BACKGROUND:Evidence suggested that abiotic airborne exposures may be associated with changes in body composition. However, more evidence is needed to identify key pollutants linked to adverse health effects and their underlying biomolecular mechanisms, particularly in sensitive older adults. OBJECTIVES:Our research aimed to systematically assess the relationship between abiotic airborne exposures and changes in body composition among healthy older adults, as well as the potential mediating mechanisms through the serum lipidome. METHODS:From September 2018 to January 2019, we conducted a monthly survey among 76 healthy adults (60-69 years old) in the China Biomarkers of Air Pollutant Exposure (BAPE) study, measuring their personal exposures to 632 abiotic airborne pollutions using MicroPEM and the Fresh Air wristband, 18 body composition indicators from the InBody 770 device, and lipidomics from venous blood samples. We used an exposome-wide association study (ExWAS) and deletion/substitution/addition (DSA) model to unravel complex associations between exposure to contaminant mixtures and body composition, a Bayesian kernel machine regression (BKMR) model to assess the overall effect of key exposures on body composition, and mediation analysis to identify lipid intermediators. RESULTS:The ExWAS and DSA model identified that 2,4,5-T methyl ester (2,4,5-TME), 9,10-Anthracenedione (ATQ), 4b,8-dimethyl-2-isopropylphenanthrene, and 4b,5,6,7,8,8a,9,10-octahydro-(DMIP) were associated with increased body fat mass (BFM), fat mass indicators (FMI), percent body fat (PBF), and visceral fat area (VFA) in healthy older adults [Bonferroni-Hochberg false discovery rate (FDRBH)<0.05]. The BKMR model demonstrated a positive correlation between contaminants (anthracene, ATQ, copaene, di-epi-α-cedrene, and DMIP) with VFA. Mediation analysis revealed that phosphatidylcholine [PC, PC(16:1e/18:1), PC(16:2e/18:0)] and sphingolipid [SM, SM(d18:2/24:1)] mediated a significant portion, ranging from 12.27% to 26.03% (p-value <0.05), of the observed increase in VFA. DISCUSSION:Based on the evidence from multiple model results, ATQ and DMIP were statistically significantly associated with the increased VFA levels of healthy older adults, potentially regulated through lipid intermediators. These findings may have important implications for identifying potentially harmful environmental chemicals and developing targeted strategies for the control and prevention of chronic diseases in the future, particularly as the global population is rapidly aging. https://doi.org/10.1289/EHP13865.

Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants’ pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.

BACKGROUND AND AIMS:Emerging evidence has raised an obesity paradox in observational studies of body mass index (BMI) and health among the oldest-old (aged ≥80 years), as an inverse relationship of BMI with mortality was reported. This study was to investigate the causal associations of BMI, waist circumference (WC), or both with mortality in the oldest-old people in China. METHODS:A total of 5306 community-based oldest-old (mean age 90.6 years) were enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 1998 and 2018. Genetic risk scores were constructed from 58 single-nucleotide polymorphisms (SNPs) associated with BMI and 49 SNPs associated with WC to subsequently derive causal estimates for Mendelian randomization (MR) models. One-sample linear MR along with non-linear MR analyses were performed to explore the associations of genetically predicted BMI, WC, and their joint effect with all-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. RESULTS:During 24 337 person-years of follow-up, 3766 deaths were documented. In observational analyses, higher BMI and WC were both associated with decreased mortality risk [hazard ratio (HR) 0.963, 95% confidence interval (CI) 0.955-0.971 for a 1-kg/m2 increment of BMI and HR 0.971 (95% CI 0.950-0.993) for each 5 cm increase of WC]. Linear MR models indicated that each 1 kg/m2 increase in genetically predicted BMI was monotonically associated with a 4.5% decrease in all-cause mortality risk [HR 0.955 (95% CI 0.928-0.983)]. Non-linear curves showed the lowest mortality risk at the BMI of around 28.0 kg/m2, suggesting that optimal BMI for the oldest-old may be around overweight or mild obesity. Positive monotonic causal associations were observed between WC and all-cause mortality [HR 1.108 (95% CI 1.036-1.185) per 5 cm increase], CVD mortality [HR 1.193 (95% CI 1.064-1.337)], and non-CVD mortality [HR 1.110 (95% CI 1.016-1.212)]. The joint effect analyses indicated that the lowest risk was observed among those with higher BMI and lower WC. CONCLUSIONS:Among the oldest-old, opposite causal associations of BMI and WC with mortality were observed, and a body figure with higher BMI and lower WC could substantially decrease the mortality risk. Guidelines for the weight management should be cautiously designed and implemented among the oldest-old people, considering distinct roles of BMI and WC.

BACKGROUND:Environmental contaminants (ECs) are increasingly recognized as crucial drivers of dyslipidemia and cardiovascular disease (CVD), but the comprehensive impact spectrum and interlinking mechanisms remain uncertain. OBJECTIVES:We aimed to systematically evaluate the association between exposure to 80 ECs across seven divergent categories and markers of dyslipidemia and investigate their underpinning biomolecular mechanisms via an unbiased integrative approach of internal chemical exposome and multi-omics. METHODS:A longitudinal study involving 76 healthy older adults was conducted in Jinan, China, and participants were followed five times from 10 September 2018 to 19 January 2019 in 1-month intervals. A broad spectrum of seven chemical categories covering the prototypes and metabolites of 102 ECs in serum or urine as well as six serum dyslipidemia markers [total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein (Apo)A1, ApoB, and ApoE4] were measured. Multi-omics, including the blood transcriptome, serum/urine metabolome, and serum lipidome, were profiled concurrently. Exposome-wide association study and the deletion/substitution/addition algorithms were applied to explore the associations between 80 EC exposures detection frequency >50% and dyslipidemia markers. Weighted quantile sum regression was used to assess the mixture effects and relative contributions. Multi-omics profiling, causal inference model, and pathway analysis were conducted to interpret the mediating biomolecules and underlying mechanisms. Examination of cytokines and electrocardiograms was further conducted to validate the observed associations and biomolecular pathways. RESULTS:Eight main ECs [1-naphthalene, 1-pyrene, 2-fluorene, dibutyl phosphate, tri-phenyl phosphate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, chromium, and vanadium] were significantly associated with most dyslipidemia markers. Multi-omics indicated that the associations were mediated by endogenous biomolecules and pathways, primarily pertinent to CVD, inflammation, and metabolism. Clinical measures of cytokines and electrocardiograms further cross-validated the association of these exogenous ECs with systemic inflammation and cardiac function, demonstrating their potential mechanisms in driving dyslipidemia pathogenesis. DISCUSSION:It is imperative to prioritize mitigating exposure to these ECs in the primary prevention and control of the dyslipidemia epidemic. https://doi.org/10.1289/EHP13864.

Objective: To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults. Methods: In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Results: Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the M (Q1, Q3) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an M (Q1, Q3) of 1.27 (0.64, 2.50) ng/ml. The M (Q1, Q3) for TSH, T3, and T4 was 3.74 (2.55, 5.69) μIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95%CI:-15.17%, -4.36%) and 11.14% (95%CI:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Conclusion: Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.

This study aimed to examine the impact of greenness and fine particulate matter <2.5 μm (PM2.5) on overweight/obesity among older adults in China.

Background The association between fine particular matter (PM2.5) and frailty is less studied, and the national burden of PM2.5-related frailty in China is unknown. Objective To explore the association between PM2.5 exposure and incident frailty in older adults, and estimate the corresponding disease burden. Design Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. Setting Twenty-three provinces in China. Subjects A total of 25,047 participants aged >= 65-year-old. Methods Cox proportional hazards models were performed to evaluate the association between PM2.5 and frailty in older adults. A method adapted from the Global Burden of Disease Study was used to calculate the PM2.5-related frailty disease burden. Results A total of 5,733 incidents of frailty were observed during 107,814.8 person-years follow-up. A 10 mu g/m(3) increment of PM2.5 was associated with a 5.0% increase in the risk of frailty (Hazard Ratio = 1.05, 95% confidence interval = [1.03-1.07]). Monotonic, but non-linear exposure-response, relationships of PM2.5 with risk of frailty were observed, and slopes were steeper at concentrations >50 mu g/m(3). Considering the interaction between population ageing and mitigation of PM2.5, the PM2.5-related frailty cases were almost unchanged in 2010, 2020 and 2030, with estimations of 664,097, 730,858 and 665,169, respectively. Conclusions This nation-wide prospective cohort study showed a positive association between long-term PM2.5 exposure and frailty incidence. The estimated disease burden indicated that implementing clean air actions may prevent frailty and substantially offset the burden of population ageing worldwide.

Objective: To investigate the association of mixed exposure to greenness and nitrogen dioxide(NO2) and hypertension among the older adults aged 65 years and over in China. Methods: The study subjects were from the Chinese Longitudinal Healthy Longevity Survey from 2017 to 2018. A total of 15 423 older adults aged 65 years and over meeting the criteria were finally included in the study. A questionnaire survey was used to collect information on demographic characteristics, lifestyle habits and self-reported prevalence of hypertension. Blood pressure values were obtained through physical examination. The level of normalized difference vegetation index(NDVI) was measured by the Medium-resolution Imaging Spectral Radiator(MODIS) of the National Aeronautics and Space Administration(NASA). The concentration of NO2 was from China's surface air pollutant data set. Meteorological data was from NASA MERRA-2. The exposure to NDVI and NO2 for each study subject was calculated based on the area within a 1 km radius around their residence. The association between mixed exposure of NDVI and NO2 as well as their interaction and hypertension in older adults was analyzed by using the multivariate logistic regression model. The restrictive cubic spline(RCS) function was used to explore the exposure-response relationship between greenness and NO2 and the risk of hypertension in study subjects. Results: The mean age of 15 423 older adults were (85.6±11.6). Women accounted for 56.3%(8 685/15 423) and 55.6%(8 578/15 423) lived in urban areas. The mean time of residence was (60.9±28.5) years. 59.8% of participants were with hypertension. The mean NDVI level was 0.41±0.13, and the mean NO2 concentration was (32.18±10.36) μg/cm3. The results of multivariate logistic regression analysis showed that NDVI was inversely and linearly associated with the hypertension in older adults, with the OR(95%CI) value of 0.959(0.928-0.992). Compared with the T1 group of NDVI, the risk of hypertension was lower in the T3 group, with the OR(95%CI) value of 0.852(0.769-0.944), and the trend test was statistically significant(P<0.05). Compared with the T1 group of NO2, the risk of hypertension was higher in the T2 and T3 groups, with OR(95%CI) values of 1.160(1.055-1.275) and 1.244(1.111-1.393), and the trend test was statistically significant (P<0.05). The result of the RCS showed that NDVI was inversely and linearly associated with hypertension in older adults. NO2 was nonlinearly associated with hypertension in older adults. The interaction analysis showed that NDVI and NO2 had a negative multiplicative interaction on the risk of hypertension, with OR(95%CI) value of 0.995(0.992-0.997). Conclusion: Exposure to greenness and NO2 are associated with hypertension in older adults.

Objective:To analyze the short-term effect of individual atmospheric PM 2.5 exposure on the diversity, enterotype, and community structure of gut microbiome in healthy elderly people in Jinan, Shandong province. Methods:The present panel study recruited 76 healthy elderly people aged 60-69 years old in Dianliu Street, Lixia District, Jinan, Shandong Province, and followed them up five times from September 2018 to January 2019. The relevant information was collected by questionnaire, physical examination, precise monitoring of individual PM 2.5 exposure, fecal sample collection and gut microbiome 16S rDNA sequencing. The Dirichlet multinomial mixtures (DMM) model was used to analyze the enterotype. Linear mixed effect model and generalized linear mixed effect model were used to analyze the effect of PM 2.5 exposure on gut microbiome α diversity indices (Shannon, Simpson, Chao1, and ACE indices), enterotype and abundance of core species. Results:Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 352 person-visits. The age of 76 subjects was (65.0±2.8) years old with BMI (25.0±2.4) kg/m 2. There were 38 males accounting for 50% of the subjects. People with an educational level of primary school or below accounted for 10.5% of the 76 subjects, and those with secondary school and junior college or above accounting for 71.1% and 18.4%. The individual PM 2.5 exposure concentration of 76 subjects during the study period was (58.7±53.7) μg/m 3. DMM model showed that the subjects could be divided into four enterotypes, which were mainly driven by Bacteroides, Faecalibacterium, Lachnospiraceae, Prevotellaceae, and Ruminococcaceae. Linear mixed effects model showed that different lag periods of PM 2.5 exposure were significantly associated with a lower gut α diversity index (FDR <0.05 after correction). Further analysis showed that PM 2.5 exposure was significantly associated with changes in the abundances of Firmicutes ( Megamonas, Blautia, Streptococcus, etc.) and Bacteroidetes ( Alistipes) (FDR<0.05 after correction). Conclusion:Short-term PM 2.5 exposure is significantly associated with a decrease in gut microbiome diversity and changes in the abundance of several species of Firmicutes and Bacteroidetes in the elderly. It is necessary to further explore the underlying mechanisms between PM 2.5 exposure and the gut microbiome, so as to provide a scientific basis for promoting the intestinal health of the elderly.

BACKGROUND AND AIM: Studies have linked elevations in short-term ozone exposure to acute adverse health outcomes. In this study, we aimed to explore whether long-term ozone exposure was linked to the development of frailty in older adults. METHODS: A total of 15,734 participants aged ≥65-year-old and were free of frailty were included in Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2005 to 2018. Frailty was defined by a frailty index (FI) ≥0.25, which was measured by 39 health deficits. Personal ozone exposures were estimated using full-composition annual ozone covering all of China at a 0.05° resolution. County-level ozone-related burden of frailty in China was calculated by warm season hazard ratio of frailty. RESULTS: During 78,588 person-years follow-up, 3587 incident frailties were documented. In competing risk models, each 10-μg/m³ increase in baseline warm-season (May to October) and yearly ozone exposure corresponded to 6.9% and 12.1% higher risk of incident frailty, the hazard ratios were 1.069 (1.035-1.104) and 1.121 (1.063-1.182), respectively. Monotonically increasing dose-response of warm-season and yearly ozone exposure with incident frailty and FI score were observed. With the dramatic population aging and increasing ozone exposure simultaneously in China, it was estimated that the burden of warm season ozone related incident frailty among the population aged ≥65-year-old in China were 1,818,729 and 3,700,237 cases in 2010 and 2020, respectively, and there will be 4,806,037 incident frailties in 2030. CONCLUSIONS: This nationwide prospective cohort study established that long-term ozone exposure was associated with incident frailty and contributed to an enormously significant and increased disease burden for the older adults, suggesting that controlling ozone exposure may be a priority area for air quality regulations in China in next decade that may yield substantial health benefits. KEYWORDS: ozone; older adults; frailty; CLHLS; disease burden

Lead (Pb) is a widespread environmental contaminant, associated with a higher risk of functional impairment that can lead to frailty in older adults. However, few studies focused on the association of Pb exposure with frailty among the oldest old (aged ≥ 80 years). In this study, we aimed to assess the associations of Pb with frailty and its components in the oldest old. The included individuals were the oldest old aged ≥ 80 years who participated in a 2017 cross-sectional survey of the Healthy Aging and Biomarkers Cohort Study. Frailty was ascertained by the frailty index, which was created based on health deficits. We used logistic regression models to estimate the association of blood Pb with frailty and its components. The geometric mean and median of blood Pb were 38.51 μg/L and 36.27 μg/L among the oldest old, respectively. Compared with the first quartile of blood Pb, participants in the fourth quartile had higher risk of frailty and its components, the ORs are 1.71 (1.22-2.41), 1.99 (1.35-2.94), 1.91 (1.25-2.93), 1.57 (1.13-2.17) and 1.43 (1.05-1.96), for frailty, ADL disability, IADL disability, functional limitations, and hearing loss in the oldest old, respectively. There was a significant interaction between blood Pb and frailty in different age groups. In conclusion, our findings provide preliminary evidence that higher blood Pb may increase the risk of frailty among the oldest old by increasing the risk of disability in four physical functions: disability in ADL, disability in IADL, functional limitations, and hearing loss.

目的 探讨中国长寿地区65岁及以上老年人血硒水平与虚弱患病风险的关系.方法 数据来源于"老年健康生物标志物队列研究"项目,以2017-2018年调查的中国9个长寿地区2 464名65岁及以上老年人为研究对象,通过问卷调查获得调查对象的人口学特征、生活方式、饮食习惯及健康状况等信息,同时使用虚弱指数量表评定调查对象的虚弱程度,收集空腹静脉血,以电感耦合等离子体质谱法检测硒的内暴露水平.根据血硒水平的四分位数将研究对象分为4组(Q1～Q4组),采用多因素Logistic回归模型分析血硒水平与虚弱的关系,采用限制性立方样条模型研究血硒水平与虚弱之间的暴露反应关系.结果 2 464名研究对象年龄为(84.55±11.38)岁,其中男性1 180名(47.89％),女性1 284名(52.11％);非虚弱者1 866名(75.73％),虚弱者为598名(24.27％).男性和女性血硒水平的几何均数分别为109.73和108.33 μg/L;(65～79)、(80～89)、(90～99)和≥100岁老年人血硒水平的几何均数分别为119.15、106.54、102.12、98.04 μg/L.采用多因素Logis-tic回归模型调整相关混杂因素后,与血硒水平Q1组老年人相比,血硒水平较高者虚弱的患病风险较低,Q2,Q3,Q4组的OR(95％CI)值分别为0.68(0.49～0.96)、0.65(0.46～0.92)和0.59(0.40～0.87).限制性立方样条模型分析显示,血硒水平与老年人虚弱的患病风险呈非线性暴露反应关系(P非线性＜0.01).结论 我国9个长寿地区65岁及以上老年人血硒水平与虚弱患病风险存在负向关联.