Association between factors in life course and physiological disorders among the middle-aged and older population in Zhoushan city of Zhejiang province. / æµ™æ±ŸçœèˆŸå±±å¸‚ä¸­è€å¹´äººç¾¤ç”Ÿå‘½åŽ†ç¨‹å› ç´ ä¸Žç”Ÿç†å¤±è°ƒçš„å ³è”ç ”ç©¶.

OBJECTIVES: To analyze the associations between factors in life course and physiological disorders in the middle-aged and elderly population of Zhoushan city of Zhejiang province, and the mediating roles of lifestyle and mental health. METHODS: A total of 1553 island residents aged ≥45 years were enrolled from the Zhejiang Metabolic Syndrome Cohort Zhoushan Liuheng Sub-cohort. The demographic information, life-course information, lifestyle, and mental health information of participants were documented, and blood samples of were collected. The status of aging was evaluated by physiological disorders calculation model developed by authors previously. The Shapley value decomposition method was used to assess the cumulative and relative contribution of multiple factors in life course to the aging. Principal component analysis and hierarchical cluster analysis were used to classify subgroups. General linear regression model was used to assess the associations between the life-course subgroups and physiological disorders. Five key factors associated with aging were finally identified. Logistic regression model, general linear regression model, and mediation analysis model were used to assess the complex associations between life-course subgroups, key factors, unhealthy lifestyle, mental health, and aging. RESULTS: Shapley value decomposition method indicated that eight types of life-course factors explained 6.63% (SE=0.0008) of the individual physiological disorders variance, with the greatest relative contribution (2.78%) from adversity experiences in adulthood. The study participants were clustered into 4 subgroups, and subgroups experiencing more adversity in adulthood and having low educational attainment or experiencing more trauma and having poorer relationships in childhood had significantly higher levels of physiological disorders. Life-course subgroups and key factors (childhood trauma and health, adversity experience in adulthood, and lower education) were positively associated with unhealthy lifestyles (ß=0.12-0.41, P<0.05). In addition, life-course subgroups and key factors (adversity experience in adulthood) were positively associated with psychological problems (OR=2.14-4.68, P<0.05). Unhealthy lifestyle scores showed a marginal significant association with physiological disorders (ß=0.03, P=0.055). However, no significant association was found between psychological problems and physiological disorders (ß=0.03, P=0.748). The results of the mediation analysis model suggested that unhealthy lifestyles partially mediated the associations between life-course subgroups, adversity experience in adulthood and physiological disorders. CONCLUSIONS: Multiple life-course factors contribute about 6% of the variance in physiological disorders in the middle aged and elderly population of the study area; subgroups with adverse life course experiences have higher levels of aging; and the association may be partially mediated by unhealthy lifestyles.

An objective metric of individual health and aging for population surveys.

BACKGROUND: We have previously developed and validated a biomarker-based metric of overall health status using Mahalanobis distance (DM) to measure how far from the norm of a reference population (RP) an individual's biomarker profile is. DM is not particularly sensitive to the choice of biomarkers; however, this makes comparison across studies difficult. Here we aimed to identify and validate a standard, optimized version of DM that would be highly stable across populations, while using fewer and more commonly measured biomarkers. METHODS: Using three datasets (the Baltimore Longitudinal Study of Aging, Invecchiare in Chianti and the National Health and Nutrition Examination Survey), we selected the most stable sets of biomarkers in all three populations, notably when interchanging RPs across populations. We performed regression models, using a fourth dataset (the Women's Health and Aging Study), to compare the new DM sets to other well-known metrics [allostatic load (AL) and self-assessed health (SAH)] in their association with diverse health outcomes: mortality, frailty, cardiovascular disease (CVD), diabetes, and comorbidity number. RESULTS: A nine- (DM9) and a seventeen-biomarker set (DM17) were identified as highly stable regardless of the chosen RP (e.g.: mean correlation among versions generated by interchanging RPs across dataset of r = 0.94 for both DM9 and DM17). In general, DM17 and DM9 were both competitive compared with AL and SAH in predicting aging correlates, with some exceptions for DM9. For example, DM9, DM17, AL, and SAH all predicted mortality to a similar extent (ranges of hazard ratios of 1.15-1.30, 1.21-1.36, 1.17-1.38, and 1.17-1.49, respectively). On the other hand, DM9 predicted CVD less well than DM17 (ranges of odds ratios of 0.97-1.08, 1.07-1.85, respectively). CONCLUSIONS: The metrics we propose here are easy to measure with data that are already available in a wide array of panel, cohort, and clinical studies. The standardized versions here lose a small amount of predictive power compared to more complete versions, but are nonetheless competitive with existing metrics of overall health. DM17 performs slightly better than DM9 and should be preferred in most cases, but DM9 may still be used when a more limited number of biomarkers is available.

Obesogenic environments and cardiovascular disease: a path analysis using US nationally representative data.

INTRODUCTION: People living in obesogenic environments, with limited access to healthful food outlets and exercise facilities, generally have poor health. Previous research suggests that behavioral risk factors and indicators of physiological functioning may mediate this link; however, no studies to date have had the requisite data to investigate multi-level behavioral and physiological risk factors simultaneously. The present study conducted serial and parallel mediation analyses to examine behavioral and physiological pathways explaining the association between environmental obesogenicity and cardiovascular disease (CVD). METHODS: This cross-sectional observational study used data from the 2012-2016 Health and Retirement Study, a representative survey of US older adults (n = 12,482, mean age 65.9). Environmental obesogenicity was operationalized as a combined score consisting of nine environmental measures of food and physical activity. CVD and health-compromising behaviors (diet, alcohol consumption, smoking, and exercise) were self-reported. Physiological dysregulation was assessed with measured blood pressure, heart rate, HbA1c, cholesterol levels, BMI, and C-reactive protein. The Hayes Process Macro was used to examine serial and parallel paths through health-compromising behaviors and physiological dysregulation in the environmental obesogenicity-CVD link. RESULTS: People living in more obesogenic environments had greater odds of self-reported CVD (odds ratio = 1.074, 95% confidence interval (CI): 1.028, 1.122), engaged in more health-compromising behaviors (ß = 0.026, 95% CI: 0.008, 0.044), and had greater physiological dysregulation (ß = 0.035, 95% CI: 0.017, 0.054). Combined, health-compromising behaviors and physiological dysregulation accounted for 7% of the total effects of environmental obesogenicity on CVD. CONCLUSION: Behavioral and physiological pathways partially explain the environmental obesogenicity-CVD association. Obesogenic environments may stymie the success of cardiovascular health-promotion programs by reducing access to resources supporting healthy lifestyles.

Coenzyme A Restriction as a Factor Underlying Pre-Eclampsia with Polycystic Ovary Syndrome as a Risk Factor.

Pre-eclampsia is the most common pregnancy complication affecting 1 in 20 pregnancies, characterized by high blood pressure and signs of organ damage, most often to the liver and kidneys. Metabolic network analysis of published lipidomic data points to a shortage of Coenzyme A (CoA). Gene expression profile data reveal alterations to many areas of metabolism and, crucially, to conflicting cellular regulatory mechanisms arising from the overproduction of signalling lipids driven by CoA limitation. Adverse feedback loops appear, forming sphingosine-1-phosphate (a cause of hypertension, hypoxia and inflammation), cytotoxic isoketovaleric acid (inducing acidosis and organ damage) and a thrombogenic lysophosphatidyl serine. These also induce mitochondrial and oxidative stress, leading to untimely apoptosis, which is possibly the cause of CoA restriction. This work provides a molecular basis for the signs of pre-eclampsia, why polycystic ovary syndrome is a risk factor and what might be done to treat and reduce the risk of disease.

Evidence from two cohorts for the frailty syndrome as an emergent state of parallel dysregulation in multiple physiological systems.

Frailty is a clinical syndrome often present in older adults and characterized by a heightened vulnerability to stressors. The biological antecedents and etiology of frailty are unclear despite decades of research: frailty is associated with dysregulation in a wide range of physiological systems, but no specific cause has been identified. Here, we test predictions stemming from the hypothesis that there is no specific cause: that frailty is an emergent property arising from the complex systems dynamics of the broad loss of organismal homeostasis. Specifically, we use dysregulation of six physiological systems using the Mahalanobis distance approach in two cohorts of older adults to test the breadth, diffuseness, and nonlinearity of associations between frailty and system-specific dysregulation. We find clear support for the breadth of associations between frailty and physiological dysregulation: positive associations of all systems with frailty in at least some analyses. We find partial support for diffuseness: the number of systems or total amount of dysregulation is more important than the identity of the systems dysregulated, but results only partially replicate across cohorts. We find partial support for nonlinearity: trends are exponential but not always significantly so, and power is limited for groups with very high levels of dysregulation. Overall, results are consistent with-but not definitive proof of-frailty as an emergent property of complex systems dynamics. Substantial work remains to understand how frailty relates to underlying physiological dynamics across systems.

When Is Hope Enough? Hopefulness, Discrimination and Racial/Ethnic Disparities in Allostatic Load.

Hopefulness is associated with better health and may be integral for stress adaptation and resilience. Limited research has prospectively examined whether hopefulness protects against physiological dysregulation or does so similarly for U.S. whites, blacks and Hispanics. We examined the association between baseline hopefulness and future allostatic load using data from the Health and Retirement Study (n = 8,486) and assessed differences in this association by race/ethnicity and experiences of discrimination. Four items measured hopefulness and allostatic load was a count of seven biomarkers for which a respondent's measured value was considered high-risk for disease. A dichotomous variable assessed whether respondents experienced at least one major act of discrimination in their lifetime. We used Poisson regression to examine the association between hopefulness and allostatic load and included a multiplicative interaction term to test racial/ethnic differences in this association. Subsequent analyses were stratified by race/ethnicity and tested the interaction between hopefulness and discrimination within each racial/ethnic group. Hopefulness was associated with lower allostatic load scores, but its effects varied significantly by race/ethnicity. Race-stratified analyses suggested that hopefulness was protective among whites and not associated with allostatic load among Hispanics irrespective of experiencing discrimination. Hopefulness was associated with lower allostatic load among blacks reporting discrimination but associated with higher allostatic load among those who did not. Findings suggest that hopefulness plays differing roles for older whites, blacks and Hispanics and, for blacks, its protective effects on physiological dysregulation are intricately tied to their experiences of discrimination.

Social relationships and physiological determinants of longevity across the human life span.

Two decades of research indicate causal associations between social relationships and mortality, but important questions remain as to how social relationships affect health, when effects emerge, and how long they last. Drawing on data from four nationally representative longitudinal samples of the US population, we implemented an innovative life course design to assess the prospective association of both structural and functional dimensions of social relationships (social integration, social support, and social strain) with objectively measured biomarkers of physical health (C-reactive protein, systolic and diastolic blood pressure, waist circumference, and body mass index) within each life stage, including adolescence and young, middle, and late adulthood, and compare such associations across life stages. We found that a higher degree of social integration was associated with lower risk of physiological dysregulation in a dose-response manner in both early and later life. Conversely, lack of social connections was associated with vastly elevated risk in specific life stages. For example, social isolation increased the risk of inflammation by the same magnitude as physical inactivity in adolescence, and the effect of social isolation on hypertension exceeded that of clinical risk factors such as diabetes in old age. Analyses of multiple dimensions of social relationships within multiple samples across the life course produced consistent and robust associations with health. Physiological impacts of structural and functional dimensions of social relationships emerge uniquely in adolescence and midlife and persist into old age.

Prenatal stress enhances postnatal plasticity: The role of microbiota.

Separate fields of inquiry indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity and (b) that these postnatal phenotypes are themselves associated with increased susceptibility to both positive and negative environmental influences. Collectively, this work supports Pluess and Belsky's (Psychopathology, 2011, 23, 29) claim that prenatal stress fosters, promotes or "programs" postnatal developmental plasticity. Herein, we review animal and human evidence consistent with this hypothesis before advancing the novel idea that infant intestinal microbiota may be one candidate mechanism for instantiating developmental plasticity as a result of prenatal stress. We then review research indicating that prenatal stress predicts differences in infant intestinal microbiota; that infant intestinal microbiota is associated with behavioral and physiological reactivity phenotypes; and, thus, that prenatal stress may influence infant intestinal microbiota in a way that results in heightened physiological and behavioral reactivity and, thereby, postnatal developmental plasticity. Finally, we offer ideas for testing this claim and consider implications for intervention and use of probiotics during early infancy.

The first multi-zoo application of an allostatic load index to western lowland gorillas (Gorilla gorilla gorilla).

Vertebrate stress responses are highly adaptive biological functions, maximizing survival probability in life-threatening situations. However, experiencing repeated and/or chronic stressors can generate physiological dysregulation and lead to disease. Because stress responses are multi-systemic and involve a wide range of physiological functions, identifying responses to stressors is best accomplished using integrated biomarker models. Allostatic load, defined as the physiological dysregulation that accumulates over the lifespan due to stressful experiences, is one such model. Allostatic load is measured using allostatic load indices, which are composites of biomarkers from multiple somatic systems. Previously, we reported the use of a 7-biomarker allostatic load index (albumin, CRH, cortisol, DHEA-S, glucose, IL-6, TNF-α) in western lowland gorillas housed at a single zoo. Herein, this index is expanded to examine allostatic load responses to lifetime stressors in gorillas from two additional zoos (n = 63) as well as two pooled samples. The index was created using quartile cut-points for each biomarker. Significant associations were observed between multiple predictor variables and allostatic load, including sex, age, number of stressful events (anesthetic events, zoo transfers, agonistic interactions with wounding, pregnancies), and rearing history (mother-reared, nursery-reared, wild-caught). Additionally, allostatic load was associated with indicators of morbidity (creatinine, cholesterol, triglycerides), age at death, and mortality risk. These results are consistent with those reported in human allostatic load research, suggesting allostatic load indices have potential as an investigative and clinical tool for gorillas and other great apes.

Assessment of cumulative health risk in the World Trade Center general responder cohort.

BACKGROUND: Multiple comorbidities have been reported among rescue/recovery workers responding to the 9/11/2001 WTC disaster. In this study, we developed an index that quantifies the cumulative physiological burden of comorbidities and predicts life expectancy in this cohort. METHODS: A machine learning approach (gradient boosting) was used to model the relationship between mortality and several clinical parameters (laboratory test results, blood pressure, pulmonary function measures). This model was used to construct a risk index, which was validated by assessing its association with a number of health outcomes within the WTC general responder cohort. RESULTS: The risk index showed significant associations with mortality, self-assessed physical health, and onset of multiple chronic conditions, particularly COPD, hypertension, asthma, and sleep apnea. CONCLUSION: As an aggregate of several clinical parameters, this index serves as a cumulative measure of physiological dysregulation and could be utilized as a prognostic indicator of life expectancy and morbidity risk.

Complex systems dynamics in aging: new evidence, continuing questions.

There have long been suggestions that aging is tightly linked to the complex dynamics of the physiological systems that maintain homeostasis, and in particular to dysregulation of regulatory networks of molecules. This review synthesizes recent work that is starting to provide evidence for the importance of such complex systems dynamics in aging. There is now clear evidence that physiological dysregulation--the gradual breakdown in the capacity of complex regulatory networks to maintain homeostasis--is an emergent property of these regulatory networks, and that it plays an important role in aging. It can be measured simply using small numbers of biomarkers. Additionally, there are indications of the importance during aging of emergent physiological processes, functional processes that cannot be easily understood through clear metabolic pathways, but can nonetheless be precisely quantified and studied. The overall role of such complex systems dynamics in aging remains an important open question, and to understand it future studies will need to distinguish and integrate related aspects of aging research, including multi-factorial theories of aging, systems biology, bioinformatics, network approaches, robustness, and loss of complexity.

Emotional and instrumental support during childhood and biological dysregulation in midlife.

OBJECTIVE: To determine whether greater emotional and instrumental support during childhood is associated with less dysregulation across multiple physiological systems in midlife. METHODS: Data are from participants in the second wave of the Midlife in the United States study (2004-2005) who participated in a clinic-based assessment of health status. Emotional and instrumental support was measured using a seven-item scale (α=0.89) based on participant retrospective self-report. Biological dysregulation was assessed using an allostatic load (AL) score constructed from 24 measures across seven physiological systems (N=1236, aged 34-84 years). RESULTS: Emotional and instrumental support in childhood was associated with lower AL in a monotonic fashion: compared to individuals in the lowest quartile of support, respondents in the second, third, and fourth quartiles had -0.08 (standard deviation (SD)=0.08), -0.13 (SD=0.08) and -0.21 (SD=0.08) units lower AL, adjusting for age, sex, and race. This pattern was maintained after adjustment for reporting bias, childhood socioeconomic disadvantage, past-year depression, and physician-diagnosed cardiovascular disease or diabetes (p≤0.01). The inflammation and metabolic-lipid subscales showed the strongest associations. CONCLUSIONS: Greater emotional and instrumental support in childhood was associated with less biological dysregulation in midlife, even after accounting for socioeconomic disadvantage in childhood and other potential confounders.

Health for Hearts United Longitudinal Trial: Improving Perceived Stress and Allostatic Load Outcomes of Mid-Life and Older African American Women.

Cardiovascular disease (CVD) continues to be the leading cause of death in the United States, with African Americans experiencing higher age-adjusted mortality compared to Whites. African American women in particular carry a high CVD burden due to more exposure to adverse personal and socioenvironmental challenges. Church-based interventions can improve health behaviors and health status of African Americans, yet few have addressed stress-related health. The purpose of this study was to determine the effectiveness of the 18-month Health for Hearts United intervention in relation to stress-related outcomes (perceived stress, allostatic load) of mid-life and older African American women (≥45 years of age; n = 152 overall sample, n = 65 clinical subsample). The results of the repeated measures analysis of variance (ANOVA) analyses showed overall significant decreases in perceived stress and allostatic load for both treatment and comparison groups over the measurement occasions (baseline and 18 months) with educational level remaining as a significant correlate over time. There was no significant interaction between treatment and time, yet there were trends in improvements for the treatment group compared to the comparison group. The findings demonstrate the potential of church-based interventions in reducing both self-reported stress and allostatic load in African American women, and highlight the need for further investigation of educational level and other possible factors influencing stress management in these settings.

Interactions between genes involved in physiological dysregulation and axon guidance: role in Alzheimer's disease.

Dysregulation of physiological processes may contribute to Alzheimer's disease (AD) development. We previously found that an increase in the level of physiological dysregulation (PD) in the aging body is associated with declining resilience and robustness to major diseases. Also, our genome-wide association study found that genes associated with the age-related increase in PD frequently represented pathways implicated in axon guidance and synaptic function, which in turn were linked to AD and related traits (e.g., amyloid, tau, neurodegeneration) in the literature. Here, we tested the hypothesis that genes involved in PD and axon guidance/synapse function may jointly influence onset of AD. We assessed the impact of interactions between SNPs in such genes on AD onset in the Long Life Family Study and sought to replicate the findings in the Health and Retirement Study. We found significant interactions between SNPs in the UNC5C and CNTN6, and PLXNA4 and EPHB2 genes that influenced AD onset in both datasets. Associations with individual SNPs were not statistically significant. Our findings, thus, support a major role of genetic interactions in the heterogeneity of AD and suggest the joint contribution of genes involved in PD and axon guidance/synapse function (essential for the maintenance of complex neural networks) to AD development.

Towards a consensus definition of allostatic load: a multi-cohort, multi-system, multi-biomarker individual participant data (IPD) meta-analysis.

BACKGROUND: Allostatic load (AL) is a multi-system composite index for quantifying physiological dysregulation caused by life course stressors. For over 30 years, an extensive body of research has drawn on the AL framework but has been hampered by the lack of a consistent definition. METHODS: This study analyses data for 67,126 individuals aged 40-111 years participating in 13 different cohort studies and 40 biomarkers across 12 physiological systems: hypothalamic-pituitary-adrenal (HPA) axis, sympathetic-adrenal-medullary (SAM) axis, parasympathetic nervous system functioning, oxidative stress, immunological/inflammatory, cardiovascular, respiratory, lipidemia, anthropometric, glucose metabolism, kidney, and liver. We use individual-participant-data meta-analysis and exploit natural heterogeneity in the number and type of biomarkers that have been used across studies, but a common set of health outcomes (grip strength, walking speed, and self-rated health), to determine the optimal configuration of parameters to define the concept. RESULTS: There was at least one biomarker within 9/12 physiological systems that was reliably and consistently associated in the hypothesised direction with the three health outcomes in the meta-analysis of these cohorts: dehydroepiandrosterone sulfate (DHEAS), low frequency-heart rate variability (LF-HRV), C-reactive protein (CRP), resting heart rate (RHR), peak expiratory flow (PEF), high density lipoprotein cholesterol (HDL-C), waist-to-height ratio (WtHR), HbA1c, and cystatin C. An index based on five biomarkers (CRP, RHR, HDL-C, WtHR and HbA1c) available in every study was found to predict an independent outcome - mortality - as well or better than more elaborate sets of biomarkers. DISCUSSION: This study has identified a brief 5-item measure of AL that arguably represents a universal and efficient set of biomarkers for capturing physiological 'wear and tear' and a further biomarker (PEF) that could usefully be included in future data collection.

Adverse childhood experiences and low socioeconomic status with respect to allostatic load in adulthood: A systematic review.

Early-life psychosocial stress primes a number of health risk behaviors, and contributes to the development of various mental and somatic disorders in adulthood. It has been reported that adverse childhood experiences (ACEs) and low socioeconomic status (SES) might be associated with allostatic load (AL) in adulthood. In turn, elevated AL index has been found to predict a number of unfavorable health outcomes. Therefore, we aimed to perform a systematic review of studies investigating the association of ACEs and childhood SES with AL in adult populations. Independent online searches covered the publication period up to 20th Jun 2021. A total of 27 studies were included in qualitative synthesis. The majority of eligible studies showed that ACEs (14 out of 19 studies recording ACEs, 73.7%) and low childhood SES (11 out of 12 studies recording childhood SES, 91.7%) are associated with elevated AL in adults. However, several processes were found to mediate or moderate this association. These include educational attainments, social support, health behaviors, adult stress, post-traumatic stress disorder, coping strategies and aging. Moreover, a substantial methodological heterogeneity of approaches to calculating the AL index was observed. Apart from reports from overlapping samples, none of eligible studies used the same set of biomarkers. Findings from this systematic review imply that early-life psychosocial stress might have a lasting impact on biological dysregulations captured by the AL index. Future studies need to explore whether the association between early-life stress and the AL index accounts for the development of specific health outcomes.

Diet Quality and Biological Risk in a National Sample of Older Americans.

Objectives: Using comprehensive measures of biological risk, this study aims to investigate the relationship between intake of individual dietary components, overall diet quality, and biological dysregulation. Methods: We analyzed nationally representative data from 3734 older adults who participated in the Health and Retirement Study Venous Blood Study in 2016 and Health Care and Nutrition Survey in 2013. Results: Eleven out of 13 individual dietary components were associated with lower biological risk. Respondents with poor/suboptimal quality diet had higher biological risk than those with good quality diet. Discussion: Findings from this study emphasize the importance of healthy eating in improving health of older adults. Encouraging intake of fruits, greens and beans, whole grains, and fatty acids, while limiting consumption of sodium, added sugar, and saturated fat would improve overall diet quality and contribute to the prevention of chronic diseases and morbidity.

Contribution of life course circumstances to the acceleration of phenotypic and functional aging: A retrospective study.

Background: Accelerated aging leads to increasing burdens of chronic diseases in late life, posing a huge challenge to the society. With two well-developed aging measures (i.e., physiological dysregulation [PD] and frailty index [FI]), this study aimed to evaluate the relative contributions of life course circumstances (e.g., childhood and adulthood socioeconomic status) to variance in aging. Methods: We assembled data for 6224 middle-aged and older adults in China from the 2014 life course survey (June to December 2014), the 2015 biomarker collection (July 2015 to January 2016), and the 2015 main survey (July 2015 to January 2016) of the China Health and Retirement Longitudinal Study. Two aging measures (PD and FI) were calculated, with a higher value indicating more accelerated aging. Life course circumstances included childhood (i.e., socioeconomic status, war, health, trauma, relationship, and parents' health) and adulthood circumstances (i.e., socioeconomic status, adversity, and social support), demographics, and behaviours. The Shapley value decomposition, hierarchical clustering, and general linear regression models were performed. Findings: The Shapley value decomposition revealed that all included life course circumstances accounted for about 6·3% and 29·7% of variance in PD and FI, respectively. We identified six subpopulations who shared similar patterns in terms of childhood and adulthood circumstances. The most disadvantaged subpopulation (i.e., subpopulation 6 [more childhood trauma and adulthood adversity]) consistently exhibited accelerated aging indicated by the two aging measures. Relative to the most advantaged subpopulation (i.e., subpopulation 1 [less childhood trauma and adulthood adversity]), PD and FI in the most disadvantaged subpopulation were increased by an average of 0·14 (i.e., coefficient, by one-standard deviation, 95% confidence interval [CI] 0·06-0·21; p < 0·0001) and 0·10 (by one-point, 95% CI 0·09-0·11; p < 0·0001), respectively. Interpretation: Our findings highlight the different contributions of life course circumstances to phenotypic and functional aging. Special attention should be given to promoting health for the disadvantaged subpopulation and narrowing their health gap with advantaged counterparts. Funding: National Natural Science Foundation of China, Milstein Medical Asian American Partnership Foundation, Natural Science Foundation of Zhejiang Province, Fundamental Research Funds for the Central Universities, National Institute on Aging, National Centre for Advancing Translational Sciences, and Yale Alzheimer's Disease Research Centre.

The mediating role of allostatic load in the relationship between early life adversity and cognitive function across the adult lifespan.

Early life adversity is consequential for poor cognitive health in mid to late-life. Early life adversity is associated with higher allostatic load, a biological indicator of physiological dysregulation due to cumulative wear-and-tear from chronic stress. Higher allostatic load is also associated with poorer cognitive function across the lifespan. To date, a paucity of research has examined allostatic load as a mechanism through which early life adversity impacts cognition in adulthood. Using cross-sectional data from the Midlife in the United States (MIDUS) Study, the objective of the current study was to investigate the mediating role of allostatic load in the relationship between early life adversity and cognitive performance (global cognition, episodic memory, executive function) among middle-aged and older adults without cognitive impairment (n = 1541, Mage=53 ± 12, 53% female). Early life adversity was measured retrospectively using the Childhood Trauma Questionnaire. Allostatic load was composed of 20 biomarker proxies of neuroendocrine, metabolic, inflammatory, and cardiovascular systems, stratified by sex. Cognitive performance was evaluated using a battery of standardized neuropsychological tests. Controlling for age, education, and race, allostatic load significantly mediated the relationship between early life adversity and global cognition (ß=-0.01, 95%CI [-0.01,-0.001]), and early life adversity and executive function (ß=-0.01, 95%CI [-0.01,-0.001]), but not episodic memory. Findings did not change after controlling for lifestyle behaviours and current depression. Consistent with the biopsychosocial lifespan model of cognitive aging, findings suggest that early life adversity may become biologically embedded over time to negatively impact cognitive function in later adulthood in a domain-specific manner.

Rising childhood income inequality and declining Americans' health.

Morbidity and mortality are on the rise among Baby Boomers and younger cohorts. This study investigates whether this unfavorable health trend across birth cohorts 1925-1999 is related to rising income inequality Americans face during childhood. We use two nationally representative datasets: National Health and Nutrition Examination Surveys (NHANES) 1988-2018 and Panel Studies of Income Dynamics (PSID) 1968-2013, and two health outcomes: biomarkers of physiological dysregulation, and a chronic disease index. Childhood income inequality is measured by the average of the Gini index at the national level each birth cohort is exposed to between birth and age 18, where the Gini index from 1925 to 2016 is computed based on Internal Revenue Service income data. By merging childhood income inequality to individual level data from NHANES or PSID based on birth cohort, we find childhood income inequality is positively associated with the risk of physiological dysregulation in adulthood for all gender and racial groups in the NHANES data. It is also significantly related to the risk of chronic disease in the PSID data. This association is robust to controls for individual level childhood health and family background, adulthood socioeconomic and marital status, and contemporary macro socioeconomic factors. More importantly, childhood income inequality exposure explains a substantial amount of variation in these two health outcomes across cohorts, a pattern not observed for other early life exposures that display negative temporal trends similar to those for childhood income inequality. This study provides important evidence that income inequality experienced during childhood may have a long-lasting negative consequence for adult health, which partially explains the adverse health trends experienced by Baby Boomers and younger cohorts in the United States.