RESUMO
BACKGROUND: Genetic copy number variants (CNVs; i.e., a deletion or duplication) at the 22q11.2 locus confer increased risk of neuropsychiatric disorders and immune dysfunction. Inflammatory profiles of 22q11.2 CNV carriers can shed light on gene-immune relationships that may be related to neuropsychiatric symptoms. However, little is known about inflammation and its relationship to clinical phenotypes in 22q11.2 CNV carriers. Here, we investigate differences in peripheral inflammatory markers in 22q11.2 CNV carriers and explore their relationship with psychosis risk symptoms and sleep disturbance. METHODS: Blood samples and clinical assessments were collected from 22q11.2 deletion (22qDel) carriers (n=45), 22q11.2 duplication (22qDup) carriers (n=29), and typically developing (TD) control participants (n=92). Blood plasma levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and anti-inflammatory cytokine interleukin-10 (IL-10) were measured using a MesoScale Discovery multiplex immunoassay. Plasma levels of C-reactive protein (CRP) were measured using Enzyme-linked Immunosorbent Assay (ELISA). Linear mixed effects models controlling for age, sex, and body mass index were used to: a) examine group differences in inflammatory markers between 22qDel, 22qDup, and TD controls, b) test differences in inflammatory markers between 22qDel carriers with psychosis risk symptoms (22qDelPS+) and those without (22qDelPS-), and c) conduct an exploratory analysis testing the effect of sleep disturbance on inflammation in 22qDel and 22qDup carriers. A false discovery rate correction was used to correct for multiple comparisons. RESULTS: 22qDup carriers exhibited significantly elevated levels of IL-8 relative to TD controls (q<0.001) and marginally elevated IL-8 levels relative to 22qDel carriers (q=0.08). There were no other significant differences in inflammatory markers between the three groups (q>0.13). 22qDelPS+ exhibited increased levels of IL-8 relative to both 22qDelPS- (q=0.02) and TD controls (p=0.002). There were no relationships between sleep and inflammatory markers that survived FDR correction (q>0.14). CONCLUSION: Our results suggest that CNVs at the 22q11.2 locus may have differential effects on inflammatory processes related to IL-8, a key mediator of inflammation produced by macrophages and microglia. Further, these IL-8-mediated inflammatory processes may be related to psychosis risk symptoms in 22qDel carriers. Additional research is required to understand the mechanisms contributing to these differential levels of IL-8 between 22q11.2 CNV carriers and IL-8's association with psychosis risk.
RESUMO
PURPOSE: Neighborhoods represent complex environments with unique social, cultural, physical, and economic attributes that have major impacts on disparities in health, disease, and survival. Neighborhood disadvantage is associated with shorter breast cancer recurrence-free survival (RFS) independent of individual-level (race, ethnicity, socioeconomic status, insurance, tumor characteristics) and health system-level determinants of health (receipt of guideline-concordant treatment). This persistent disparity in RFS suggests unaccounted mechanisms such as more aggressive tumor biology among women living in disadvantaged neighborhoods compared with advantaged neighborhoods. The objective of this article was to provide a clear framework and biological mechanistic explanation for how neighborhood disadvantage affects cancer survival. METHODS: Development of a translational epidemiological framework that takes a translational disparities approach to study cancer outcome disparities through the lens of social genomics and social epigenomics. RESULTS: The social genomic determinants of health, defined as the physiological gene regulatory pathways (ie, neural/endocrine control of gene expression and epigenetic processes) through which contextual factors, particularly one's neighborhood, can affect activity of the cancer genome and the surrounding tumor microenvironment to alter disease progression and treatment outcomes. CONCLUSION: We propose a novel, multilevel determinants of health model that takes a translational epidemiological approach to evaluate the interplay between political, health system, social, psychosocial, individual, and social genomic determinants of health to understand social disparities in oncologic outcomes. In doing so, we provide a concrete biological pathway through which the effects of social processes and social epidemiology come to affect the basic biology of cancer and ultimately clinical outcomes and survival.
RESUMO
Discrimination is a social determinant of health and health disparities for which the biological mechanisms remain poorly understood. This study investigated the hypothesis that discrimination contributes to poor health outcomes by accelerating biological processes of aging. We analyzed survey and blood DNA methylation data from the Midlife in the United States (MIDUS) study (N = 1967). We used linear regression analysis to test associations of everyday, major, and workplace discrimination with biological aging measured by the DunedinPACE, PhenoAge, and GrimAge2 epigenetic clocks. MIDUS participants who reported more discrimination tended to exhibit a faster pace of aging and older biological age as compared to peers who reported less discrimination. Effect-sizes for associations tended to be larger for the DunedinPACE pace-of-aging clock (effect-size range r = 0.1-0.2) as compared with the PhenoAge and GrimAge2 biological-age clocks (effect-sizes r < 0.1) and for experiences of everyday and major discrimination as compared with workplace discrimination. Smoking status and body-mass index accounted for roughly half of observed association between discrimination and biological aging. Reports of discrimination were more strongly associated with accelerated biological aging among White as compared with Black participants, although Black participants reported more discrimination overall and tended to exhibit older biological age and faster biological aging. Findings support the hypothesis that experiences of interpersonal discrimination contribute to accelerated biological aging and suggest that structural and individual-level interventions to reduce discrimination and promote adaptive coping have potential to support healthy aging and build health equity.
RESUMO
Low socioeconomic status (SES) is a risk factor for mortality and immune dysfunction across a wide range of diseases, including cancer. However, cancer is distinct in the use of allogeneic hematopoietic cell transplantation (HCT) as a treatment for hematologic malignancies to transfer healthy hematopoietic cells from one person to another. This raises the question of whether social disadvantage of an HCT cell donor, as assessed by low SES, might impact the subsequent health outcomes of the HCT recipient. To evaluate the cellular transplantability of SES-associated health risk, we analyzed the health outcomes of 2,005 HCT recipients who were transplanted for hematologic malignancy at 125 United States transplant centers and tested whether their outcomes differed as a function of their cell donor's SES (controlling for other known HCT-related risk factors). Recipients transplanted with cells from donors in the lowest quartile of SES experienced a 9.7% reduction in overall survival (P = 0.001) and 6.6% increase in treatment-related mortality within 3 y (P = 0.008) compared to those transplanted from donors in the highest SES quartile. These results are consistent with previous research linking socioeconomic disadvantage to altered immune cell function and hematopoiesis, and they reveal an unanticipated persistence of those effects after cells are transferred into a new host environment. These SES-related disparities in health outcomes underscore the need to map the biological mechanisms involved in the social determinants of health and develop interventions to block those effects and enhance the health of both HCT donors and recipients.
Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/mortalidade , Fatores de Risco , Classe Social , Estados Unidos/epidemiologia , Idoso , Adolescente , Doadores de TecidosRESUMO
Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these "silent" symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of systemic inflammatory biology. To address these issues, we conducted a prospective, observational pilot study to investigate the psychological, biological, and neuroarchitecture changes associated with a mindfulness-based stress reduction (MBSR) program in MS. The overarching hypothesis was that MBSR modulates systemic and central nervous system inflammation via top-down neurocognitive control over forebrain limbic areas responsible for the neurobiological stress response. 23 patients were enrolled in MBSR and assessed pre/post-program with structural 3 T MRI, behavioral measures, hair cortisol, and blood measures of peripheral inflammation, as indexed by the Conserved Transcriptional Response to Adversity (CTRA) profile. MBSR was associated with improvements across a variety of behavioral outcomes, as well as on-study enlargement of the head of the right hippocampus. The CTRA analyses revealed that greater inflammatory gene expression was related to worse patient-reported anxiety, depression, stress, and loneliness, in addition to lower eudaimonic well-being. Hair cortisol did not significantly change from pre- to post-MBSR. These results support the use of MBSR in MS and elucidate inflammatory mechanisms related to key patient-reported outcomes in this population.
Assuntos
Imageamento por Ressonância Magnética , Atenção Plena , Esclerose Múltipla , Estresse Psicológico , Humanos , Feminino , Atenção Plena/métodos , Projetos Piloto , Masculino , Pessoa de Meia-Idade , Adulto , Esclerose Múltipla/psicologia , Esclerose Múltipla/terapia , Esclerose Múltipla/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Inflamação , Estudos Prospectivos , Hidrocortisona/metabolismo , Hidrocortisona/sangue , Qualidade de VidaRESUMO
There is urgent need for novel antidepressant treatments that confer therapeutic benefits via engagement with identified mechanistic targets. The objective of the study was to determine whether activation of the classical anti-inflammatory interleukin-6 signaling pathways is associated with the antidepressant effects of whole-body hyperthermia. A 6-week, randomized, double-blind study compared whole-body hyperthermia with a sham condition in a university-based medical center. Medically healthy participants aged 18-65 years who met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score ≥ 16 were randomized with 1-to-1 allocation in blocks of 6 to receive whole-body hyperthermia or sham. Of 338 individuals screened, 34 were randomized, 30 received interventions and 26 had ≥ 2 blood draws and depressive symptom assessments. Secondary data analysis examined change in the ratio of IL-6:soluble IL-6 receptor pre-intervention, post-intervention, and at weeks 1 and 4. Hierarchical linear modeling tested whether increased IL-6:soluble IL-6 receptor ratio post-intervention was associated with decreased depressive symptom at weeks 1, 2, 4 and 6 for those randomized to whole-body hyperthermia. Twenty-six individuals were randomized to whole-body hyperthermia [n = 12; 75 % female; age = 37.9 years (SD = 15.3) or sham [n = 14; 57.1 % female; age = 41.1 years (SD = 12.5). When compared to the sham condition, active whole-body hyperthermia only increased the IL-6:soluble IL-6 receptor ratio post-treatment [F(3,72) = 11.73,p < .001], but not pre-intervention or at weeks 1 and 4. Using hierarchical linear modeling, increased IL-6:sIL-6R ratio following whole-body hyperthermia moderated depressive symptoms at weeks 1, 2, 4 and 6, such that increases in the IL-6:soluble IL-6 receptor ratio were associated with decreased depressive symptoms at weeks 1, 2, 4 and 6 for those receiving the active whole-body hyperthermia compared to sham treatment (B = -229.44, t = -3.82,p < .001). Acute activation of classical intereukin-6 signaling might emerge as a heretofore unrecognized novel mechanism that could be harnessed to expand the antidepressant armamentarium.
Assuntos
Transtorno Depressivo Maior , Interleucina-6 , Receptores de Interleucina-6 , Transdução de Sinais , Humanos , Feminino , Masculino , Interleucina-6/sangue , Adulto , Método Duplo-Cego , Pessoa de Meia-Idade , Transdução de Sinais/efeitos dos fármacos , Transtorno Depressivo Maior/terapia , Receptores de Interleucina-6/metabolismo , Hipertermia Induzida/métodos , Adulto Jovem , Adolescente , Resultado do Tratamento , Idoso , Hipertermia , Antidepressivos/uso terapêutico , Antidepressivos/farmacologiaRESUMO
OBJECTIVE: Although rural residence has been related to health disparities in cancer patients, little is known about how rural residence impacts mental health and quality of life (QOL) in ovarian cancer patients over time. This prospective longitudinal study investigated mental health and QOL of ovarian cancer patients in the first-year post-diagnosis. METHOD: Women with suspected ovarian cancer completed psychosocial surveys pre-surgery, at 6 months and one-year; clinical data were obtained from medical records. Histologically confirmed high grade epithelial ovarian cancer patients were eligible. Rural/urban residence was categorized from patient counties using the USDA Rural-Urban Continuum Codes. Linear mixed effects models examined differences in psychosocial measures over time, adjusting for covariates. RESULTS: Although disparities were not observed at study entry for any psychosocial variable (all p-values >0.22), urban patients showed greater improvement in total distress over the year following diagnosis than rural patients (p = 0.025) and were significantly less distressed at one year (p = 0.03). Urban patients had a more consistent QOL improvement than their rural counterparts (p = 0.006). There were no differences in the course of depressive symptoms over the year (p = 0.17). Social support of urban patients at 12 months was significantly higher than that of rural patients (p = 0.04). CONCLUSION: Rural patients reported less improvement in psychological functioning in the year following diagnosis than their urban counterparts. Clinicians should be aware of rurality as a potential risk factor for ongoing distress. Future studies should examine causes of these health disparities and potential long-term inequities and develop interventions to address these issues.
Assuntos
Carcinoma Epitelial do Ovário , Depressão , Neoplasias Ovarianas , Funcionamento Psicossocial , Disparidades nos Níveis de Saúde , Carcinoma Epitelial do Ovário/psicologia , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Ovarianas/psicologia , População Urbana , População Rural , Apoio Social , Qualidade de Vida , Estudos Longitudinais , Saúde Mental , Estudos Prospectivos , Angústia Psicológica , Depressão/psicologia , Características de ResidênciaRESUMO
Disparities in socio-economic status (SES) predict many immune system-related diseases, and previous research documents relationships between SES and the immune cell transcriptome. Drawing on a bioinformatically-informed network approach, we situate these findings in a broader molecular framework by examining the upstream regulators of SES-associated transcriptional alterations. Data come from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative sample of 4543 adults in the United States. Results reveal a network-of differentially expressed genes, transcription factors, and protein neighbors of transcription factors-that shows widespread SES-related dysregulation of the immune system. Mediational models suggest that body mass index (BMI) plays a key role in accounting for many of these associations. Overall, the results reveal the central role of upstream regulators in socioeconomic differences in the molecular basis of immunity, which propagate to increase risk of chronic health conditions in later-life.
Assuntos
Classe Social , Transcriptoma , Adulto , Adolescente , Humanos , Estados Unidos , Estudos Longitudinais , Perfilação da Expressão Gênica , Fatores de Transcrição/genética , Fatores SocioeconômicosRESUMO
INTRODUCTION: Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers. METHOD: Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey items from established scales (Center for Epidemiological Studies Depression Scale; Profile of Mood States, Functional Assessment of Cancer Therapy). Two hopeless items were z-scored and combined into a composite for analysis. Regression models related these variables to nocturnal cortisol, cortisol slope, plasma and ascites IL-6, adjusting for cancer stage, BMI, age, and depression. RESULTS: Greater hope was significantly related to a steeper cortisol slope, ß = -0.193, p = 0.046, and lower night cortisol, ß = -0.227, p = 0.018, plasma IL-6, ß = -0.142, p = 0.033, and ascites IL-6, ß = -0.290, p = 0.002. Secondary analyses including both hope and hopelessness showed similar patterns, with distinct relationships of hope with significantly lower nocturnal cortisol ß = -0.233,p = 0.017 and ascites IL-6, ß = -0.282,p = 0.003, and between hopelessness and a flatter cortisol slope, ß = 0.211, p = 0.031. CONCLUSIONS: These data suggest a biological signature of hope associated with less inflammation and more normalized diurnal cortisol in ovarian cancer. These findings have potential clinical utility but need replication with more diverse samples and validated assessments of hope.
Assuntos
Hidrocortisona , Neoplasias Ovarianas , Humanos , Feminino , Hidrocortisona/análise , Depressão , Interleucina-6/análise , Ascite , Biomarcadores , Biologia , Saliva/química , Ritmo CircadianoRESUMO
Up to 40 % of individuals who sustain traumatic injuries are at risk for posttraumatic stress disorder (PTSD) and the conditional risk for developing PTSD is even higher for Black individuals. Exposure to racial discrimination, including at both interpersonal and structural levels, helps explain this health inequity. Yet, the relationship between racial discrimination and biological processes in the context of traumatic injury has yet to be fully explored. The current study examined whether racial discrimination is associated with a cumulative measure of biological stress, the gene expression profile conserved transcriptional response to adversity (CTRA), in Black trauma survivors. Two-weeks (T1) and six-months (T2) post-injury, Black participants (N = 94) provided a blood specimen and completed assessments of lifetime racial discrimination and PTSD symptoms. Mixed effect linear models evaluated the relationship between change in CTRA gene expression and racial discrimination while adjusting for age, gender, body mass index (BMI), smoking history, heavy alcohol use history, and trauma-related variables (mechanism of injury, lifetime trauma). Results revealed that for individuals exposed to higher levels of lifetime racial discrimination, CTRA significantly increased between T1 and T2. Conversely, CTRA did not increase significantly over time in individuals exposed to lower levels of lifetime racial discrimination. Thus, racial discrimination appeared to lead to a more sensitized biological profile which was further amplified by the effects of a recent traumatic injury. These findings replicate and extend previous research elucidating the processes by which racial discrimination targets biological systems.
Assuntos
Racismo , Transtornos de Estresse Pós-Traumáticos , Humanos , Centros de Traumatologia , População Negra/genética , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Expressão Gênica/genéticaRESUMO
Affective reactivity to stress is a person-level measurement of how well an individual copes with daily stressors. A common method of measuring affective reactivity entails the estimation of within-person differences of either positive or negative affect on days with and without stressors present. Individuals more reactive to common stressors, as evidenced by affective reactivity measurements, have been shown to have increased levels of circulating pro-inflammatory markers. While affective reactivity has previously been associated with inflammatory markers, the upstream mechanistic links underlying these associations are unknown. Using data from the Midlife in the United States (MIDUS) Refresher study (N = 195; 52% female; 84% white), we quantified daily stress processes over 10 days and determined individuals' positive and negative affective reactivities to stressors. We then examined affective reactivity association with peripheral blood mononuclear cell (PBMC) gene expression of the immune-related conserved transcriptional response to adversity. Results indicated that individuals with a greater decrease in positive affect to daily stressors exhibited heightened PBMC JUNB expression after Bonferroni corrections (p-adjusted < 0.05). JUNB encodes a protein that acts as a transcription factor which regulates many aspects of the immune response, including inflammation and cell proliferation. Due to its critical role in the activation of macrophages and maintenance of CD4+ T-cells during inflammation, JUNB may serve as a potential upstream mechanistic target for future studies of the connection between affective reactivity and inflammatory processes. Overall, our findings provide evidence that affective reactivity to stress is associated with levels of immune cell gene expression.
Assuntos
Leucócitos Mononucleares , Estresse Psicológico , Humanos , Feminino , Estados Unidos , Masculino , Estresse Psicológico/genética , Estresse Psicológico/psicologia , Inflamação/genética , Individualidade , Expressão Gênica/genética , Afeto/fisiologiaRESUMO
OBJECTIVE: Aging is associated with increased pro-inflammatory gene expression and systemic inflammation, and psychosocial stress may accelerate these changes. Mindfulness interventions show promise for reducing psychosocial stress and extending healthspan. Inflammatory pathways may play a role. In a sample of lonely older adults, we tested whether mindfulness training reduces proinflammatory gene expression and protein markers of systemic inflammation. METHODS: Lonely older adults (65-85 years; N = 190) were randomly assigned to an 8-week Mindfulness-Based Stress Reduction (MBSR) or matched Health Enhancement Program (HEP). Blood was drawn pre- and post-intervention and at 3-month follow-up. In peripheral blood mononuclear cells (PBMCs), RNA profiling was used to assess transcriptional regulation by pro-inflammatory NF-kB as well as ß-adrenergic CREB, antiviral IRF, and glucocorticoid receptor (GR) transcription factors. Plasma was assayed for proinflammatory markers IL-6 and CRP. Analyses tested time (pre, post, follow-up) by condition (MBSR versus HEP) effects. RESULTS: MBSR reduced NF-kB (d = .17, p = .028) but did not alter CREB (d = .10, p = .20), IRF (d = .13, p = .086), or GR activity (d = .14, p = .063) relative to HEP over time. Contrary to predictions, there were no time × condition effects of MBSR compared to HEP on reducing circulating IL-6 or CRP. CONCLUSIONS: In lonely older adults, MBSR reduced cellular pro-inflammatory gene regulation in ways that would predict reduced disease risk. However, no similar effect was observed for circulating protein markers of inflammation. These results provide specificity about how mindfulness interventions may impact distinct inflammatory markers among aging adults in ways that may have important implications for healthspan. TRIAL REGISTRATION: Clinical Trials identifier NCT02888600.
RESUMO
Achieving maximal health outcomes via health promotion and disease prevention requires the adoption of healthy behaviors. Brief action planning (BAP) is a method for patient self-management, health behavior change, and health coaching with potentially broad implications for and clinical applications in health and health care contexts. This scoping review presents 5 major findings about the literature on BAP: the principal geographic locations and the clinical contexts of its application, the types of research evaluations that it has undergone to date, the theoretic frameworks in which it is grounded, and the fidelity of its use in clinical practice.
Assuntos
Entrevista Motivacional , Humanos , Entrevista Motivacional/métodos , Atenção à SaúdeRESUMO
Disparities in socio-economic status (SES) predict many immune system-related diseases, and previous research documents relationships between SES and the immune cell transcriptome. Drawing on a bioinformatically-informed network approach, we situate these findings in a broader molecular framework by examining the upstream regulators of SES-associated transcriptional alterations. Data come from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative sample of 4,543 adults in the United States. Results reveal a network-of differentially-expressed genes, transcription factors, and protein neighbors of transcription factors- that shows widespread SES-related dysregulation of the immune system. Mediational models suggest that body mass index plays a key role in accounting for many of these associations. Overall, the results reveal the central role of upstream regulators in socioeconomic differences in the molecular basis of immunity, which propagate to increase risk of chronic health conditions in later-life.
RESUMO
This paper addresses women's empowerment in agriculture, innovations in its measurement, and emerging evidence. We discuss the evolution of the conceptualization and measurement of women's empowerment and gender equality since 2010. Using a gender and food systems framework and a standardized measure of women's empowerment, the Women's Empowerment in Agriculture Index (WEAI), we review the evidence on "what works" to empower women based on impact evaluations of a portfolio of 11 agricultural development projects with empowerment objectives and a scoping review of livestock interventions. We then review the evidence on associations between empowering women and societal benefits--agricultural productivity, incomes, and food security and nutrition. We conclude with recommendations for measurement and policy.
RESUMO
Background and objectives: A recent exploratory study of transcriptional effects of long-term practice of Transcendental Meditation (TM) technologies found evidence for altered expression of genes associated with health and disease. In the present secondary analysis of those data, we test the more specific hypothesis that this sample of long-term practitioners shows a significant reduction in markers of the "Conserved Transcriptional Response to Adversity" (CTRA), an RNA profile characterized by up-regulated inflammation and down-regulated Type I interferon (IFN) activity. Materials and methods: Data come from a previously published study providing genome-wide transcriptional profiles of peripheral blood mononuclear cells (PBMC) from healthy, 38-year practitioners of TM technologies and matched controls (n = 12, mean age 65). The current analysis specifically tests for differential expression of a previously established CTRA indicator gene score, with cross-validation by promoter-based bioinformatic analysis of CTRA-typical differences in transcription factor activity and monocyte subset cellular origins. Results: Compared to controls, the TM group showed lower expression of a pre-specified set of CTRA indicator genes. These effects were accompanied by genome-wide indications of down-regulated pro-inflammatory transcription factor activity (NF-κB, AP-1), up-regulated activity of Interferon Response Factors (IRF) and reduced transcriptional activity of classical monocytes. Conclusions: A sample of long-term practitioners of TM showed reduced CTRA gene expression in PBMC compared to matched controls, supporting the likely value of further research to evaluate causality and specificity of this potential mechanism of health benefits in meditators.
RESUMO
Diverse manifestations of biological aging often reflect disparities in socioeconomic status (SES). In this paper, we examine associations between indicators of SES and an mRNA-based aging signature during young adulthood, before clinical indications of aging are common. We use data from wave V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of adults aged 33-43 years, with transcriptomic data from a subset of 2,491 participants. Biological aging is measured using 1) a composite transcriptomic aging signature previously identified by Peters et al.'s out-of-sample meta-analysis (Nat Commun. 2015;6:8570) and 2) 9 subsets that represent functional pathways of coexpressed genes. SES refers to income, education, occupation, subjective social status, and a composite measure combining these 4 dimensions. We examine hypothesized mechanisms through which SES could affect aging: body mass index, smoking, health insurance status, difficulty paying bills, and psychosocial stress. We find that SES-especially the composite measure and income-is associated with transcriptomic aging and immune, mitochondrial, ribosomal, lysosomal, and proteomal pathways. Counterfactual mediational models suggest that the mediators partially account for these associations. The results thus reveal that numerous biological pathways associated with aging are already linked to SES in young adulthood.
Assuntos
Envelhecimento , Classe Social , Adulto , Adolescente , Humanos , Adulto Jovem , Estudos Longitudinais , Envelhecimento/genética , Fumar , Renda , Fatores SocioeconômicosRESUMO
BACKGROUND: Social connections are crucial to human health and well-being. Previous research on molecular mechanisms in health has focused primarily on the individual-level perception of social connections (e.g., loneliness). This study adopted socio-centric social network analysis that includes all social ties from the entire population of interest to examine the group-level social connections and their association with a molecular genomic measure of health. METHODS: Using socio-centric (global) social network data from an entire village in Korea, we investigated how social network characteristics are related to immune cell gene expression among older adults. Blood samples were collected (N = 53, 65-79 years) and mixed effect linear model analyses were performed to examine the association between social network characteristics and Conserved Transcriptional Response to Adversity (CTRA) RNA expression patterns. RESULTS: Social network positions measured by k-core score, the degree of cohesive core positions in an entire village, were significantly associated with CTRA downregulation. Such associations emerged above and beyond the effects of perceived social isolation (loneliness) and biobehavioral risk factors (smoking, alcohol, BMI, etc.). Social network size, defined as degree centrality, was also associated with reduced CTRA gene expression, but its association mimicked that of perceived social isolation (loneliness). CONCLUSIONS: The current findings implicate community-level social network characteristics in the regulation of individual human genome function above and beyond individual-level perceptions of connectedness.
Assuntos
População do Leste Asiático , Isolamento Social , Humanos , Idoso , Solidão , Regulação para Baixo , Rede Social , Apoio SocialRESUMO
The exciting field of human social genomics provides an evolutionarily informed, multilevel framework for understanding how positive and negative social-environmental experiences affect the genome to impact lifelong health, well-being, behavior, and longevity. In this review, we first summarize common patterns of socially influenced changes in the expression of pro-inflammatory and antiviral immune response genes (e.g., the Conserved Transcriptional Response to Adversity), and the multilevel psychological, neural, and cell signaling pathways by which social factors regulate human gene expression. Second, we examine how these effects are moderated by genetic polymorphisms and the specific types of social-environmental experiences that most strongly affect gene expression and health. Third, we identify positive psychosocial experiences and interventions that have been found to impact gene expression. Finally, we discuss promising opportunities for future research on this topic and how health care providers can use this information to improve patient health and well-being.