older adults with chronic pain compared with older adults without pain and whether these domains would be associated with self-reported pain, disability, and somatosensory function. DESIGN: Secondary data analysis, cross-sectional. SETTING: University of Florida. SUBJECTS: Individuals over 60 years old enrolled in the Neuromodulatory Examination of Pain and mobility Across the Lifespan (NEPAL) study were included if they completed the MoCA and other study measures (n = 62). Most participants reported pain on most days during the past three months (63%). METHODS: Subjects underwent a health assessment (HAS) and a quantitative sensory testing (QST) session. Health/medical history, cognitive function and self-reported pain measures were administered during the HAS. Mechanical and thermal detection, and thermal pain thresholds were assessed during the QST session. RESULTS: Older adults with chronic pain had lower MoCA scores compared with controls on domains of executive function, attention, memory, and language (P < 0.05). The attention and language domains survived adjustments for age, sex, education, depression, and pain duration (P < 0.05). Attention was significantly associated with all pain characteristics including pain intensity and disability, while executive function was associated with mechanical detection (P < 0.05). CONCLUSION: Our results support previous findings that individuals with chronic pain tend to show poorer cognitive functioning compared with pain-free controls in domains of attention and executive function. Our findings also extend these findings to community-dwelling older adults, who are already most vulnerable to age-related cognitive declines.

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

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.

A Novel Approach to Characterizing Readmission Patterns Following Hospitalization for Ambulatory Care-Sensitive Conditions.

BACKGROUND: Little is known about the frequency, patterns, and determinants of readmissions among patients initially hospitalized for an ambulatory care-sensitive condition (ACSC). The degree to which hospitalizations in close temporal proximity cluster has also not been studied. Readmission patterns involving clustering likely reflect different underlying determinants than the same number of readmissions more evenly spaced. OBJECTIVE: To characterize readmission rates, patterns, and predictors among patients initially hospitalized with an ACSC. DESIGN: Retrospective analysis of the 2010-2014 Nationwide Readmissions Database. PARTICIPANTS: Non-pregnant patients aged 18-64 years old during initial ACSC hospitalization and who were discharged alive (N = 5,007,820). MAIN MEASURES: Frequency and pattern of 30-day all-cause readmissions, grouped as 0, 1, 2+ non-clustered, and 2+ clustered readmissions. KEY RESULTS: Approximately 14% of patients had 1 readmission, 2.4% had 2+ non-clustered readmissions, and 3.3% patients had 2+ clustered readmissions during the 270-day follow-up. A higher Elixhauser Comorbidity Index was associated with increased risk for all readmission groups, namely with adjusted odds ratios (AORs) ranging from 1.12 to 3.34. Compared to patients aged 80 years and older, those in younger age groups had increased risk of 2+ non-clustered and 2+ clustered readmissions (AOR range 1.27-2.49). Patients with chronic versus acute ACSCs had an increased odds ratio of all readmission groups compared to those with 0 readmissions (AOR range 1.37-2.69). CONCLUSIONS: Among patients with 2+ 30-day readmissions, factors were differentially distributed between clustered and non-clustered readmissions. Identifying factors that could predict future readmission patterns can inform primary care in the prevention of readmissions following ACSC-related hospitalizations.

Resilience factors may buffer cellular aging in individuals with and without chronic knee pain.

Telomere length, a measure of cellular aging, is inversely associated with chronic pain severity. While psychological resilience factors (e.g., optimism, acceptance, positive affect, and active coping) are associated with lower levels of clinical pain and greater physical functioning, it is unknown whether resilience may buffer against telomere shortening in individuals with chronic pain. Additionally, a broader conceptualization of resilience that includes social and biobehavioral factors may improve our understanding of the relationship between resilience, chronic pain, and health outcomes. In individuals with and without chronic knee pain, we investigated whether (1) psychological resilience would be positively associated with telomere length and if (2) a broader conceptualization of resilience including social and biobehavioral factors would strengthen the association. Seventy-nine adults, 45 to 85 years of age, with and without knee pain completed demographic, health, clinical pain, psychological, social, and biobehavioral questionnaires. Resilience levels were determined by summing the total number of measures indicating resilience based on published clinical ranges and norms. Blood samples were collected, and telomere length was determined. In regression analyses controlling for sex, race, age, and characteristic pain intensity, greater psychological resilience and psychosocial/biobehavioral resilience were associated with longer telomeres ( p = .0295 and p = .0116, respectively). When compared, psychosocial/biobehavioral resilience was significantly more predictive of telomere length than psychological resilience ( p < .0001). Findings are promising and encourage further investigations to enhance understanding of the biological interface of psychosocial and biobehavioral resilience factors in individuals with musculoskeletal chronic pain conditions.

Single Nucleotide Polymorphism in the COL11A2 Gene Associated with Heat Pain Sensitivity in Knee Osteoarthritis.

Abstract: Pain is one of the most prominent symptoms of osteoarthritis. However, there is often discordance between the pain experienced by individuals with osteoarthritis and the degree of articular pathology. This suggests that individual differences, including genetic variability in the central processing of nociceptive stimuli, may impact the presentation of osteoarthritis. Here, we show that the single nucleotide polymorphism rs16868943 in the collagen gene COL11A2 is significantly associated with lowered heat pain tolerance on the arm in participants with knee osteoarthritis (P = 1.21 × 10−6, P = 0.0053 after Bonferroni correction, beta = −3.42). A total of 161 knee osteoarthritis participants were included and evaluated for heat, punctate and pressure pain sensitivity of the affected knee and the ipsilateral arm. Each participant was genotyped for 4392 single nucleotide polymorphisms in genes implicated in pain perception, inflammation and mood and tested for association with pain sensitivity. The minor A allele of single nucleotide polymorphism rs16868943 was significantly associated with lower arm heat pain tolerance after correction for age, gender, race, and study site. This single nucleotide polymorphism was also nominally associated with other measures of heat pain sensitivity, including lowered knee heat pain tolerance (P = 1.14 × 10−5, P = 0.05 after Bonferroni correction), lowered arm heat pain threshold (P = 0.0039, uncorrected) and lowered knee heat pain threshold (P = 0.003, uncorrected). Addition of genotypes from 91 participants without knee pain produced a significant interaction between knee osteoarthritis status and the rs16868943 single nucleotide polymorphism in heat pain tolerance (P = 1.71 × 10−5), such that rs16868943 was not associated with heat pain tolerance in participants without knee pain (P = 0.12, beta = 1.3). This is the first study to show genetic association with heat pain tolerance in individuals with osteoarthritis. The association is specific to participants who have already developed knee osteoarthritis, suggesting that the COL11A2 gene, which has previously been associated with familial osteoarthritis, may play a role in pain sensitization after the development of osteoarthritis.

Reliability of pain intensity clamping using response-dependent thermal stimulation in healthy volunteers.

BACKGROUND: Pain intensity clamping uses the REsponse-Dependent Stimulation (REDSTIM) methodology to automatically adjust stimulus intensity to maintain a desired pain rating set-point which is continuously monitored from a subject's real-time pain ratings. REDSTIM blinds subjects regarding the pain intensity set-point, supporting its use for assessing intervention efficacy. By maintaining the pain intensity at a constant level, a potential decrease in pain sensitivity can be detected by an increase in thermode temperature (unknown to the subject) and not by pain ratings alone. Further, previously described sensitizing and desensitizing trends within REDSTIM provide a novel insight into human pain mechanisms overcoming limitations of conventional testing methods. The purpose of the present study was to assess the test-retest reliability of pain intensity clamping using REDSTIM during three separate sessions. METHODS: We used a method for testing changes in pain sensitivity of human subjects (REDSTIM) where the stimulus temperature is modulated to clamp pain intensity near a desired set-point. Temperature serves as the response variable and is used to infer pain sensitivity. Several measures were analyzed for reliability including average temperature and area under the curve (AUC). Intraclass correlation coefficients were calculated for each measure at pain rating set-points of 20/100 and 35/100. RESULTS: Sixteen healthy individuals (mean age = 21.6 ± 3.9) participated in three experiments two days apart at both pain rating set-points. Most reliability coefficients were in the moderate to substantial range (r's = 0.79 to 0.94) except for the negative AUC (r = 0.52), but only at the 20/100 pain rating set-point. CONCLUSIONS: The present study supports the test-retest reliability of pain intensity clamping using the REDSTIM methodology while providing a novel tool to examine human pain modulatory mechanisms and overcoming common shortcomings of conventional quantitative sensory testing methods.

Temporal summation of pain as a prospective predictor of clinical pain severity in adults aged 45 years and older with knee osteoarthritis: ethnic differences.

OBJECTIVE: Enhanced pain facilitation is reportedly an important contributor to the clinical pain experiences of individuals with knee osteoarthritis (OA). Ethnic differences in the prevalence and severity of knee OA in addition to associated pain are also well documented. Temporal summation (TS) of pain is a widely applicable quantitative sensory testing method that invokes neural mechanisms related to pain facilitatory processes. This study tested whether TS of pain, an index of pain facilitation, differentially predicts the clinical pain experiences of African Americans and non-Hispanic whites with symptomatic knee OA. METHODS: A total of 225 study participants underwent assessment of TS of mechanical and heat pain stimuli applied to their most symptomatic knee and their ipsilateral hand (mechanical) or forearm (heat). Using telephone-based surveys, participants subsequently reported their average and worst clinical pain severity across four consecutive weeks after the assessment of TS. RESULTS: In predicting future clinical pain, ethnicity interacted with TS of mechanical pain (but not heat pain), such that TS of mechanical pain at the knee significantly predicted greater clinical ratings of average (b = 0.02, p = .016) and worst (b = 0.02, p = .044) clinical pain for non-Hispanic whites but not African Americans (p values > .30). CONCLUSIONS: These results reveal the importance of considering ethnicity when examining pain facilitation and the clinical pain of individuals with symptomatic knee OA. The results of this study are discussed in terms of ethnic differences in the predictors of clinical pain experiences among African Americans and non-Hispanic whites with knee OA.

Pain hypervigilance is associated with greater clinical pain severity and enhanced experimental pain sensitivity among adults with symptomatic knee osteoarthritis.

BACKGROUND: Pain hypervigilance is an important aspect of the fear-avoidance model of pain that may help explain individual differences in pain sensitivity among persons with knee osteoarthritis (OA). PURPOSE: The purpose of this study was to examine the contribution of pain hypervigilance to clinical pain severity and experimental pain sensitivity in persons with symptomatic knee OA. METHODS: We analyzed cross-sectional data from 168 adults with symptomatic knee OA. Quantitative sensory testing was used to measure sensitivity to heat pain, pressure pain, and cold pain, as well as temporal summation of heat pain, a marker of central sensitization. RESULTS: Pain hypervigilance was associated with greater clinical pain severity, as well as greater pressure pain. Pain hypervigilance was also a significant predictor of temporal summation of heat pain. CONCLUSIONS: Pain hypervigilance may be an important contributor to pain reports and experimental pain sensitivity among persons with knee OA.

Can quantitative sensory testing move us closer to mechanism-based pain management?

OBJECTIVE: This review summarizes the scientific literature relating to the use of quantitative sensory testing (QST) for mechanism-based pain management. DESIGN: A literature search was undertaken using PubMed and search terms including quantitative sensory testing, pain, chronic pain, response to treatment, outcome measure. SETTINGS AND PATIENTS: Studies including QST in healthy individuals and those with painful disorders were reviewed. MEASURES: Publications reported on QST methodological issues including associations among measures and reliability. We also included publications on the use of QST measures in case-control studies, their associations with biopsychosocial mechanisms, QST measures predicting clinical pain, as well as predicting and reflecting treatment responses. RESULTS: Although evidence suggests that QST may be useful in a mechanism-based classification of pain, there are gaps in our current understanding that need to be addressed including making QST more applicable in clinical settings. There is a need for developing shorter QST protocols that are clinically predictive of various pain subtypes and treatment responses without requiring expensive equipment. Future studies are needed, examining the clinical predictive value of QST including sensitivity and specificity for pain classification or outcome prediction. These findings could enable third-party payers' reimbursement, which would facilitate clinical implementation of QST. CONCLUSIONS: With some developments, QST could become a cost-effective and clinically useful component of pain assessment and diagnosis, which can further our progress toward the goal of mechanism-based personalized pain management.

Food insecurity and epigenetic aging in middle-aged and older adults.

BACKGROUND: Food insecurity is recognized as a key social determinant of health for older adults. While food insecurity has been associated with morbidity and mortality, few studies have examined how it may contribute to accelerated biological aging. A potential mechanism by which food insecurity may contribute to aging is via epigenetic alterations. We examined the relationship between food insecurity and epigenetic aging, a novel measure of biological aging, in a nationally representative sample of middle-aged and older adults in the United States. METHODS: Cross-sectional analysis of adults 50 years of age and older from the 2016 Health and Retirement Study (HRS). Financial food insecurity was self-reported via two questions that ascertained having enough money for food or eating less than they felt they should. Epigenetic aging was measured via epigenetic clocks based on DNA methylation patterns that predict aging correlates of morbidity and mortality. Linear regressions were performed to test for differences in the epigenetic clocks, adjusting for biological, socioeconomic, and behavioral factors. RESULTS: The analysis consisted of 3875 adults with mean age of 68.5 years. A total of 8.1% reported food insecurity. Food insecurity was associated with several characteristics, including younger age, race/ethnic minority, lower income, total wealth, and educational attainment, higher BMI, and less physical activity. Food insecurity was associated with accelerated epigenetic aging compared to food security, as measured via second (Zhang, PhenoAge, GrimAge) and third (DunedinPoAm) generation epigenetic clocks. In particular, food insecurity remained significantly associated with accelerated Zhang (B = 0.09, SE = 0.03, p = 0.011) and GrimAge (B = 0.57, SE = 0.24, p = 0.022) in the fully adjusted models. CONCLUSIONS: Food insecurity is associated with accelerated epigenetic aging among middle-aged and older adults in the United States. Food insecurity may contribute to DNA methylation alterations across the genome and biological age acceleration. These findings add to a growing understanding of the influence of socioeconomic status on the epigenome and health in aging.

High-Impact Pain Is Associated With Epigenetic Aging Among Middle-Aged and Older Adults: Findings From the Health and Retirement Study.

BACKGROUND: Chronic pain has been associated with accelerated biological aging, which may be related to epigenetic alterations. We evaluated the association of high-impact pain (ie, pain that limits activities and function) with epigenetic aging, a measure of biological aging, in a nationally representative sample of middle-aged and older adults in the United States. METHODS: Cross-sectional analysis of adults 50 years of age and older from the 2016 Health and Retirement Study. Epigenetic aging was derived from 13 epigenetic clocks based on DNA methylation patterns that predict aging correlates of morbidity and mortality. Ordinary least squares regressions were performed to test for differences in the epigenetic clocks, adjusting for the complex survey design, as well as biological, social, and behavioral factors. RESULTS: The analysis consisted of 3 855 adults with mean age of 68.5 years, including 59.8% with no pain and 25.8% with high-impact pain. Consistent with its operational definition, high-impact pain was associated with greater functional and activity limitations. High-impact pain was associated with accelerated epigenetic aging compared to no pain, as measured via second (Zhang, PhenoAge, GrimAge) and third (DunedinPoAm) generation epigenetic clocks. Additionally, GrimAge was accelerated in high-impact pain as compared to low-impact pain. CONCLUSIONS: High-impact pain is associated with accelerated epigenetic aging among middle-aged and older adults in the United States. These findings highlight aging-associated epigenetic alterations in high-impact chronic pain and suggest a potential for epigenetic therapeutic approaches for pain management and the preservation of physical function in older adults.