Material hardship and telomere length in children.

Telomere length (TL) serves as a biomarker of exposure to stressors, including material hardship. Data from the Future of Families and Child Wellbeing Study (1998-2015) were utilized to determine whether prior material hardship was associated with shorter salivary TL at years 9 and 15. 49% of the year 9 study population were female, 49% were Black, and 25% were Hispanic. At year 9 (N = 1990), regression analyses found a significant association between prior material hardship and shorter TL (ß = -.005, p < .01). Additionally, at year 15 (N = 1874), material hardship experienced during infancy and toddlerhood was associated with shorter TL (ß = -.009, p < .01), pointing toward infancy and toddlerhood as a sensitive period.

Taking John Schulenberg's "long view" on successful transitions to adulthood: Associations with adult substance use.

Can positive transitions into young adulthood at age 25 prevent problematic substance use at age 31, even in the context of childhood adverse family environments, conduct problems, and adolescent substance use? We lean on John Schulenberg's developmental framework to examine this question, focusing on the potential young adult milestones of high school and college graduation, employment, residential independence, romantic partnership, and parenthood. Data came from a prospective-longitudinal multi-method study with N = 1199 participants who were first assessed at age 5 years old and followed to age 31. An accumulation of positive transitions in young adulthood (age 25) was associated with lower likelihood of age 31 problematic cannabis use. The protective effect for problematic cannabis use remained even when adjusting for childhood adverse family environments and was primarily driven by successful college graduation and/or home ownership. The accumulation of positive transitions protected individuals at modest to somewhat elevated risk due to childhood adverse family environments from experiencing age 31 cannabis use problems. However, for other individuals with very high numbers of conduct problems, or with high levels of adolescent substance use, the protective effects of accumulated positive transitions to young adulthood were less strong or nonexistent. Moreover, individuals who completed college or obtained full-time employment by 25 were more likely to report problematic age 31 alcohol use. These findings highlight the central tenets of John Schulenberg's developmental framework, including the examination of ontogenetic continuity and discontinuity, the interplay of developmentally distal and proximal effects, and the identification of developmental protective factors that may sway people toward or away from substance use.

Institutional Context Shapes the Physical Health of College Graduates Differently for U.S. White, Black, and Hispanic Adults.

Greater educational attainment is generally associated with healthier and longer lives. However, important heterogeneity in who benefits from educational attainment, how much, and why remains underexplored. In particular, in the United States, the physical health returns to educational attainment are not as large for minoritized racial and ethnic groups compared with individuals racialized as White. Yet, our current understanding of ethnoracial differences in educational health disparities is limited by an almost exclusive focus on the quantity of education attained without sufficient attention to heterogeneity within educational attainment categories, such as different institution types among college graduates. Using biomarker data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we test whether the physical health of college graduates in early adulthood (aged 24-32) varies by institution type and for White, Black, and Hispanic adults. In considering the role of the college context, we conceptualize postsecondary institutions as horizontally stratified and racialized institutional spaces with different implications for the health of their graduates. Finally, we quantify the role of differential attendance at and returns to postsecondary institution type in shaping ethnoracialized health disparities among college graduates in early adulthood.

The Sociodemographic and Lifestyle Correlates of Epigenetic Aging in a Nationally Representative U.S. Study of Younger Adults.

Importance: Epigenetic clocks represent molecular evidence of disease risk and aging processes and have been used to identify how social and lifestyle characteristics are associated with accelerated biological aging. However, most of this research is based on older adult samples who already have measurable chronic disease. Objective: To investigate whether and how sociodemographic and lifestyle characteristics are related to biological aging in a younger adult sample across a wide array of epigenetic clock measures. Design: Nationally representative prospective cohort study. Setting: United States (U.S.). Participants: Data come from the National Longitudinal Study of Adolescent to Adult Health, a national cohort of adolescents in grades 7-12 in U.S. in 1994 followed for 25 years over five interview waves. Our analytic sample includes participants followed-up through Wave V in 2016-18 who provided blood samples for DNA methylation (DNAm) testing (n=4237) at Wave V. Exposure: Sociodemographic (sex, race/ethnicity, immigrant status, socioeconomic status, geographic location) and lifestyle (obesity status, exercise, tobacco, and alcohol use) characteristics. Main Outcome: Biological aging assessed from blood DNAm using 16 epigenetic clocks when the cohort was aged 33-44 in Wave V. Results: While there is considerable variation in the mean and distribution of epigenetic clock estimates and in the correlations among the clocks, we found sociodemographic and lifestyle factors are more often associated with biological aging in clocks trained to predict current or dynamic phenotypes (e.g., PhenoAge, GrimAge and DunedinPACE) as opposed to clocks trained to predict chronological age alone (e.g., Horvath). Consistent and strong associations of faster biological aging were found for those with lower levels of education and income, and those with severe obesity, no weekly exercise, and tobacco use. Conclusions and Relevance: Our study found important social and lifestyle factors associated with biological aging in a nationally representative cohort of younger-aged adults. These findings indicate that molecular processes underlying disease risk can be identified in adults entering midlife before disease is manifest and represent useful targets for interventions to reduce social inequalities in heathy aging and longevity. Key Points: Question: Are epigenetic clocks, measures of biological aging developed mainly on older-adult samples, meaningful for younger adults and associated with sociodemographic and lifestyle characteristics in expected patterns found in prior aging research?Findings: Sociodemographic and lifestyle factors were associated with biological aging in clocks trained to predict morbidity and mortality showing accelerated aging among those with lower levels of education and income, and those with severe obesity, no weekly exercise, and tobacco use.Meaning: Age-related molecular processes can be identified in younger-aged adults before disease manifests and represent potential interventions to reduce social inequalities in heathy aging and longevity.

Structural racism in primary schools and changes in epigenetic age acceleration among Black and White youth.

Structural racism generates racial inequities in U.S. primary education, including segregated schools, inequitable funding and resources, racial disparities in discipline and achievement, and hostile racial climates, which are risk factors for adverse youth health and development. Black youth are disproportionately exposed to adverse school contexts that may become biologically embedded via stress-mediated epigenetic pathways. This study examined whether childhood exposure to adverse school contexts is associated with changes in epigenetic aging during adolescent development. DNA methylation-based epigenetic clocks were calculated from saliva samples at ages 9 and 15 among Black (n = 774) and White (n = 287) youth in the Future of Families and Child Wellbeing Study (2009-2015). We performed latent class analyses to identify race-specific primary school contexts using administrative data on segregation, discipline, achievement, resources, economic disadvantage, and racial harassment. We then estimated change in epigenetic age acceleration from childhood to adolescence across school typologies using GrimAge, PhenoAge, and DunedinPACE epigenetic clocks. Three distinct school contexts were identified for Black youth: segregated and highly-disadvantaged (17.0%), segregated and moderately-disadvantaged (52.1%), and integrated and moderately-disadvantaged (30.8%). Two school contexts emerged for White youth: integrated and unequal (46.5%) and predominantly White & advantaged (53.5%). At age 15, Black youth who attended segregated and highly-disadvantaged primary schools experienced increases in their speed of epigenetic aging with GrimAge and DunedinPACE. Slowed epigenetic aging with GrimAge was observed for Black youth who attended integrated and moderately-disadvantaged schools. School contexts were not associated with changes in epigenetic age acceleration for White youth. Our findings suggest that manifestations of structural racism in primary school contexts are associated with early-life epigenetic age acceleration and may forecast future health inequities.

Socioeconomic Inequalities and Molecular Risk for Aging in Young Adulthood.

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.

Defining despair: Assessing the multidimensionality of despair and its association with suicidality and substance use in early to middle adulthood.

Despite considerable scientific interest in documenting growing despair among U.S. adults, far less attention has been paid to defining despair and identifying appropriate measures. Emerging perspectives from social science and psychiatry outline a comprehensive, multidimensional view of despair, inclusive of individuals' cognitive, emotional, biological and somatic, and behavioral circumstances. The current study assesses the structure and plausibility of this framework based on longitudinal data spanning early to middle adulthood. We identified 40 measures of different dimensions of despair in Wave IV (2008-2009) of the National Longitudinal Study of Adult to Adolescent Health (n = 9149). We used structural equation modeling to evaluate hypothesized relationships among observed and latent variables; we then regressed Wave V (2016-2018) suicidality, heavy drinking, marijuana use, prescription drug misuse, and illicit drug use on latent despair. Our analyses find that models for separate dimensions of despair and overall despair demonstrated excellent fit. Overall despair was a significant predictor of Wave V outcomes, especially suicidality, accounting for 20% of its variation, as compared to 1%-7% of the variation in substance use. Suicidality was consistently associated with all domains of despair; behavioral despair explained the most variation in substance use. Given these results we contend that, lacking direct measures, latent despair can be modeled using available survey items; however, some items are likely better indicators of latent dimensions of despair than others. Moreover, the association between despair and key health behaviors varies considerably, challenging its status as a mechanism simultaneously underlying increased substance use and suicide mortality in the United States. Critically, further validation of measures in other surveys can improve the operationalization of despair and its associated conceptual and theoretical frameworks, thus advancing our understanding of this concept.

Midlife Health in Britain and the US: A comparison of Two Nationally Representative Cohorts.

Background: Older adults in the United States (US) have worse health and wider socioeconomic inequalities in health compared to Britain. Less is known about how health in the two countries compares in midlife, a time of emerging health decline, including inequalities in health. Methods: We compare measures of smoking status, alcohol consumption, obesity, self-rated health, cholesterol, blood pressure, and glycated haemoglobin using population-weighted modified Poisson regression in the 1970 British Cohort Study (BCS70) in Britain (N= 9,665) and the National Longitudinal Study of Adolescent to Adult Health (Add Health) in the US (N=12,297), when cohort members were aged 34-46 and 33-43, respectively. We test whether associations vary by early- and mid-life socioeconomic position. Findings: US adults had higher levels of obesity, high blood pressure and high cholesterol. Prevalence of poor self-rated health, heavy drinking, and smoking was worse in Britain. We found smaller socioeconomic inequalities in midlife health in Britain compared to the US. For some outcomes (e.g., smoking), the most socioeconomically advantaged group in the US was healthier than the equivalent group in Britain. For other outcomes (hypertension and cholesterol), the most advantaged US group fared equal to or worse than the most disadvantaged groups in Britain. Interpretation: US adults have worse cardiometabolic health than British counterparts, even in early midlife. The smaller socioeconomic inequalities and better overall health in Britain may reflect differences in access to health care, welfare systems, or other environmental risk factors. Funding: ESRC, UKRI, MRC, NIH, European Research Council, Leverhulme Trust.

Socioeconomic inequalities in molecular risk for chronic diseases observed in young adulthood.

Many common chronic diseases of aging are negatively associated with socioeconomic status (SES). This study examines whether inequalities can already be observed in the molecular underpinnings of such diseases in the 30s, before many of them become prevalent. Data come from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a large, nationally representative sample of US subjects who were followed for over two decades beginning in adolescence. We now have transcriptomic data (mRNA-seq) from a random subset of 4,543 of these young adults. SES in the household-of-origin and in young adulthood were examined as covariates of a priori-defined mRNA-based disease signatures and of specific gene transcripts identified de novo. An SES composite from young adulthood predicted many disease signatures, as did income and subjective status. Analyses highlighted SES-based inequalities in immune, inflammatory, ribosomal, and metabolic pathways, several of which play central roles in senescence. Many genes are also involved in transcription, translation, and diverse signaling mechanisms. Average causal-mediated effect models suggest that body mass index plays a key role in accounting for these relationships. Overall, the results reveal inequalities in molecular risk factors for chronic diseases often decades before diagnoses and suggest future directions for social signal transduction models that trace how social circumstances regulate the human genome.

Long-term Outcomes of Childhood Family Income Supplements on Adult Functioning.

Importance: During an ongoing longitudinal cohort study, a casino opening created a natural cash transfer experiment. Some participating families received income supplements, and others did not. The children in this study are now adults. Objective: To assess the long-term outcomes of family income supplements received in childhood. Design, Setting, and Participants: This community-representative longitudinal cohort study set in western North Carolina assessed 1266 participants aged 9, 11, and 13 years at intake up to 11 times up to age 30 years from January 1993 to December 2015. Data were analyzed from January to December 2021. Exposures: In 1996, a southeastern American Indian tribe implemented a cash transfer program of approximately $5000 annually per person for tribal members. Participants were compared on whether their family ever received the cash transfers (American Indian vs non-American Indian), the duration of the transfers, and annual amount based on the number of parents. Main Outcomes and Measures: Participants were followed up at ages 25 and 30 years to assess mental health symptoms, substance use symptoms, and functional outcomes (physical health, risky or illegal behaviors, and financial and social functioning). Results: Of 1266 included participants, 320 (25.3%) were American Indian and 581 (49.7%) were female. Participants whose families received cash transfers during childhood reported fewer anxiety symptoms (relative risk [RR], 0.33; 95% CI, 0.25-0.44), depressive symptoms (RR, 0.51; 95% CI, 0.42-0.62), and cannabis symptoms (RR, 0.47; 95% CI, 0.27-0.82). They also reported improved physical health (RR, 0.66; 95% CI, 0.55-0.80) and financial functioning (RR, 0.78; 95% CI, 0.67-0.89) and fewer risky or illegal behaviors (RR, 0.57; 95% CI, 0.46-0.72) compared with those who did not receive the cash transfer. This pattern was supported by a series of heterogeneity analyses in which children whose families received the transfers for the longest duration and whose families received the largest transfer (due to having multiple American Indian parents) had the lowest levels of symptoms and the highest levels of functioning. Conclusions and Relevance: In this natural experiment, a family cash transfer in childhood was associated with positive adult functioning 20 years later. The findings support programs like the child tax credit or universal basic income that provide cash directly to families with children.

Contextualizing Educational Disparities in Health: Variations by Race/Ethnicity, Nativity, and County-Level Characteristics.

Educational disparities in health are well documented, yet the education-health relationship is inconsistent across racial/ethnic and nativity groups. These inconsistencies may arise from characteristics of the early life environments in which individuals attain their education. We evaluate this possibility by investigating (1) whether educational disparities in cardiometabolic risk vary by race/ethnicity and nativity among Black, Hispanic, and White young adults; (2) the extent to which racial/ethnic-nativity differences in the education-health relationship are contingent on economic, policy, and social characteristics of counties of early life residence; and (3) the county characteristics associated with the best health at higher levels of education for each racial/ethnic-nativity group. Using data from the National Longitudinal Study of Adolescent to Adult Health, we find that Black young adults who achieve high levels of education exhibit worse health across a majority of contexts relative to their White and Hispanic counterparts. Additionally, we observe more favorable health at higher levels of education across almost all contexts for White individuals. For all other racial/ethnic-nativity groups, the relationship between education and health depends on the characteristics of the early life counties of residence. Findings highlight place-based factors that may contribute to the development of racial/ethnic and nativity differences in the education-health relationship among U.S. young adults.

The Early Life Course of Body Weight and Gene Expression Signatures for Disease.

We examined the way body-weight patterns through the first 4 decades of life relate to gene expression signatures of common forms of morbidity, including cardiovascular disease (CVD), type 2 diabetes (T2D), and inflammation. As part of wave V of the nationally representative National Longitudinal Study of Adolescent to Adult Health (1997-2018) in the United States, mRNA abundance data were collected from peripheral blood (n = 1,132). We used a Bayesian modeling strategy to examine the relative associations between body size at 5 life stages-birth, adolescence, early adulthood, young adulthood, and adulthood-and gene expression-based disease signatures. We compared life-course models that consider critical or sensitive periods, as well as accumulation over the entire period. Our results are consistent with a sensitive-period model when examining CVD and T2D gene expression signatures: Birth weight has a prominent role for the CVD and T2D signatures (explaining 33.1% and 22.1%, respectively, of the total association accounted for by body size), while the most recent adult obesity status (ages 33-39) is important for both of these gene expression signatures (24.3% and 35.1%, respectively). Body size in all life stages was associated with inflammation, consistent with the accumulation model.

Is educational attainment associated with young adult cardiometabolic health?

Educational disparities in health and mortality are well-documented and evidence suggests that they may be widening. Yet, there is much unknown about when educational disparities begin to emerge and for whom. This paper investigates the association between educational attainment and cardiometabolic health in young adults with critical attention paid to differences across racial/ethnic and sex subgroups. We focus on cardiometabolic health in young adulthood as it is particularly relevant for understanding current population health trends. We used data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) when participants were aged 12-19 years (Wave I) and aged 24-32 years (Wave IV). Using a series of logistic regression models, we first estimated the association between education and five markers of cardiometabolic health (high-risk blood pressure, high-risk waist circumference, diabetes/pre-diabetes, hyperlipidemia, and high-risk inflammation). We then examined the extent to which this association was explained by adolescent health and both adolescent and young adult socioeconomic status (SES) (including parental education, participant educational attainment, household income, and employment status). Finally, we investigated whether the association between educational attainment and cardiometabolic health differed by race/ethnicity and sex. We found evidence of an association between educational attainment and cardiometabolic health that persisted net of adolescent health, adolescent SES, and young adult SES. We also found some evidence of modest differences in this association by race/ethnicity and sex. Our findings suggest that even as early as young adulthood there are disparities in cardiometabolic health by educational attainment, which may lead to even larger disparities in late life health.

Youth academic achievement, social context, and body mass index.

This study assesses the relationship between academic achievement and body mass index for age (BMI) trajectories across childhood and adolescence, and investigates how this relationship is moderated by social context. Specifically, we test the hypothesis that academic achievement is not associated with improved BMI among youth from disadvantaged social contexts. We test for differences by race/ethnicity, and examine the role of county-level economic mobility in shaping these patterns. We use data from the longitudinal Fragile Families and Child Wellbeing Study (FFCWS), an ongoing birth cohort study representative of children born in large US cities in 2000, and measure BMI, academic achievement, and social context at Years 5, 9, and 15. Estimating multilevel random effects linear regression models of BMI from childhood to adolescence, we find that youth who were exposed to social advantage displayed a negative association between academic achievement and BMI. In contrast, youth exposed to social disadvantage displayed no association between academic achievement and BMI. This difference was observed regardless of race/ethnicity. County-level economic mobility modified the observed relationship, such that youth living in places with low levels of mobility displayed higher BMI associated with high academic performance. The results suggest that the health costs of academic achievement among disadvantaged youth are concentrated in areas with low institutional support for upward mobility. The findings demonstrate that the unequal benefits of educational attainment begin early in life, while living in places that promote upward mobility can help individuals realize the health benefits of their own educational attainment.

Prevalence and Childhood Precursors of Opioid Use in the Early Decades of Life.

Importance: Opioid use disorder and opioid deaths have increased dramatically in young adults in the US, but the age-related course or precursors to opioid use among young people are not fully understood. Objective: To document age-related changes in opioid use and study the childhood antecedents of opioid use by age 30 years in 6 domains of childhood risk: sociodemographic characteristics; school or peer problems; parental mental illness, drug problems, or legal involvement; substance use; psychiatric illness; and physical health. Design, Setting, and Participants: This community-representative prospective longitudinal cohort study assessed 1252 non-Hispanic White individuals and American Indian individuals in rural counties in the central Appalachia region of North Carolina from January 1993 to December 2015. Data were analyzed from January 2019 to January 2020. Exposures: Between ages 9 and 16 years, participants and their parents were interviewed up to 7 times using the Child and Adolescent Psychiatric Assessment and reported risk factors in 6 risk domains. Main Outcomes and Measures: Participants were assessed again at ages 19, 21, 25, and 30 years for nonheroin opioid use (any and weekly) and heroin use using the structured Young Adult Psychiatric Assessment. Results: Of 1252 participants, 342 (27%) were American Indian. By age 30 years, 322 participants had used a nonheroin opioid (24.2%; 95% CI, 21.8-26.5), 155 had used a nonheroin opioid weekly (8.8%; 95% CI, 7.2-10.3), and 95 had used heroin (6.6%; 95% CI, 5.2-7.9). Childhood risk markers for later opioid use included male sex, tobacco use, depression, conduct disorder, cannabis use, having peers exhibiting social deviance, parents with legal involvement, and elevated systemic inflammation. In final models, childhood tobacco use, depression, and cannabis use were most robustly associated with opioid use in young adulthood (ages 19 to 30 years). Chronic depression and dysthymia were strongly associated with any nonheroin opioid use (OR. 5.43; 95% CI, 2.35-12.55 and OR, 7.13; 95% CI, 1.99-25.60, respectively) and with weekly nonheroin opioid use (OR, 8.89; 95% CI, 3.61-21.93 and OR, 11.51; 95% CI, 3.05-42.72, respectively). Among young adults with opioid use, those with heroin use had the highest rates of childhood psychiatric disorders and comorbidities. Conclusions and Relevance: Childhood tobacco use and chronic depression may be associated with impaired reward system functioning, which may increase young adults' vulnerability to opioid-associated euphoria. Preventing and treating early substance use and childhood mental illness may help prevent later opioid use.

Protocol - Evaluating the Effect of ACA Medicaid Expansion on Mortality During the COVID-19 Pandemic Using County-level Matching.

States are able to choose whether to expand Medicaid as part of the Affordable Care Act (ACA); thus it is of interest to understand the impact of this policy choice. In this protocol, we outline a study on the impact of Medicaid expansion as part of the ACA on mortality during the COVID-19 pandemic in the United States. County-level matching using full, optimal matching with a propensity score model is used to estimate causal effects in this observational study. Due to the provisional nature of mortality data in 2020 as reported by the CDC, we outline a modified aligned rank test to account for censored data as well as reporting lags for different states. We aim to make connections between statistical and ethnographic methodologies by particularly examining adjacent counties and similar counties that are in the same region of the US and in vastly different regions of the US. Finally, we aim to add to the growing literature about the effect of ACA Medicaid expansion on mortality by calculating effects, disaggregating by race.

Associations of Despair With Suicidality and Substance Misuse Among Young Adults.

Importance: Deaths of despair is a term that has recently been used to describe the increases in premature mortality from suicides, drug overdoses (particularly from opiates), and alcohol-related liver disease among US adults. Despite the use of the term despair, its role in these causes of premature death has not been empirically tested. Objective: To test whether despair among young adults is associated with suicidal thoughts and behavior, alcohol misuse, and drug misuse. Design, Setting, and Participants: The Great Smoky Mountains Study is a Southeastern, mixed urban-rural population-based cohort study conducted from November 10, 1992, to September 22, 2015. A total of 1420 participants originally 9, 11, and 13 years of age were followed up 11 times to 30 years of age (11 230 person-observations). A total of 1154 of 1400 living participants (82.4%) were assessed at 30 years of age. Statistical analysis was performed from May 7, 2019, to April 10, 2020. Exposures: Participants were assessed with structured interviews for indicators of despair (eg, hopelessness, helplessness, low self-worth, and feeling unloved). Despair was assessed with items from structured interviews: the Child and Adolescent Psychiatric Assessment and the Young Adult Psychiatric Assessment. Main Outcomes and Measures: Structured interviews were used to assess suicidal thoughts and behavior, substance use, and Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) alcohol use disorder and drug use disorder (including opioids) in young adulthood (2424 observations of 1266 individuals between 25 and 30 years of age). Results: This study included 1420 individuals (790 male individuals). During young adulthood (25 and 30 years of age), the 3-month weighted prevalence of any despair was 19.5% (476 of 2424 observations) with 7.6% of participants (201 of 2424 observations) reporting 2 or more despair items. In longitudinal, lagged models, despair scores (range, 0-3) were associated with more suicidal thoughts and behaviors (odds ratio [OR], 1.5; 95% CI, 1.1-2.0), illicit drug use (OR, 1.7; 95% CI, 1.2-2.5), and opioid use (OR, 1.9; 95% CI, 1.1-3.3) but not alcohol use disorder (OR, 0.8; 95% CI, 0.6-1.2). These associations persisted after accounting for sociodemographic factors (eg, poverty and educational level), lagged outcome status, and lagged depression status. The associations between despair and study outcomes were stronger in models accounting for long-term measures of despair extending back to childhood. There was no consistent pattern of moderation by sociodemographic factors. Conclusions and Relevance: This study's findings suggest an empirical basis for longitudinal associations between despair and several, but not all, precursors of "deaths of despair" in rural Appalachia. Individual despair should be studied as a potential factor associated with morbidity and impairment in young adulthood.

Early Signs of Gut Microbiome Aging: Biomarkers of Inflammation, Metabolism, and Macromolecular Damage in Young Adulthood.

Emerging links between gut microbiota and diseases of aging point to possible shared immune, metabolic, and cellular damage mechanisms, operating long before diseases manifest. We conducted 16S rRNA sequencing of fecal samples collected from a subsample (n = 668) of Add Health Wave V, a nationally representative longitudinal study of adults aged 32-42. An overlapping subsample (n = 345) included whole-blood RNA-seq. We examined associations between fecal taxonomic abundances and dried blood spot-based markers of lipid and glucose homeostasis and C-reactive protein (measured in Wave IV), as well as gene expression markers of inflammation, cellular damage, immune cell composition, and transcriptomic age (measured in Wave V), using Bayesian hierarchical models adjusted for potential confounders. We additionally estimated a co-abundance network between inflammation-related genes and bacterial taxa using penalized Gaussian graphical models. Strong and consistent microbiota associations emerged for HbA1c, glucose, C-reactive protein, and principal components of genes upregulated in inflammation, DNA repair, and reactive oxygen species, with Streptococcus infantis, Pseudomonas spp., and Peptoniphilus as major players for each. This pattern was largely echoed (though attenuated) for immunological cell composition gene sets, and only Serratia varied meaningfully by transcriptomic age. Network co-abundance indicated relationships between Prevotella sp., Bacteroides sp., and Ruminococcus sp. and gut immune/metabolic regulatory activity, and Ruminococcus sp, Dialister, and Butyrivibrio crossotus with balance between Th1 and Th2 inflammation. In conclusion, many common associations between microbiota and major physiologic aging mechanisms are evident in early-mid adulthood and suggest avenues for early detection and prevention of accelerated aging.

Social determinants of health and survival in humans and other animals.

The social environment, both in early life and adulthood, is one of the strongest predictors of morbidity and mortality risk in humans. Evidence from long-term studies of other social mammals indicates that this relationship is similar across many species. In addition, experimental studies show that social interactions can causally alter animal physiology, disease risk, and life span itself. These findings highlight the importance of the social environment to health and mortality as well as Darwinian fitness-outcomes of interest to social scientists and biologists alike. They thus emphasize the utility of cross-species analysis for understanding the predictors of, and mechanisms underlying, social gradients in health.