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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.

The social gradient in health – that individuals with lower SES have worse health than those with higher SES– is welldocumented using self-reports of health in more developed countries. Less is known about the relationship between SES and health biomarkers among older adults residing in less developed countries. We use data from the ChineseLongitudinal Healthy Longevity Survey (CLHLS) longevity areas sub-sample to examine the social gradient in healthamong rural young-old and oldest-old adults (N=2,121). Our health indicators include individual biomarkers, metabolic syndrome, and self-reports of health. We found a largely positive relationship between SES and health. SES was more consistently associated with individual biomarkers among the oldest-old than the young-old, providing evidence for cumulative disadvantage. We discuss the implications of our findings for older adults who have lived through different social, economic, and health regimes.

Summary: Background: Evidence from cohort studies in North America and Europe indicates that long-term exposure to fine particulate matter (PM2·5) is associated with an increased mortality risk. However, this association has rarely been quantified at higher ambient concentrations. We estimated the hazard ratio (HR) for all-cause mortality from long-term exposure to PM2·5 in a well established Chinese cohort of older adults. Methods: The Chinese Longitudinal Healthy Longevity Survey (CLHLS) is a prospective cohort study of men and women aged 65 years and older enrolled in 2008 and followed up through 2014 for mortality events. We studied individuals for whom residential locations were available in 2008 for linkage to 1 km grids of PM2·5 concentrations, derived from satellite remote sensing. Cox proportional hazards models were used to estimate the effect of long-term exposure to PM2·5 on all-cause mortality, controlling for age, sex, smoking status, drinking status, physical activity, body-mass index, household income, marital status, and education. We then used our results to estimate premature mortality related to PM2·5 exposure in the population aged 65 years and older in China in 2010. Findings: 13 344 individuals in the CLHLS cohort had data for all timepoints, yielding follow-up data for 49 440 person-years. In a 3-year window, these individuals were exposed to a median PM2·5 concentration of 50·7 μg/m3 (range 6·7–113·3). The overall HR for a 10 μg/m3 increase in this value was 1·08 (95% CI 1·06–1·09). In stratified analyses, HRs were higher in rural than in urban locations, in southern versus northern regions, and with exposure to lower versus higher PM2·5 concentrations. Based on the overall HR, we estimated that 1 765 820 people aged 65 years and older in China in 2010 had premature mortality related to PM2·5 exposure. Interpretation: Long-term exposure to PM2·5 is associated with an increased risk of all-cause mortality among adults aged 65 years and older in China, but the magnitude of the risk declines as the concentration of PM2·5 increases. Funding: National Natural Science Foundation of China, National High-Level Talents Special Support Plan of China for Young Talents, US National Aeronautics and Space Administration, and the Columbia University Global Policy Initiative.