Neighborhood disadvantage is associated with biological aging: Intervention-induced enhancement of couple functioning confers resilience.

The accelerated pace of biological aging predicts mortality and morbidity later in life. The current study examines whether a change in supportive couple functioning buffers accelerated aging associated with stressful community environments among Black Americans who live in rural, Southern, disadvantaged neighborhoods. We examined 348 Black American middle-aged adults assigned randomly to receive the Protecting Strong African American Families (ProSAAF) intervention or a control condition. The program was designed to enhance supportive couple functioning among Black Americans. We used DunedinPoAm to quantify the methylation pace of aging and employed the Area Deprivation Index at the census block group level to measure neighborhood disadvantage. Neighborhood disadvantage was associated with the accelerated pace of aging. Further, participation in ProSAAF enhanced supportive couple functioning, and improvement in couple functioning protected participants from the harmful effects of neighborhood disadvantage on the accelerated pace of aging. These findings supported mediated moderation and suggested that family-based prevention programs that enhance couple support may decrease the erosive effects of neighborhood disadvantage and improve prospects for healthy aging among rural, Southern, Black Americans living in difficult circumstances. This may provide a supplemental strategy for decreasing health disparities due to neighborhood disadvantage by enhancing family systems.

Shifts in lifestyle and socioeconomic circumstances predict change-for better or worse-in speed of epigenetic aging: A study of middle-aged black women.

BACKGROUND: While numerous studies have documented the power of new generation epigenetic clocks to predict morbidity and mortality, research regarding the causes of variation in speed of epigenetic aging is in the early stages. To the extent that these epigenetic clocks are robust measures of biological aging, they should be sensitive to various nutritional, behavioral, ecological, and social factors that have been shown to affect health. OBJECTIVE: Investigate over an 11-year period the extent to which changes in socioeconomic stress and lifestyle predict changes in speed of epigenetic aging among a sample of middle-aged African American women. METHODS: Using data from the Family and Community Health Study, we investigated whether changes in socioeconomic stress, diet, smoking, exercise, alcohol consumption, and relationship status predict changes in speed of biological aging assessed with 3 s-generation epigenetic clocks: AccelGrimAge, DunedinPoAm, and AccelPhenoAge. The study was able to avoid the challenges associated with self-reports of diet and smoking by employing recently developed epigenetic measures. RESULTS: Changes in socioeconomic stress and diet were associated with changes in speed of biological aging as assessed by all three epigenetic clocks, and changes in smoking was related to changes in AccelGrimAge and DunedinPoAm. Analyses controlling for cell-type indicated that in large measure diet exerts its effect on aging through its impact on the immune system. CONCLUSIONS: These findings suggest that adoption of a healthy diet and reduction in the use of tobacco are related to a decrease in epigenetic aging, whereas increased pressure relating to income, housing and economic independence are associated with an increase in the speed of aging. These effects were especially strong for the two epigenetic clocks AccelGrimAge and DunedinPoAm. Overall, the results indicate that stress and lifestyle changes may, for better or worse, influence the "biological weathering" often experienced by middle-aged African American women.

Relationship intervention indirectly buffers financial strain's effect on biological aging among Black adults.

Black adults in the rural South experience elevated financial strain and other contextual stressors, increasing their risk for poor health. Supportive relationships, particularly positive romantic relationships, have been shown to offset these risks. The present study aims to provide experimental evidence of the buffering effect of supportive relationships by testing whether participation in a relationship enhancement program (ProSAAF) that improves couple functioning (Barton, Beach, Wells, et al., 2018) subsequently buffers the effect of cumulative financial strain on biological aging (weathering). Postintervention financial strain was assessed four times. Deoxyribonucleic acid (DNA) was extracted from peripheral whole blood collected 6 years after baseline (n = 348 individuals), and patterns of methylation were used to index accelerated pace of aging. Couple functioning was treated as a latent construct comprising four self-report indicators: effective communication, relationship confidence, relationship satisfaction, and perceived partner support. Results indicated that cumulative financial strain was associated with accelerated pace of aging with a medium to large effect size. This effect was moderated by change in couple functioning such that individuals with greater improvement in couple functioning showed less epigenetic aging in response to cumulative financial strain. Additionally, there was a significant indirect buffering effect of ProSAAF on the association between cumulative financial strain and accelerated pace of aging. This is the first study to demonstrate that a couple-focused preventive intervention can reduce the impact of financial strain on rate of aging by enhancing couple functioning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neighborhood structural disadvantage and biological aging in a sample of Black middle age and young adults.

OBJECTIVES: Research on the social determinants of health has suggested that neighborhood disadvantage may undermine healthy aging and is particularly relevant for understanding health disparities. Recently, this work has examined deoxyribonucleic acid methylation (DNAm)-based measures of biological aging to understand the risk factors for morbidity and mortality. However, it is unknown whether neighborhood disadvantage is related to different indices of DNAm-based aging among Black Americans and whether such neighborhood effects vary as a function of age or gender. METHODS: Our analyses of a Black American sample included 448 young adults and 493 middle-aged adults. We measured neighborhood disadvantage using the Area Deprivation Index at the census block group level. DNAm-based accelerated aging indices were measured using established procedures. Regressions with clustered standard errors were used for the analysis. RESULTS: Neighborhood disadvantage was independently associated with acceleration in PhenoAge, GrimAge, and DunedinPoAm, among young and middle-aged adults. Further, there was no evidence that gender conditioned the effects of neighborhood disadvantage on the aging indices. CONCLUSIONS: Regardless of age groups or gender, accelerated biological aging among Black Americans is partly rooted in differences in neighborhood disadvantage. From a policy standpoint, our findings suggest that programs that decrease neighborhood disadvantage are likely to increase healthy aging, especially among Black Americans.

Re(Setting) Epigenetic Clocks: An Important Avenue Whereby Social Conditions Become Biologically Embedded across the Life Course.

Research on biological embedding of the social environment has been expedited by increased availability of biomarkers. Recently, this arsenal of measures has been expanded to include epigenetic clocks that indicate in years the extent to which an individual is older or younger than their chronological age. These measures of biological aging, especially GrimAge, are robust predictors of both illness and time to death. Importantly for sociologists, several studies have linked social conditions to these indices of aging. The present study extends this research using longitudinal data from a sample of 223 black women participating in the Family and Community Health Study. We find that changes in income and living arrangements over an 11-year period predict changes in speed of biological aging. These results provide further support for the idea that epigenetic aging is a mechanism whereby social conditions become biologically embedded. The utility of epigenetic clocks for sociological studies of health are discussed.

The Association between Neighborhood Disorder and Health: Exploring the Moderating Role of Genotype and Marriage.

The present study extends prior research on the link between neighborhood disorder and health by testing an integrated model that combines various social and biological factors. Hypotheses were tested using a sample of 325 African American women from the Family and Community Health Study (FACHS). As expected, inflammatory burden was the biophysiological mechanism that mediated much of the association between neighborhood physical disorder and perceived physical health. This finding provided additional support for the view that global self-ratings of health are powerful predictors of morbidity because, in large measure, they are indicators of chronic, systemic inflammation. Further, both genetic variation and marital status served to moderate the association between neighborhood disorder and health. Finally, being married largely eliminated the probability that neighborhood disorder would combine with genetic vulnerability to increase inflammatory burden and perceived illness. Overall, the findings demonstrate the value of constructing integrated models that specify various biophysiological mechanisms that link social conditions to physical health.

Racial Discrimination, Inflammation, and Chronic Illness Among African American Women at Midlife: Support for the Weathering Perspective.

It is widely accepted that socioeconomic status (SES) is a fundamental cause of health inequality. There is evidence, however, that race is also a fundamental cause of disparities in health. Based on this idea, the weathering hypothesis developed by Geronimus and her colleagues views the elevated rates of illness and disability seen among Black Americans as a physiological response to the structural barriers, daily slights, and other threats to identity that comprise the Black experience. The current study tests the weathering hypothesis using chronic inflammation as an indicator of biological weathering. Specifically, we examine the extent to which persistent exposure to racial discrimination predicts elevated inflammation and, in turn, diagnosed chronic illness, after taking into account SES and several control variables. This mediation model was tested using zero-inflated Poisson path modeling with five waves of data collected from 391 African American women participating in the Family and Community Health Study (FACHS). A 13-item index was used to assess exposure to racial discrimination across 8 years. ELISA blood assays of seven cytokines central to the inflammatory response were used to construct an inflammatory index. Respondents reported their diagnosed chronic diseases. Consonant with the weathering hypothesis, persistent exposure to discrimination predicted inflammation which, in turn, predicted number of chronic diseases. This indirect effect was statistically significant. SES predicted having a chronic disease and the various controls showed no effect. The findings support the idea that race, like SES, is a fundamental cause of health inequalities.

Childhood adversity is linked to adult health among African Americans via adolescent weight gain and effects are genetically moderated.

Identifying the mechanisms linking early experiences, genetic risk factors, and their interaction with later health consequences is central to the development of preventive interventions and identifying potential boundary conditions for their efficacy. In the current investigation of 412 African American adolescents followed across a 20-year period, we examined change in body mass index (BMI) across adolescence as one possible mechanism linking childhood adversity and adult health. We found associations of childhood adversity with objective indicators of young adult health, including a cardiometabolic risk index, a methylomic aging index, and a count of chronic health conditions. Childhood adversities were associated with objective indicators indirectly through their association with gains in BMI across adolescence and early adulthood. We also found evidence of an association of genetic risk with weight gain across adolescence and young adult health, as well as genetic moderation of childhood adversity's effect on gains in BMI, resulting in moderated mediation. These patterns indicated that genetic risk moderated the indirect pathways from childhood adversity to young adult health outcomes and childhood adversity moderated the indirect pathways from genetic risk to young adult health outcomes through effects on weight gain during adolescence and early adulthood.

The effects of social adversity, discrimination, and health risk behaviors on the accelerated aging of African Americans: Further support for the weathering hypothesis.

BACKGROUND: The weathering hypothesis views the elevated rates of illness, disability, and mortality seen among Black Americans as a physiological response to the structural barriers, material hardships, and identity threats that comprise the Black experience. While granting that lifestyle may have some significance, the fundamental explanation for heath inequalities is seen as race-related stressors that accelerate biological aging. OBJECTIVE: The present study tests the weathering hypothesis by examining the impact on accelerated aging of four types of adversity frequently experienced by Black Americans. Further, we investigate whether health risk behaviors mediate the effect of these conditions. METHOD: Our analyses utilize data from 494 middle-age, African American men and women participating in the Family and Community Healthy Study. The newly developed GrimAge index of accelerated aging is used as an indicator of weathering. Education, income, neighborhood disadvantage, and discrimination serve as the independent variables. Three health risk behaviors - diet, exercise, and alcohol consumption - are included as potential mediators of the four types of adversity. Marital status and gender are entered as controls. RESULTS: Multivariate analyses indicated that the four types of adversity predicted acceleration whereas marriage predicted deceleration in speed of aging. Males showed greater accelerated aging than females, but there was no evidence that gender conditioned the effect of adversity. The health risk behaviors were unrelated to accelerated aging and did not mediate the effect of the stressors. CONCLUSION: Modern medicine's emphasis on life style as the primary explanation for race-based health disparities ignores the way race-related adversity rooted in structural and cultural conditions serves to accelerate biological decline, thereby increasing risk of early onset of illness and death. Importantly, these social conditions can only be addressed through social policies and programs that target institutional racism and promote economic equity.

Array-Based Epigenetic Aging Indices May Be Racially Biased.

Epigenetic aging (EA) indices are frequently used as predictors of mortality and other important health outcomes. However, each of the commonly used array-based indices has significant heritable components which could tag ethnicity and potentially confound comparisons across racial and ethnic groups. To determine if this was possible, we examined the relationship of DNA methylation in cord blood from 203 newborns (112 African American (AA) and 91 White) at the 513 probes from the Levine PhenoAge Epigenetic Aging index to ethnicity. Then, we examined all sites significantly associated with race in the newborn sample to determine if they were also associated with an index of ethnic genetic heritage in a cohort of 505 AA adults. After Bonferroni correction, methylation at 50 CpG sites was significantly associated with ethnicity in the newborn cohort. The five most significant sites predicted ancestry with a receiver operator characteristic area under the curve of 0.97. Examination of the top 50 sites in the AA adult cohort showed that methylation status at 11 of those sites was also associated with percentage European ancestry. We conclude that the Levine PhenoAge Index is influenced by cryptic ethnic-specific genetic influences. This influence may extend to similarly constructed EA indices and bias cross-race comparisons.

Childhood Adversities as Determinants of Cardiovascular Disease Risk and Perceived Illness Burden in Adulthood: Comparing Retrospective and Prospective Self-Report Measures in a Longitudinal Sample of African Americans.

A large body of evidence suggests that exposure to childhood adversities increases risk for poor quality physical health in adulthood. Much of this evidence is based on retrospective measures which are believed to be contaminated by the limitations and biases of autobiographical memory. Using longitudinal data on 454 African Americans (61 percent female) this study examines the corroboration between prospective and retrospective measures of childhood adversities gathered approximately two decades apart, and the relative ability of the measures to predict self-reported illnesses and a biomarker of 30-year cardiovascular disease risk. Comparisons indicated that the retrospective and prospective measures demonstrated weak convergence and did not provide completely equivalent information about self-reported adverse childhood experiences. A series of regression models indicated that the two measures of adversities exhibited similar associations with the cardiovascular disease biomarker but divergent associations with self-reported illnesses. Furthermore, both the prospective and retrospective measures simultaneously predicted cardiovascular disease risk in adulthood. That the prospective measure did not significantly predict perceived illnesses after adjusting for the retrospective measure is evidence that childhood adversities predict self-reported health burden insofar as respondents remember those adversities as adults. The findings provide evidence that retrospective self-report measures of childhood adversities do not closely converge with prospective measures, and that retrospective measures may not provide valid estimates of the association between childhood adversities and perceived illnesses in adulthood.

Testing Life Course Models Whereby Juvenile and Adult Adversity Combine to Influence Speed of Biological Aging.

The present study extends prior research on the links between social adversity and aging by employing more comprehensive measures of adversity and a new gene expression index of aging. Hierarchical regression and 20 years of data from a sample of 381 black Americans were used to test models regarding the impact of social adversity on speed of aging. Consistent with the early life sensitivity model, early adversity continued to predict accelerated aging after controlling for adult adversity. Contrary to the pathway model, adult adversity was not related to aging following controls for early adversity. The cumulative stress model received partial support as high adversity during adulthood amplified the effect of early adversity on aging. Finally, consonant with the social change model, low adversity during adulthood buffered the effect of early adversity on aging. These findings held after controlling for health behaviors such as smoking, diet, and exercise.

The effect of early discrimination on accelerated aging among African Americans.

OBJECTIVE: This study examined the role of depressive symptoms in mediating the relationship between early life experiences of racial discrimination and accelerated aging in adulthood for African Americans (i.e., prediction over a 19-year period, from ages 10 to 29) after adjusting for gender and health behaviors. METHOD: Longitudinal self-report data over 7 waves of data collection from the Family and Community Health Study were utilized. The sample included 368 African Americans with usable gene expression data to compute accelerated aging, as well as complete data on all self-report variables including racial discrimination (Schedule of Racist Events) and depression (Diagnostic Interview Schedule for Children-Version 4). Blood was collected by antecubital blood draws from participants at age 29. The proposed model was tested by path analysis. RESULTS: Findings revealed that high discrimination at ages 10-15 was associated with depression at ages 20-29 (ß = .19, p = .001), controlling for depression at ages 10-15, which, in turn, was related to accelerated cellular-level aging (ß = .11, p = .048) after controlling for gender, alcohol consumption, and cigarette use. The indirect effect of racial discrimination on aging through depression at ages 20-29 was significant (ß = .021, 95% confidence interval [.001, .057]), accounting for 32.3% of the total variance. CONCLUSION: These findings support research conceptualizations that early life stress due to racial discrimination lead to sustained negative affective states continuing into young adulthood that confer risk for accelerated aging and possibly premature disease and mortality in African Americans. These findings advance knowledge of potential underlying mechanisms that influence racial health disparities. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Perceived relationship support moderates the association of contextual stress with inflammation among African Americans.

We followed 402 African American young adults from ages 24 to 29, a period of emerging committed relationships, to examine the association of contextual stress (CS), for example, experiences of financial strain, victimization, and racial discrimination, with inflammation, and to test predictions that greater perceived relationship warmth and support (PRWS) at age 29 would moderate the association between earlier CS and inflammation, using a multiplex assessment of cytokines to construct an index of the ratio between predominantly proinflammatory cytokines versus predominantly anti-inflammatory cytokines. CS experienced at age 24 was associated with greater inflammation at age 29 in the full sample (b = .112, p = .004). PRWS at age 29 moderated the association of earlier CS with inflammation (b = -.114, p = .011), but there was no significant main effect of PRWS (b = -.053, p = .265). Finally, using an internal moderator approach, we compared the association of CS with inflammation among those not in a committed relationship to those in more or less supportive relationships, showing a significant and stronger association of CS with inflammation for those with low PRWS (-1 SD; b = .182, p < .001), a weaker and nonsignificant association of CS with inflammation among those with higher PRWS (+1 SD; b = -.002, p = .975), and an intermediate and nonsignificant association of CS with inflammation among those with no committed romantic relationship (b = .077, p = .227). Results were robust to number of cytokines included in the inflammation index. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Neighborhood Disadvantage and Biological Aging: Using Marginal Structural Models to Assess the Link Between Neighborhood Census Variables and Epigenetic Aging.

OBJECTIVES: Past research has reported an association between neighborhood disadvantage and healthy aging, but most of these studies utilize self-report measures of health or physical functioning and do not properly account for neighborhood selection effects, creating concerns regarding inflated associations. To overcome these limitations and provide a more stringent estimate of effects, the current study investigated the effect of neighborhood disadvantage on aging using newly developed epigenetic methods to assess rate of biological aging and marginal structural modeling (MSM) to account for potential confounds due to neighborhood selection. METHODS: We tested the hypothesis that neighborhood disadvantage accelerates aging using U.S. census data and five waves of interview data from a sample of 100 middle-aged African American women. Using a recently developed epigenetic index of aging, biological age was measured using weighted methylation values at 71 CpG sites. We calculated a measure of accelerated methylomic aging (in years) based upon the residual scores resulting from a regression of methylomic age on chronological age. RESULTS: Controlling for a variety of individual difference factors that could be confounded with neighborhood effects, including various health behaviors, neighborhood disadvantage was associated with accelerated biological aging. Using MSM to account for selection effects, a standard deviation increase in neighborhood disadvantage accelerated aging an average of 9 months. CONCLUSIONS: Our findings converge with prior work to provide strong evidence that neighborhood context is a significant determinant of healthy aging.

Discrimination, segregation, and chronic inflammation: Testing the weathering explanation for the poor health of Black Americans.

Several studies have reported a relation between race-related stressors and the poor health of Black Americans. Such findings raise questions regarding the mediating biological mechanisms that might account for this link. The present study investigated elevated systemic inflammation, a factor shown to be a strong predictor of chronic illness and mortality in all ethnic populations, as a possible factor. Using 7 waves of data from the Family and Community Health Study, collected over a 20-year period from over 400 Black Americans, we investigated the extent to which exposure to discrimination and segregation at various points in the life course predicted adult inflammation at age 28. Our analyses examined whether cumulative stress, stress generation, or predictive adaptive response (PAR) models best accounted for any associations that existed between these race-related stressors and adult inflammation. At every wave of data collection, assessments of discrimination and segregation were related to adult inflammation. However, multivariate analyses using structure equation modeling indicated that the PAR model best explained the effect of these race-related stressors on inflammation. Exposure to discrimination and segregation during the juvenile years predicted adult inflammation and amplified the inflammatory effect of adult exposure to these race-related stressors. These effects were considerably more robust than that of traditional health risk factors such as diet, exercise, smoking, and low SES. Implications of these findings are discussed, including the limitations of the widely accepted risk factor approach to increasing the health of Black Americans. (PsycINFO Database Record

An index of the ratio of inflammatory to antiviral cell types mediates the effects of social adversity and age on chronic illness.

BACKGROUND: It is assumed that both social stress and chronological age increase the risk of chronic illness, in part, through their effect on systemic inflammation. Unfortunately, observational studies usually employ single-marker measures of inflammation (e.g., Interleukin-6, C-reactive protein) that preclude strong tests for mediational effects. OBJECTIVE: The present study investigated the extent to which the effects of socioeconomic disadvantage and age on onset of chronic illness is mediated by dominance of the innate (inflammatory) over the acquired (antiviral) components of the immune system. METHODS: We assessed inflammation using the ratio of inflammatory to antiviral cell types (ITACT Ratio). This approach provided a stronger test of evolutionary arguments regarding the effect of social stress on chronic inflammation than is the case with cytokine measures, and afforded an opportunity to replicate findings obtained utilizing mRNA. We used structural equation modeling and longitudinal data from a sample of 100 middle-age African American women to perform our analyses. RESULTS: Dominance of inflammatory over antiviral cell activity was associated with each of the eight illnesses included in our chronic illness measure. Both socioeconomic disadvantage and age were also associated with inflammatory dominance. Pursuant to the central focus of the study, the effects of socioeconomic adversity and age on increased illness were mediated by our measure of inflammatory dominance. The indirect effect of these variables through inflammatory cell profile was significant, with neither socioeconomic disadvantage nor age showing a significant association with illness once the impact of inflammatory cell profile was taken into account. CONCLUSIONS: First, the analysis provides preliminary validation of a new measure of inflammation that is calculated based on the ratio of inflammatory to antiviral white blood cells. Second, our results support the hypothesis that socioeconomic disadvantage and chronological age increase risk for chronic illness in part through their effect on inflammatory processes.

Parenting, Socioeconomic Status Risk, and Later Young Adult Health: Exploration of Opposing Indirect Effects via DNA Methylation.

A sample of 398 African American youth, residing in rural counties with high poverty and unemployment, were followed from ages 11 to 19. Protective parenting was associated with better health, whereas elevated socioeconomic status (SES) risk was associated with poorer health at age 19. Genome-wide epigenetic variation assessed in young adulthood (age 19), was associated with both SES risk and protective parenting. Three categories of genes were identified whose methylation was associated with parenting, SES risk, and young adult health. Methylation was a significant mediator of the impact of parenting and SES risk on young adult health. Variation in mononuclear white blood cell types was also examined and controlled, showing that it did not account for observed effects of parenting and SES risk on health.

Economic hardship and biological weathering: The epigenetics of aging in a U.S. sample of black women.

BACKGROUND: Past research has linked low socio-economic status (SES) to inflammation, metabolic dysregulation, and various chronic and age-related diseases such as type 2 diabetes, coronary heart disease, stroke, and dementia. These studies suggest that the challenges and adversities associated with low SES may result in premature aging and increased risk of morbidity and mortality. OBJECTIVE: Building upon this research, the present study investigates various avenues whereby low income might accelerate biological aging. METHODS: Structural equation modeling and longitudinal data from a sample of 100 Black, middle-aged women residing in the United States was used to investigate the effect of income on a recently developed epigenetic measure of biological aging. This measure can be used as a "biological clock" to assess, at any point during adulthood, the extent to which an individual is experiencing accelerated or decelerated biological aging. RESULTS: Low income displayed a robust association with accelerated aging that was unaffected after controlling for other SES-related factors such as education, marital status, and childhood adversity. Further, our analyses indicated that the association between income and biological aging was not explained by health-related behaviors such as diet, exercise, smoking, alcohol consumption, or having health insurance. Rather, in large measure, it was financial pressure (difficulty paying bills, buying necessities, or meeting daily expenses) that accounted for the association between low income and accelerated aging. CONCLUSIONS: These findings support the view that chronic financial pressures associated with low income exert a weathering effect that results in premature aging.

Constructing Confidence Intervals for Effect Size Measures of an Indirect Effect.

Confidence intervals for an effect size can provide the information about the magnitude of an effect and its precision as well as the binary decision about the existence of an effect. In this study, the performances of five different methods for constructing confidence intervals for ratio effect size measures of an indirect effect were compared in terms of power, coverage rates, Type I error rates, and widths of confidence intervals. The five methods include the percentile bootstrap method, the bias-corrected and accelerated (BCa) bootstrap method, the delta method, the Fieller method, and the Monte Carlo method. The results were discussed with respect to the adequacy of the distributional assumptions and the nature of ratio quantity. The confidence intervals from the five methods showed similar results for samples of more than 500, whereas, for samples of less than 500, the confidence intervals were sufficiently narrow to convey the information about the population effect sizes only when the effect sizes of regression coefficients defining the indirect effect are large.