Physical performance in older age predicts independence, and social factors influence physical function, yet the biological mechanisms are not well understood. Mitochondrial function—a new “hallmark of aging”—may explain how social experiences impact health, as its dysfunction is linked to multiple age-related diseases and declining physical performance. However, no field studies have examined links between mitochondria, physical function, and social determinants in aging populations. This project leverages a new method to measure mitochondrial bioenergetics from frozen blood samples, enabling analysis with existing large cohort data from the Health and Retirement Study. Our aims are to assess the relationships between socioeconomic status, mitochondrial capacity, and physical performance, and to test if mitochondrial health connects socioeconomic status to functional outcomes. This research may reveal a biological pathway linking social and health factors in aging.
This project will enhance basic genomic data from the 2014 wave of the Child Development Supplement to the Panel Study of Income Dynamics in a number of important ways. It will create new genomic measures, make them available to the research community free of charge, and promote their use through comprehensive documentation and outreach efforts. This project will allow researchers to use these new genomic measures to answer crucial scientific questions about how genetic propensity and social environment intervene to shape health, behavior, and well-being.
This project seeks to gather genotype data from 12,000 participants in the Understanding America Study panel to develop polygenic scores. These scores will be utilized in social-science genetic studies to examine factors influencing the risk of Alzheimer’s disease and related dementias.
Researchers involved in the project will:
- Guide genetic data collection and oversee all aspects of specimen collection, data processing, polygenic score construction, and data release.
- Lead analyses and the scientific presentation of the study’s findings.
- Provide expertise in sample collection, measurement, score construction, and genetic data analysis.
- Develop and implement cognitive measures and interpret the study results.
- Advise on genotyping quality control, data imputation, and the construction and analysis of polygenic scores.
Biological samples will be processed and stored at the ISR Biospecimen Lab (ISR-BSL) at the University of Michigan Institute for Social Research. The ISR-BSL will handle 12,000 saliva samples, including producing Oragene kits, receiving and processing the saliva, conducting DNA extraction, quantification, and aliquoting, and storing specimens. Following these steps, samples will be plated and sent to the Genetic Resources Core Facility (GRCF) at Johns Hopkins University for further analysis. The ISR-BSL will provide comprehensive documentation of sample management throughout the study.
Little is known about the extent to which the biological embedding of promotive and protective factors pre-loads a capacity for resilience across the life course. If researchers better understood how promotive and protective factors operate biologically we could better determine what causes depression, which children are most at risk, and perhaps most critically, the optimal times to intervene to delay (or prevent) first onsets of depression. We will address these gaps by discovering epigenetically-linked processes and time periods when positive life experiences promote resilience to depression.
Landscapes of Population Health (“Landscapes”) is an interdisciplinary research collective that includes historians, sociologists, psychologists, epidemiologists, and statisticians who bring their expertise in historical and contemporary racial violence and control, environmental justice, epigenomics, and population health to study the link between structural racism and population health. We bring together critical theories from the humanities and innovative potential biological mechanisms from the bench and medical sciences to better understand the root causes of patterns in population health. Our work includes active data collection, work on existing data sets, and the development and implementation of measures. In addition to our focus on the science itself, we are committed to changing the demography of the scholars who drive our epistemology.
Landscapes Collaborators outside of ISR
This project supports the analysis of existing social and epigenetic data for three countries and the development of longitudinal epigenetic data for three countries: the United States, Ireland, and the United Kingdome (Northern Ireland, specifically). The project will answer basic questions about how life circumstances in both childhood and adulthood affect epigenetic change and how that change is associated with health after age 50. Researchers in the three countries have a set of integrated aims and analyses using data from three national studies of aging in the family of Health and Retirement Studies: the US Health and Retirement Study (HRS), the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA), and the Irish Longitudinal Study of Aging (TILDA).
We will examine the links between lifetime social, economic, psychological, environmental and behavioral circumstances, and epigenetic markers related to aging and health, and subsequent health. Epigenetic modification is one of the hallmarks of aging, i.e. an underlying physiological change that can speedup or delay aging-related health outcomes. Faster aging is characteristic of people in adverse social circumstances. Epigenetic change, particularly DNA methylation (DNAm), appears to be especially influenced by adverse social circumstances, both at early ages and at later ages.
This project is unique in evaluating how a variety of social circumstances. Low levels of education and income, minority group membership, adverse childhood experiences, adult traumas, risky health behaviors, psychological states, and chronic stress, are associated with epigenetic markers in three different countries. These factors have somewhat different historical, social, and behavioral characteristics and operate in different health policy regimes. These differences allow for both replication where effects are hypothesized to be similar and differentiation where they are hypothesized to differ (e.g., where risk characteristics are differentially patterned by SES).
The researchers are uniquely placed with their collaborative resources to explore how socioeconomic experiences across the life course alter epigenetic profiles to influence health outcomes such as frailty, disability, chronic disease, and premature mortality. The three data sets have been highly harmonized for information collection from the beginning of the studies and were designed to encourage comparative analysis. They have been harmonized in the survey information and the development of the epigenetic data in the three countries. Each country has strong independent research teams who bring unique expertise and resources and a history of collaboration to this collaborative proposal.
While risk factors for cognitive decline and Alzheimer ’s disease and related dementias (ADRD) have been widely studied, there is still much unknown about the biological pathways that lead to ADRD. This project seeks to improve our understanding of the pathophysiology of cognitive decline and ADRD by examining the role of peripheral immunosenescence in these processes. A major gap in existing research is a lack of longitudinal studies that can establish an etiologic link between peripheral immunosenescence and development of incident ADRD. In addition, there are few population-based studies examining these processes in U.S. representative samples. Population-based studies can evaluate whether clinical findings among ADRD patients are generalizable to the broader population as well as examine the role of social determinants in these processes. Despite consistently observed social inequalities in ADRD, including based on race/ethnicity, sex/gender, and socioeconomic status, we do not yet understand the pathways by which social disadvantage lead to ADRD, limiting population-wide ADRD prevention strategies. Our long-term goal is to elucidate the role of population immunity in predicting ADRD. Our objective for this research is to evaluate the relationship between peripheral immunosenescence and domain-specific cognitive function, decline, and ADRD diagnoses in a nationally representative sample of older US adults, and, to examine the extent to which immunosenescence explains social inequalities in cognitive function, decline, and ADRD. Our central hypothesis is that immunosenescence, characterized by an increased number of senescent immune cells (e.g., CD8+CD45RA-, CD4+CD45RA-) and elevated inflammatory cytokines (C-Reactive Protein (CRP), interleukin (IL)-6, TNF-alpha) will be associated with worse cognitive outcomes, and that immunosenescence will partially explain some of the social inequalities in cognitive outcomes. Our rationale is that immunosenescence may be an important early risk factor for ADRD, potentially representing a biological mechanism explaining population heterogeneity and inequalities in ADRD risk. To investigate these relationships, we will pursue three specific aims:
- Determine the association between peripheral immunosenescence and cognitive function and decline in the Health and Retirement Study (HRS);
- Determine the association between peripheral immunosenescence and incident ADRD measured both by HRS cognitive assessment and linked Medicare claim data; and
- Determine the extent to which immunosenescence explains social inequalities in cognitive function, decline, and ADRD.
This project is the first large-scale population-based study of immunity and cognition. It will yield critical insights to our understanding of the pathophysiology of cognitive decline and ADRD, and inequalities in these processes. This project is significant because the results could point to new diagnostic tools able to discern profiles of immunosenescence predictive of ADRD in the peripheral blood.
The intergenerational persistence of poor health and poverty and the quest to understand underlying processes underscore the importance of rich multigenerational data. Very few existing datasets contain comprehensive information on social, environmental, and biological factors over the life course and across generations; lack of such data has seriously limited attempts to identify the processes shaping health disparities, economic inequalities, and causal linkages between the two. The Fragile Families and Child Wellbeing Study (FF) is the longest running birth-cohort study in the U.S The study is based on a national probability sample and follows parents — both mothers and fathers — and their children who were born in 1998-2000. Based on birth statistics, the children in FF are now having children of their own. We are expanding the FF study by conducting a perinatal survey on the health of this third generation of children, early parenthood experiences of the second generation. We are examining the characteristics of households and families into which the third generation are born, as well as collecting biological specimens from the new children and their non-FF parents. The augmented data will have many unique and valuable features, including:
- extensive data on three generations of families: children, parents, and grandparents;
- data on siblings and half-siblings (in the third generation);
- three generations of exposures and genetic and epigenetic data;
- genetic data on trios (third generation children and both of their parents); and
- comprehensive data on perinatal health (pre-pregnancy, prenatal, delivery, neonatal, and postpartum factors including breastfeeding and postpartum depression) and circumstances in the second and third generations.
The Fragile Families Third Generation study will facilitate novel and important analyses of intergenerational transmission of health, intergenerational relationships within families, and gene-environment effects on health. It will also provide an essential foundation for future third generation data collection at subsequent developmental transitions including school readiness and emerging adulthood.
Cardiometabolic disease and management of its risk factors, such as hypertension, dyslipidemia, adiposity and type II diabetes, constitute a major public health burden across diverse populations. Therefore, understanding the genetic and environmental (lifestyle) factors and their interactions may provide insights into intervention, prevention and therapeutic strategies for addressing this burden. Several genome-wide association studies (GWAS) led by consortia such as CHARGE, ICBP and GIANT, have revolutionized genetic discoveries for many complex traits by using “genetic main effects” approaches. But despite increased attention to diversity in human genomics research, the number of GWAS and genome-wide interaction studies (GWIS) in non-European populations are limited. In contrast, the interplay between lifestyle/environment and genetics with an emphasis on diverse populations is a key part of the Precision Medicine Initiative (PMI) and the PMI Cohort targeting 1 million or more participants.
The objective of this study is to identify novel genetic loci associated with cardiometabolic traits, to investigate gene-lifestyle interactions through a focused study of the cardiometabolic trait loci, and to characterize the molecular effects underlying the interactions by leveraging existing ‘omics’ data such as DNA methylation, gene expression, and metabolites. By investigating genomic and environmental contributors to health outcomes across diverse populations, this project reflects the priorities of the PMI.
This project will evaluate gene-lifestyle interactions across diverse populations (European, African, Hispanic, and Asian). Building on our current progress, we will expand the current focus on blood pressure and lipids to include other cardiometabolic (adiposity and diabetes) traits; expand the currently dichotomized lifestyle factors (smoking, alcohol, physical activity, education, psychosocial, and sleep duration), by adding sleep duration, quantitative lifestyle exposures (e.g., cigarettes per day), and an Aggregate Lifestyle Index as an overall lifestyle risk factor for cardiometabolic health; and vastly increase the sample size to achieve greater statistical power.
We will add substantially large existing studies to those currently participating in our projects. These studies include the Million Veteran Program (N~234,000), the UK Biobank (N~478,000), the Biobank Japan (N~160,000), the Study of Latinos (N~13,000), among others. The overall sample size is 1.267 million, consisting of 912,000 European, 91,000 African, 33,000 Hispanic, and 231,000 Asian individuals. This represents the most significant effort to date to investigate interactions with an aggregate sample size of about 1.267 million. The extension of this project may lead to new diagnostic and therapeutic tools, contribute to precision care in the management of cardiometabolic disorders, and provide insights for the PMI, thus potentially impacting clinical practice.
The overall purpose of this research program is to understand how stress and social contexts affect health and the biopsychosocial factors that account for those links. We seek to foster a multidisciplinary collaboration that capitalizes on advances in mobile technology and biopsychosocial methods to gain better understanding of social, psychological and biological factors influencing healthy aging.