Genetic associations with longevity are on average stronger in females than in males.

It is long observed that females tend to live longer than males in nearly every country. However, the underlying mechanism remains elusive. In this study, we discovered that genetic associations with longevity are on average stronger in females than in males through bio-demographic analyses of genome-wide association studies (GWAS) dataset of 2178 centenarians and 2299 middle-age controls of Chinese Longitudinal Healthy Longevity Study (CLHLS). This discovery is replicated across North and South regions of China, and is further confirmed by North-South discovery/replication analyses of different and independent datasets of Chinese healthy aging candidate genes with CLHLS participants who are not in CLHLS GWAS, including 2972 centenarians and 1992 middle-age controls. Our polygenic risk score analyses of eight exclusive groups of sex-specific genes, analyses of sex-specific and not-sex-specific individual genes, and Genome-wide Complex Trait Analysis using all SNPs all reconfirm that genetic associations with longevity are on average stronger in females than in males. Our discovery/replication analyses are based on genetic datasets of in total 5150 centenarians and compatible middle-age controls, which comprises the worldwide largest sample of centenarians. The present study's findings may partially explain the well-known male-female health-survival paradox and suggest that genetic variants may be associated with different reactions between males and females to the same vaccine, drug treatment and/or nutritional intervention. Thus, our findings provide evidence to steer away from traditional view that "one-size-fits-all" for clinical interventions, and to consider sex differences for improving healthcare efficiency. We suggest future investigations focusing on effects of interactions between sex-specific genetic variants and environment on longevity as well as biological function.

Black/white differences in the relationship between debt and risk of heart attack across cohorts.

Background: Numerous studies show that increasing levels of education, income, assets, and occupational status are linked to greater improvements in White adults' health than Black adults'. Research has yet to determine, however, whether there are racial differences in the relationship between health and debt and whether this relationship varies across cohorts. Methods: Using data from the 1992-2018 Health and Retirement Study, we use survival analyses to examine the link between debt and heart attack risk among the Prewar Cohort, born 1931-1941, and Baby Boomers, born 1948-1959. Results: Higher unsecured debt is associated with increased heart attack risk for Black adults, especially among Baby Boomers and during economic recessions. Higher mortgage debt is associated with lower risk of heart attack for White but not Black Baby Boomers. The relationship between debt and heart attack risk remains after controlling for health behaviors, depressive symptoms, and other economic resources that are concentrated among respondents with high levels of debt. Conclusion: Debt is predictive of heart attack risk, but the direction and strength of the relationship varies by type of debt, debtors' racial identity, and economic context.

Landfall After the Perfect Storm: Cohort Differences in the Relationship Between Debt and Risk of Heart Attack.

Analyses of the Health and Retirement Study (HRS) between 1992 and 2014 compare the relationship between different levels and forms of debt and heart attack risk trajectories across four cohorts. Although all cohorts experienced growing household debt, including the increase of both secured and unsecured debt, they nevertheless encountered different economic opportunity structures and crises at sensitive times in their life courses, with implications for heart attack risk trajectories. Results from frailty hazards models reveal that unsecured debt is associated with increased risk of heart attack across all cohorts. Higher levels of housing debt, however, predict higher rates of heart attack among only the earlier cohorts. Heart attack risk trajectories for Baby Boomers with high levels of housing debt are lower than those of same-aged peers with no housing debt. Thus, the relationship between debt and heart attack varies by level and form of debt across cohorts but distinguishes Baby Boomer cohorts based on their diverse exposures to volatile housing market conditions over the sensitive household formation period of the life course.

Sex Differences in Genetic Associations With Longevity.

IMPORTANCE: Sex differences in genetic associations with human longevity remain largely unknown; investigations on this topic are important for individualized health care. OBJECTIVE: To explore sex differences in genetic associations with longevity. DESIGN SETTING AND PARTICIPANTS: This population-based case-control study used sex-specific genome-wide association study and polygenic risk score (PRS) analyses to examine sex differences in genetic associations with longevity. Five hundred sixty-four male and 1614 female participants older than 100 years were compared with a control group of 773 male and 1526 female individuals aged 40 to 64 years. All were Chinese Longitudinal Healthy Longevity Study participants with Han ethnicity who were recruited in 1998 and 2008 to 2014. MAIN OUTCOMES AND MEASURES: Sex-specific loci and pathways associated with longevity and PRS measures of joint effects of sex-specific loci. RESULTS: Eleven male-specific and 11 female-specific longevity loci (P < 10-5) and 35 male-specific and 25 female-specific longevity loci (10-5 ≤ P < 10-4) were identified. Each of these loci's associations with longevity were replicated in north and south regions of China in one sex but were not significant in the other sex (P = .13-.97), and loci-sex interaction effects were significant (P < .05). The associations of loci rs60210535 of the LINC00871 gene with longevity were replicated in Chinese women (P = 9.0 × 10-5) and US women (P = 4.6 × 10-5) but not significant in Chinese and US men. The associations of the loci rs2622624 of the ABCG2 gene were replicated in Chinese women (P = 6.8 × 10-5) and European women (P = .003) but not significant in both Chinese and European men. Eleven male-specific pathways (inflammation and immunity genes) and 34 female-specific pathways (tryptophan metabolism and PGC-1α induced) were significantly associated with longevity (P < .005; false discovery rate < 0.05). The PRS analyses demonstrated that sex-specific associations with longevity of the 4 exclusive groups of 11 male-specific and 11 female-specific loci (P < 10-5) and 35 male-specific and 25 female-specific loci (10-5 ≤P < 10-4) were jointly replicated across north and south discovery and target samples. Analyses using the combined data set of north and south showed that these 4 groups of sex-specific loci were jointly and significantly associated with longevity in one sex (P = 2.9 × 10-70 to 1.3 × 10-39) but not jointly significant in the other sex (P = .11 to .70), while interaction effects between PRS and sex were significant (P = 4.8 × 10-50 to 1.2 × 10-16). CONCLUSION AND RELEVANCE: The sex differences in genetic associations with longevity are remarkable, but have been overlooked by previously published genome-wide association studies on longevity. This study contributes to filling this research gap and provides a scientific basis for further investigating effects of sex-specific genetic variants and their interactions with environment on healthy aging, which may substantially contribute to more effective and targeted individualized health care for male and female elderly individuals.

Correlates of changes in walking during the retirement transition: The Multi-Ethnic Study of Atherosclerosis.

Retirement from employment involves disruption in daily routines and has been associated with positive and negative changes in physical activity. Walking is the most common physical activity among older Americans. The factors that influence changes in walking after retirement are unknown. The study objective was to identify correlates of within-person change in recreational walking (for leisure) and transport walking (to get places) during the retirement transition among a multi-ethnic cohort of adults (N = 928) from six US communities. Correlates were measured at the individual (e.g., gender), interpersonal (e.g., social support), and community (e.g., density of walking destinations) levels at study exams between 2000 and 2012. Comparing pre- and post-retirement measures (average 4.5 years apart), 50% of participants increased recreational walking by 60 min or more per week, 31% decreased by 60 min or more per week, and 19% maintained their recreational walking. Forty-one percent of participants increased transport walking by 60 min or more per week, 40% decreased by 60 min or more per week, and 19% maintained their transport walking after retirement. Correlates differed for recreational and transport walking and for increases compared to decreases in walking. Self-rated health, chronic conditions, and perceptions of the neighborhood walking environment were associated with changes in both types of walking after retirement. Further, some correlates differed by gender and retirement age. Findings can inform the targeting of interventions to promote walking during the retirement transition.

Physical Activity, Sedentary Behavior, and Retirement: The Multi-Ethnic Study of Atherosclerosis.

INTRODUCTION: Physical activity and sedentary behavior are major risk factors for chronic disease. These behaviors may change at retirement, with implications for health in later life. The study objective was to describe longitudinal patterns of moderate to vigorous and domain-specific physical activity and TV watching by retirement status. METHODS: Participants in the Multi-Ethnic Study of Atherosclerosis (n=6,814) were recruited from six U.S. communities and were aged 45-84 years at baseline. Retirement status and frequency and duration of domain-specific physical activity (recreational walking, transport walking, non-walking leisure activity, caregiving, household, occupational/volunteer) and TV watching were self-reported at four study exams (2000 to 2012). Fixed effect linear regression models were used to describe longitudinal patterns in physical activity and TV watching by retirement status overall and stratified by socioeconomic position. Analyses were conducted in 2017. RESULTS: Of 4,091 Multi-Ethnic Study of Atherosclerosis participants not retired at baseline, 1,012 (25%) retired during a median of 9 years follow-up. Retirement was associated with a 10% decrease (95% CI= -15%, -5%) in moderate to vigorous physical activity and increases of 13% to 29% in recreational walking, household activity, and TV watching. Among people of low socioeconomic position, the magnitude of association was larger for moderate to vigorous physical activity. Among people of high socioeconomic position, the magnitude of association was larger for non-walking leisure and household activity. CONCLUSIONS: The retirement transition was associated with changes in physical activity and TV watching. To inform intervention development, future research is needed on the determinants of behavior change after retirement, particularly among individuals of low socioeconomic position.

Race-ethnicity and health trajectories: tests of three hypotheses across multiple groups and health outcomes.

Racial-ethnic disparities in static levels of health are well documented. Less is known about racial-ethnic differences in age trajectories of health. The few studies on this topic have examined only single health outcomes and focused on black-white disparities. This study extends prior research by using a life course perspective, panel data from the Health and Retirement Study, and multilevel growth curve models to investigate racial-ethnic differences in the trajectories of serious conditions and functional limitations among blacks, Mexican Americans, and whites. We test three hypotheses on the nature of racial-ethnic disparities in health across the life course (aging-as-leveler, persistent inequality, and cumulative disadvantage). Results controlling for mortality selection reveal that support for the hypotheses varies by health outcome, racial-ethnic group, and life stage. Controlling for childhood socioeconomic status, adult social and economic resources, and health behaviors reduces but does not eliminate racial-ethnic disparities in health trajectories.

2010 SSS Presidential Address: The Devolution of Risk and the Changing Life Course in the United States.

Recent patterns of labor exit in late life in the United States are increasingly heterogeneous. This heterogeneity stems from diverse employment careers that are emerging in the workplace where job security is declining. Individuals' structural locations in the labor market expose them to diverse risks for employment and income security at older ages. Among those risks are access to institutional mechanisms for retirement saving and the requirement to assume full responsibility for decisions about retirement savings that involve market risks. The spread of these individualized pressures to invest in retirement has elevated the importance of financial literacy in the 21st century. Late employment careers and patterns of financial literacy are studied in this article using the premier U.S. longitudinal dataset from the National Institute of Aging, the Health and Retirement Study initiated in 1992, which is linked to restricted Social Security earnings records that extend over several decades. These merged data afford the opportunity to observe continuous work histories in this sample from 1981 through 2006 to identify latent trajectories of employment in late life. In addition, a supplementary module attached to the 2004 wave of the HRS provides valuable information on the financial literacy of subgroups. The work-retirement trajectories and financial literacy patterns observed reflect persistent patterns of inequality amplified by modern risks in the labor market.

Childhood adversity, educational trajectories, and self-reported health in later life among U.S. women and men at the turn of the century.

A major objective of current life course research is to specify the processes linking early childhood conditions to subsequent life course statuses that span educational, occupational, familial, and health domains across the life span. This study confronts at least two persistent challenges to the rigorous specification of the relationships among these variables. The first is that the point-in-time measurement of education as "years of schooling" masks considerable heterogeneity in the timing and curricular tracks of schooling and obscures our understanding of how and when education matters for life-course inequality. The second challenge involves inter dependencies between aspects of life-course inequality, including educational achievement and health. The intertwining of these variables across the life course, and their usual conceptualization and measurement, limit the interpretation of their relationship and its generalizability across studies. We use data from three waves of the National Survey of Families and Households between 1987-1988 and 2001-2002 to explore trajectories of self-reported health, applying latent class cluster analysis (finite mixture models) to deal directly with these measurement and specification issues. Generally, we find mediating effects of education in mid-to late-life health demonstrating the pivotal role of education in life course processes. Women's childhood backgrounds are more heterogeneous and temporally complex educational careers affect their self-assessed health more than men's. Late degrees are linked to poor health trajectories among women, but not men. Also, marital history, number of births and health behaviors are associated in expected ways with women's and men's health trajectories at midlife.

Gender differences in the link between childhood socioeconomic conditions and heart attack risk in adulthood.

A growing body of evidence shows that childhood socioeconomic status (SES) is predictive of disease risk in later life, with those from the most disadvantaged backgrounds more likely to experience poor adult-health outcomes. Most of these studies, however are based on middle-aged male populations and pay insufficient attention to the pathways between childhood risks and specific adult disorders. This article examines gender differences in the link between childhood SES and heart attack risk trajectories and the mechanisms by which early environments affect future disease risk. By using methods that model both latent and path-specific influences, we identify heterogeneity in early life conditions and human, social, and health capital in adulthood that contribute to diverse heart attack risk trajectories between and among men and women as they age into their 60s and 70s. We find that key risk factors for heart attack operate differently for men and women. For men, childhood SES does not differentiate those at low, increasing, and high risk for heart attack. In contrast, women who grew up without a father and/or under adverse economic conditions are the most likely to experience elevated risk for heart attack, even after we adjust for the unequal distribution of working and living conditions, social relationships, access to health care, and adult lifestyle behaviors that influence health outcomes.

Processes of cumulative adversity: childhood disadvantage and increased risk of heart attack across the life course.

OBJECTIVES: This article examines how processes of cumulative adversity shape heart attack risk trajectories across the life course. METHODS: Our sample includes 9,760 Health and Retirement Study respondents born between 1931 and 1941. Using self-reported retrospective measures of respondents' early background, we first identify three latent classes with differential exposure to childhood disadvantage. Intervening covariates associated with educational attainment, employment status, income attainment, marital history, and health behaviors are added to capture sequential processes of adversity. Final latent-class cluster models estimate the cumulative impact of these covariates on three different heart attack risk trajectories between 1992 and 2002: high, increasing, and low. RESULTS: Early disadvantage and childhood illness have severe enduring effects and increase the risk for heart attack. Adult pathways, however, differentially influence trajectories of heart attack risk and mediate the effects of early disadvantage. DISCUSSION: Findings suggest that future research should consider how processes of cumulative adversity initiated in childhood influence health outcomes in older ages.