Disadvantaged socioeconomic position (SEP) is associated with increased systemic inflammation. However, the mechanisms and potential persistence of these molecular differences remain poorly understood. We investigated the association between educational attainment, an indicator of SEP, and the levels of 52 plasma inflammatory proteins measured in the same individuals seven to eight years apart. We analyzed data from 909 participants of the sixth (2007–2008) and seventh (2015–2016) waves of the Tromsø Study, a longitudinal population-based study in Tromsø, Norway. Inflammatory protein levels were measured using the Olink Target 96 Inflammation panel and educational attainment was retrieved from questionnaires. Cross-sectional and longitudinal associations between educational attainment and inflammatory protein levels were assessed using multivariable linear models and linear mixed models, respectively. We identified a consistent association between higher educational attainment and lower levels of CCL20, CDCP1, and HGF, and higher levels of CST5 at both waves (FDR < 0.1). In addition, we observed that higher educational attainment was associated with lower levels of CCL19, IL-6, and OSM, and higher levels of FGF19 at the second wave only. Nonetheless, all associations were attenuated after adjustment for lifestyle factors, body-mass index, health conditions, and medication. Longitudinal analyses indicated a stable educational gradient across the two waves, with no significant changes in the association between educational attainment and inflammatory protein levels. Our findings indicate a stable educational gradient in the levels of several plasma proteins involved in cell migration, growth, and tissue remodeling in adults, across the seven-to-eight-year period, with modifiable lifestyle factors and body-mass index substantially attenuating the education-protein associations.
Background Bipolar disorder (BD) has been associated with biomarkers of ageing and of inflammation with little information about associations between markers. Method Using blood samples of 139 individuals with BD, we generated Horvath, Hannum, EN, GrimAge and PhenoAge epigenetic ages and used a latent profile analysis to construct subgroups of individuals based on their profile of epigenetic age accelerations. In blood samples, we measured telomere length (TL), mitochondrial DNA copy number (mtDNAcn), and 29 markers of inflammation of which 18 were analyzed. Results Univariate analyses showed higher levels of IL-16, IL-7, IL-10, IL-1RA, IL-12-IL-23p40, TNF-alpha, TNF-R1, ICAM-1, VCAM-1 and HLA-E in the epigenetically older group, and negative correlations between mtDNAcn and TNF-alpha, IP-10, VCAM-1 and IL-6R and one positive correlation between TL and IL-15. After Bonferroni correction, the associations between the epigenetically older group, IL-16 and HLA-E remained significant (p < 0.001). After adjustment for confounding variables, multivariate analyses confirmed an association between the epigenetically older group and higher levels of IL-16 (p = 0.001). Analyses of methylation of the IL-16 gene (26 sites) suggested that a lower methylation of cg20700699, located in an enhancer region, was associated with a higher level of IL-16 in the blood (p < 0.001). Conclusions This study identified that an epigenetically older subgroup of individuals with BD were characterized by higher IL-16 blood levels. IL-16 may act as a central mediator linking immune activation, chronic inflammation, and accelerated biological ageing. If replicated, these results might support the concept of “inflamm-ageing” in BD.
Early life stress (ELS) is highly prevalent among women with HIV (WWH) and contributes to risk for brain health disorders. Mitochondria represent key regulators of cellular stress processes and may represent a key mechanism linking ELS to biological vulnerability. While mitochondrial dysfunction has been associated with ELS in other populations, it remains unknown whether ELS is related to multidimensional mitochondrial health in WWH. Thus, we examined associations between ELS and mitochondrial health metrics in WWH. Sixty-one WWH completed the Childhood Trauma Questionnaire (CTQ) and provided blood samples. Plasma and peripheral blood mononuclear cells (PBMCs) were isolated and used to assess mitochondrial bioenergetic function (Seahorse Cell Mito Stress Test), mitochondrial DNA copy number (mtDNAcn, qPCR), mtDNA integrity (qPCR), cell free mitochondrial DNA (cf-mtDNA, qPCR), and static mitochondrial protein expression (western blots). Linear regression models were used to evaluate associations between CTQ scores and mitochondrial outcomes. Higher CTQ scores were associated with increased basal respiration (β = 0.824, p = 0.012, q = 0.028), maximal respiration (β = 3.716, p = 0.014, q = 0.028), and spare respiratory capacity (β = 2.844, p = 0.026, q = 0.031). Conversely, higher CTQ scores were associated with lower mtDNAcn (β = − 2.369, p = 0.009, q = 0.018). No associations were observed with mtDNA integrity, cf-mtDNA, or mitochondrial protein expression. These findings demonstrate a divergent mitochondrial phenotype in WWH exposed to ELS, characterized by increased respiratory activity despite reduced mtDNA copy number. Mitochondrial health is potentially an integral consideration for understanding the link between ELS and biological vulnerability.
Background Sepsis disproportionately causes long-term cognitive and functional impairments in elderly survivors, including deficits in activities of daily living and functional independence. The neurobiological mechanisms driving this vulnerability in the aged brain remain poorly understood. We tested whether the aged brain possesses a unique vulnerability to sepsis-induced impairment in the early post-acute recovery period. Methods Polymicrobial sepsis was induced in young (3-months) and aged (18-months) mice via cecal slurry injection, with dosing adjusted for comparable acute illness severity. Behavioral assessments (learning, memory, locomotion, innate behaviors) were performed through Day 7 post-infection. On Day 8, brains were analyzed for inflammatory cytokines, glial activation, neuronal protein expression, and blood–brain barrier (BBB) permeability. Results Aged septic mice exhibited alterations in nest building and sociability, whereas young mice with comparable illness severity remained behaviorally resilient. The behavioral changes in aged mice occurred in the absence of broad systemic or neuroinflammation. Conversely, young septic mice maintained normal behavior despite significantly elevated systemic and neuroinflammation. Aged mice displayed signs of glial activation, neuronal protein modulation, and BBB permeability compared to young mice, but sepsis did not significantly exacerbate these markers in either group. Conclusion Our findings demonstrate an age-dependent divergence in neurologic recovery after sepsis: while young mice exhibit behavioral resilience despite systemic and neuroinflammation, aged mice display alterations in innate behavior that are present even after the apparent resolution of acute illness. This suggests that the changes in innate behavior in the aged mice are not driven solely by sepsis-induced inflammation, but rather by a cumulative burden of age-related vulnerabilities, including microglial priming, astrocytic activation, and increased BBB permeability, that render aged brains unable to compensate for a severe acute physiological challenge.
