Methionine restriction (MR) has been studied extensively over the last 25 years for its role in altering metabolic hallmarks of disease. Animals subjected to MR, display changes in metabolic flexibility demonstrated by increases in energy expenditure, glucose tolerance, and lifespan. These changes have been well characterized in a number of model systems and significant progress has been made in understanding how hepatic fibroblast growth factor 21 links MR to several components of its metabolic phenotype. Despite these advances, a complete understanding of mechanisms engaged by dietary MR remains elusive. In this review, we offer a brief history of MR and its known mechanisms associated with stress, metabolism, and lifespan extension. We consider the role of epigenetics in the response of animals to MR and propose a novel epigenetic pathway involving the regulation of microRNAs during MR.

• The pace of biological aging (DunedinPACE) positively correlates with the internalized stigma of chronic pain and pain severity and interference. • The pace of biological aging mediates the relationship between internalized stigma and nonspecific chronic low back pain (CLBP). • The indirect relationship of internalized stigma with nonspecific CLBP is significant for non-Hispanic Black but not for non-Hispanic White adults.

There is growing evidence that psychological (e.g., optimism, pessimism, depressive symptoms) and biological factors play an essential role in the experience of chronic low back pain (CLBP). This study aimed to examine the nature of the relationship between optimism or pessimism, depressive symptoms, the pace of biological aging, CLBP severity, and interference. Using mediation analysis, we tested the hypothesis that depressive symptoms and pace of biological aging measured using the Dunedin Pace of Aging from the Epigenome (DunedinPACE) serially mediate the relationship between optimism or pessimism and CLBP severity and interference. Our sample included non-Hispanic Black and non-Hispanic White adults aged 18–82 years: 74 without pain, 56 with low-impact pain, and 77 with high-impact pain. On average, individuals with high-impact pain reported lower levels of optimism, greater pessimism, and faster DunedinPACE than those in the low-impact or no-pain group ( p < .05). Mediation analyses revealed indirect associations between both optimism and pessimism with pain severity and interference serially via depressive symptoms and the pace of biological aging ( p < .05). These indirect effects were not statistically significant after controlling for chronological age, sex, race, and BMI. The results suggest that psychological interventions that increase optimism and reduce pessimism may slow the biological aging process, which may improve nonspecific CLBP outcomes in non-Hispanic Black and non-Hispanic White adults.

In this study, we aimed to investigate if the pace of biological aging serves as a critical mediator in the relationship between chronic pain resilience and chronic low back pain intensity and disability. Two hundred seven community-dwelling non-Hispanic Black (NHB) and non-Hispanic White (NHW) adults completed the Pain Resilience Scale (PRS) and Graded Chronic Pain Scale (GCPS). Blood genomic DNA was sequenced using Illumina’s MethylationEPIC, and the pace of biological aging estimated using the DunedinPACE (the Dunedin Pace of Aging Calculated from the Epigenome) algorithm. In bivariate correlations, DunedinPACE significantly correlated with pain intensity (r = 0.40), and disability (r = 0.39), at p < .05. Pain resilience negatively correlated with pain intensity (rs = −0.22), pain disability (rs = −0.30), and DunedinPACE (r = −0.11). After controlling for chronological age, sex, race, and BMI, mediation analyses revealed a significant indirect association of pain resilience on pain intensity through the pace of biological aging (β = −0.66 (SE); Boot 95% CI [−1.06, −0.25]). Similarly, DunedinPACE partially mediated the relationship between resilience and pain disability (β = −0.82; 95% CI, [−1.20 to −0.44]). We found that higher levels of resilience correlate with a slower pace of biological aging, which in turn correlates with better pain outcomes. The pace of biological aging emerged as an important potential target for future interventions studies for pain management.

Background: Chronic low back pain (CLBP) directly causes reduced work productivity and increased absenteeism, disability, and health care costs. However, further research is necessary to identify whether employment correlates with better health outcomes for workers with CLBP. Objective: We aimed to explore differences in biological, psychological, and social variables between individuals with CLBP who have employment and those who receive disability benefits. Methods: This exploratory cross-sectional study used data from adults with nonspecific CLBP (15 employed and 10 receiving disability benefits) who are part of an ongoing study of epigenetics and gene expression signatures of racial and socioeconomic status disparities. Data were collected on depressive symptoms, perceived injustice, internalized stigma, social support, life orientation, pain intensity, pain interference, and various measures of biological aging. Results: On average, unemployed individuals (receiving disability benefits) reported significantly higher levels of internalized stigma of chronic pain ( t ₂₃ = −2.282, p = .016), pessimism ( t ₂₃ = −2.646, p = .007), insomnia severity ( t ₂₃ = −4.201, p < .001), perceived injustice ( t ₂₃ = −4.108, p < .001), depressive symptoms ( t ₂₃ = −4.195, p < .001), pain intensity ( t ₂₃ = −4.195, p < .001), and pain interference ( t ₂₃ = −5.288, p < .001), but lower pain resilience ( t ₂₃ = 3.422, p = .001) than participants who were employed. On average, participants receiving disability benefits had GrimAge epigenetic age acceleration, while employed participants had epigenetic age deceleration ( t ₂₁ = −2.256, p = .017). Conclusion: Among individuals living with CLBP, employment may be associated with a more positive health outcome. To foster an active and healthy workforce, it is essential to understand the biological, psychological, and social factors affecting employment status when addressing CLBP.

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.