A Novel Metabolomic Aging Clock Predicting Health Outcomes and Its Genetic and Modifiable Factors.

Existing metabolomic clocks exhibit deficiencies in capturing the heterogeneous aging rates among individuals with the same chronological age. Yet, the modifiable and non-modifiable factors in metabolomic aging have not been systematically studied. Here, a new aging measure-MetaboAgeMort-is developed using metabolomic profiles from 239,291 UK Biobank participants for 10-year all-cause mortality prediction. The MetaboAgeMort showed significant associations with all-cause mortality, cause-specific mortality, and diverse incident diseases. Adding MetaboAgeMort to a conventional risk factors model improved the predictive ability of 10-year mortality. A total of 99 modifiable factors across seven categories are identified for MetaboAgeMort. Among these, 16 factors representing pulmonary function, body composition, socioeconomic status, dietary quality, smoking status, alcohol intake, and disease status showed quantitatively stronger associations. The genetic analyses revealed 99 genomic risk loci and 271 genes associated with MetaboAgeMort. The tissue-enrichment analysis showed significant enrichment in liver. While the external validation of the MetaboAgeMort is required, this study illuminates heterogeneous metabolomic aging across the same age, providing avenues for identifying high-risk individuals, developing anti-aging therapies, and personalizing interventions, thus promoting healthy aging and longevity.

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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.

Moderate BMI accumulation modified associations between blood benzene, toluene, ethylbenzene and xylene (BTEX) and phenotypic aging: mediating roles of inflammation and oxidative stress.

The associations between blood benzene, toluene, ethylbenzene, and xylenes (BTEX) and biological aging among general adults remain elusive. The present study comprised 5780 participants from the National Health and Nutrition Examination Survey 1999-2010. A novel measure of biological aging, phenotypic age acceleration (PhenoAge.Accel), derived from biochemical markers was calculated. Weighted generalized linear regression and weighted quantile sum regression (WQS) were utilized to assess the associations between BTEX components and mixed exposure, and PhenoAge.Accel. The mediating roles of systemic immune-inflammation index (SII) and oxidative stress indicators (serum bilirubin and gamma-glutamyl transferase), along with the modifying effects of body mass index (BMI) were also examined. In the single-exposure model, the highest quantile of blood benzene (b = 0.89, 95%CI: 0.58 to 1.20), toluene (b = 0.87, 95%CI: 0.52 to 1.20), and ethylbenzene (b = 0.80, 95%CI: 0.46 to 1.10) was positively associated with PhenoAge.Accel compared to quantile 1. Mixed-exposure analyses revealed a consistent positive association between BTEX mixed exposure and PhenoAge.Accel (b = 0.88, 95%CI: 0.56 to 1.20), primarily driven by benzene (92.78%). The association between BTEX and PhenoAge.Accel was found to be partially mediated by inflammation and oxidative stress indicators (ranging from 3.2% to 13.7%). Additionally, BMI negatively modified the association between BTEX mixed exposure and PhenoAge.Accel, with a threshold identified at 36.2 kg/m^2. Furthermore, BMI negatively moderated the direct effect of BTEX mixed exposure on PhenoAge.Accel in moderated mediation models, while positively modified the link between SII and PhenoAge.Accel in the indirect path (binteraction = 0.04, 95%CI: 0.01 to 0.06). Overall, BTEX mixed exposure was associated with PhenoAge.Accel among US adults, with benzene may have reported most contribution, and inflammation and oxidative damage processes may partially explain this underlying mechanism. The study also highlighted the potential benefits of appropriate BMI increased. Additional large-scale cohort studies and experiments were necessary to substantiate these findings.

Age, sex, and APOE gene-specific associations between dynapenic obesity and dementia in a large cohort.

OBJECTIVE: To investigate the associations between dynapenic obesity and the risk of dementia, and the modifying effects of age, sex, and the APOE gene, using a large population-based cohort. METHODS: 279,884 participants aged 55 and above from the UK Biobank were included. The participants were classified into four categories based on body mass index and hand grip strength: healthy, obesity, dynapenia, and dynapenic obesity. The incident dementia was identified based on linked hospital records and death register data. Cox proportional hazards regression models were used to estimate the associations, followed by age-, sex-, and apolipoprotein E (APOE) gene-stratified analyses. RESULTS: During the median follow-up of 12.4 years, 5,170 (1.8%) participants developed dementia. Compared with the healthy group, participants with dynapenic obesity had 67% higher dementia risk (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.44-1.94). Compared with the healthy group, higher risks of dementia in participants with dynapenic obesity were respectively observed in male (HR: 2.03, 95% CI: 1.65-2.50), younger (<65 years, HR: 1.97, 95% CI: 1.55-2.50), and non-ε4-carrier (HR: 1.97, 95% CI: 1.60-2.44) (all P for interaction <0.05). In participants under 65 years and non-ε4-carrier, those with dynapenic obesity had the highest risk of dementia (HR: 2.63, 95% CI: 1.91-3.62), compared with the healthy group (P for second order interaction = 0.026). CONCLUSIONS: Dynapenic obesity is associated with increased risks of dementia, especially in participants under 65 years and non-ε4-carrier, suggesting the importance of managing dynapenic obesity in the prevention of cognition-related disorders.

Heterogeneous associations of multiplexed environmental factors and multidimensional aging metrics.

Complicated associations between multiplexed environmental factors and aging are poorly understood. We manipulated aging using multidimensional metrics such as phenotypic age, brain age, and brain volumes in the UK Biobank. Weighted quantile sum regression was used to examine the relative individual contributions of multiplexed environmental factors to aging, and self-organizing maps (SOMs) were used to examine joint effects. Air pollution presented a relatively large contribution in most cases. We also found fair heterogeneities in which the same environmental factor contributed inconsistently to different aging metrics. Particulate matter contributed the most to variance in aging, while noise and green space showed considerable contribution to brain volumes. SOM identified five subpopulations with distinct environmental exposure patterns and the air pollution subpopulation had the worst aging status. This study reveals the heterogeneous associations of multiplexed environmental factors with multidimensional aging metrics and serves as a proof of concept when analyzing multifactors and multiple outcomes.

Functional disability and receipt of informal care among Chinese adults living alone with cognitive impairment.

BACKGROUND: Adults with cognitive impairment are prone to living alone in large numbers but receive relatively little attention. This study aimed to evaluate whether living alone with cognitive impairment was associated with a higher burden of functional disability but lack of informal care. METHODS: 982 observations of adults living alone with cognitive impairment and 50,695 observations of adults living with others and with normal cognition were identified from 4 waves (2011/2012, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study (CHARLS). A matched comparator was selected using propensity score matching (1:2). Functional disability included disability in Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), and mobility. The time of receiving informal care was measured in monthly hours. RESULTS: Adults living alone with cognitive impairment demonstrated significantly higher odds ratio of ADL disability (OR = 1.59, 95 % CI: 1.30, 1.95), IADL disability (OR = 1.19, 95 % CI: 1.00, 1.44), mobility disability (OR = 1.38, 95 % CI: 1.12, 1.70), but received fewer hours of informal care (ß = -127.7 h per month, standard error = 25.83, P < 0.001), compared to the adults living with others and with normal cognition. CONCLUSIONS: This study highlights the high burden of functional disability but low coverage of informal care among Chinese adults living alone with cognitive impairment and calls for more resources to be allocated to this vulnerable subpopulation to improve the functional health and to increase the provision of long-term care services.

Impact of sarcopenic obesity on heart failure in people with type 2 diabetes and the role of metabolism and inflammation: A prospective cohort study.

AIMS: We aimed to prospectively evaluate the association of sarcopenic obesity (SO) with the incidence risk of heart failure (HF), and the mediating role of metabolomics and inflammation in people with type 2 diabetes (T2D). METHODS: 22,496 participants with T2D from the UK Biobank were included. SO was defined as the combination of obesity (body mass index ≥30 kg/m2) and sarcopenia (grip strength <27 kg in male or <16 kg in female). The incident HF was identified through linked hospital records. Cox proportional hazard regression models were used to estimate the associations. Mediation analysis was conducted to evaluate the mediating effect of the "metabolomic risk score" of HF, which was derived from 168 plasma metabolites through LASSO regression, and five inflammatory markers (e.g., C-reactive protein [CRP] level) on the aforementioned associations. RESULTS: 1946 (8.7 %) participants developed HF during a median follow-up of 12.0 years. Compared to participants with neither obesity nor sarcopenia, those with obesity & non-sarcopenia (hazard ratio [HR]: 1.80, 95 % confidence interval [CI]: 1.62, 2.00), sarcopenia & non-obesity (HR: 1.90, 95 % CI: 1.56, 2.31) and SO (HR: 2.29, 95 % CI: 1.92, 2.73) showed a higher risk of HF. The metabolomic risk score (20.0 %) and CRP (20.4 %) meditated this association. CONCLUSIONS: SO was associated with an increased risk of HF in people with T2D and metabolomics and inflammation partially mediated this association. Our findings suggest the importance of managing obesity and muscle strength simultaneously in preventing HF among people with T2D and shed light on the underlying mechanisms.

Sex-Specific Association Between Childhood Adversity and Accelerated Biological Aging.

Is childhood adversity associated with biological aging, and if so, does sex modify the association, and do lifestyle and mental health mediate the association? A lifespan analysis is conducted using data on 142 872 participants from the UK Biobank to address these questions. Childhood adversity is assessed through the online mental health questionnaire (2016), including physical neglect, physical abuse, emotional neglect, emotional abuse, sexual abuse, and a cumulative score. Biological aging is indicated by telomere length (TL) measured from leukocyte DNA using qPCR, and the shorter TL indicates accelerated biological aging; a lifestyle score is constructed using body mass index, physical activity, drinking, smoking, and diet; mental disorder is assessed using depression, anxiety, and insomnia at the baseline survey. The results reveal a sex-specific association such that childhood adversity is associated with shorter TL in women after adjusting for covariates including polygenic risk score for TL, but not in men. Unhealthy lifestyle and mental disorder partially mediate the association in women. The proportions of indirect effects are largest for sexual and physical abuse. These findings highlight the importance of behavioral and psychological interventions in promoting healthy aging among women who experienced childhood adversity, particularly sexual and physical abuse.

The effect of weighted blankets on sleep and related disorders: a brief review.

Background: Sleep disorders such as insomnia can lead to a range of health problems. The high risk of side effects and drug abuse of traditional pharmacotherapy calls for a safer non-pharmacotherapy. Aims: To examine the use and efficacy of weighted blankets in improving sleep and related disorders in different populations and explore the possible mechanisms. Methods: A literature search was conducted using PubMed, Embase, Web of Science, MEDLINE, Cochrane Library and CNKI databases. Eligible studies included an intervention with weighted blankets and outcomes covering sleep and/or related disorders (behavioral disturbance, negative emotions and daytime symptoms). Studies using other deep pressure, compression, or exercise-related interventions were excluded. Conclusions: Most of the included studies showed that weighted blankets could effectively improve sleep quality and alleviate negative emotions and daytime symptoms in patients with sleep disorders, attention deficit hyperactivity disorder, autism spectrum disorder, and other related disorders, with a possible mechanism of deep pressure touch. Recommendations: Weighted blankets might be a promising tool for sleep interventions among individuals with sleep disorders in clinical settings. More high-quality and large-scale randomized controlled trials are needed to further validate the safety and efficacy of weighted blankets and explore precise mechanisms.

Healthy Lifestyle and the Risk of Metabolic Dysfunction-Associated Fatty Liver Disease: A Large Prospective Cohort Study.

BACKGRUOUND: The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD. METHODS: A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors. RESULTS: The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle. CONCLUSION: Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Associations of perceived stress with loneliness and depressive symptoms: the mediating role of sleep quality.

BACKGROUND: Whether perceived stress is associated with loneliness and depressive symptoms in general adults, and to what extent sleep quality mediates the associations, remains unknown. The aim of this study was to estimate the associations of perceived stress with loneliness and depressive symptoms, and the mediating role of sleep quality in these associations. METHODS: Cross-sectional data on 734 participants (aged 18-87 years) were analyzed. Perceived stress was assessed using the 10-item Perceived Stress Scale (PSS-10; range 0-40). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI; range 0-21). Loneliness was assessed using the three-item short form of the Revised University of California, Los Angeles (UCLA) loneliness scale (range 3-9). Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression (CESD-10) Scale (range 0-30). General linear regression models, multivariable logistic regression models, and formal mediation analysis were performed. RESULTS: After adjustment for age and sex, we found that with each 1-point increment in the perceived stress score, both the loneliness score (ß = 0.07; 95% confidence interval [CI]: 0.06, 0.08) and depression score (ß = 0.45; 95% CI: 0.40, 0.49) increased significantly. Robust results were observed when adjusting for more confounders. Furthermore, sleep quality mediated 5.3% (95% CI: 1.3%, 10.0%; P = 0.014) and 9.7% (95% CI: 6.2%, 14.0%; P < 0.001) of the associations of perceived stress score with loneliness score and depression score, respectively. CONCLUSIONS: In general Chinese adults, perceived stress was positively associated with loneliness and depressive symptoms, and sleep quality partially mediated these associations. The findings reveal a potential pathway from perceived stress to mental health through sleep behaviors, and highlight the importance of implementing sleep intervention programs for promoting mental health among those who feel highly stressed.

Trajectories of Body Mass Index and Waist Circumference in Relation to the Risk of Cardiac Arrhythmia: A Prospective Cohort Study.

BACKGROUND: The aim of the current study was to explore the trajectories, variabilities, and cumulative exposures of body mass index (BMI) and waist circumference (WC) with cardiac arrhythmia (CA) risks. METHODS: In total, 35,739 adults from the Kailuan study were included. BMI and WC were measured repeatedly during the 2006-2010 waves. CA was identified via electrocardiogram diagnosis. BMI and WC trajectories were fitted using a group-based trajectory model. The associations were estimated using Cox proportional hazards models. RESULTS: We identified four stable trajectories for BMI and WC, respectively. Neither the BMI trajectories nor the baseline BMI values were associated with the risk of CA. Compared to the low-stable WC group, participants in the high-stable WC group had a higher risk of CA (hazard ratio (HR) = 1.40, 95% confidence interval (CI): 1.06, 1.86). Interestingly, the cumulative exposures of BMI and WC instead of their variabilities were associated with the risk of CA. In the stratified analyses, the positive associations of the high-stable WC group with the risk of CA were found in females only (HR = 1.98, 95% CI: 1.02, 3.83). CONCLUSIONS: A high-stable WC trajectory is associated with a higher risk of CA among Chinese female adults, underscoring the potential of WC rather than BMI to identify adults who are at risk.

Influencing Factors of Healthy Aging Risk Assessed Using Biomarkers: A Life Course Perspective.

Assessing individual risks of healthy aging using biomarkers and identifying associated factors have become important areas of research. In this study, we conducted a literature review of relevant publications between 2018 and 2023 in both Chinese and English databases. Previous studies have predominantly used single biomarkers, such as C-reactive protein, or focused on specific life course stages and factors such as socioeconomic status, mental health, educational levels, and unhealthy lifestyles. By summarizing the progress in this field, our study provides valuable insights and future directions for promoting healthy aging from a life course perspective.

Dietary patterns, metabolomics and frailty in a large cohort of 120 000 participants.

Objective: To examine the associations of dietary patterns with frailty and whether metabolic signatures (MSs) mediate these associations. Methods: We used UK Biobank data to examine (1) the associations of four dietary patterns (i.e., alternate Mediterranean diet [aMED], Recommended Food Score [RFS], Dietary Approaches to Stop Hypertension [DASH] and Mediterranean-DASH Intervention for Neurodegenerative Delay [MIND] diet) with frailty (measured by the frailty phenotype and the frailty index) using multivariable logistic regression (analytic sample 1: N = 124 261; mean age = 57.7 years), and (2) the mediating role of MSs (weighted sums of the metabolites selected from 168 plasma metabolites using the LASSO algorithm) in the above associations via mediation analysis (analytic sample 2: N = 26 270; mean age = 57.7 years). Results: Four dietary patterns were independently associated with frailty (all P < 0.001). For instance, compared to participants in the lowest tertile for RFS, those in the intermediate (odds ratio [OR]: 0.81; 95% confidence interval [CI]: 0.74, 0.89) and highest (OR: 0.62; 95% CI: 0.56, 0.68) tertiles had a lower risk of frailty. We found that 98, 68, 123 and 75 metabolites were associated with aMED, RFS, DASH and MIND, respectively, including 16 common metabolites (e.g., fatty acids, lipoproteins, acetate and glycoprotein acetyls). The MSs based on these metabolites partially mediated the association of the four dietary patterns with frailty, with the mediation proportion ranging from 26.52% to 45.83%. The results were robust when using another frailty measure, the frailty index. Conclusions: The four dietary patterns were associated with frailty, and these associations were partially mediated by MSs. Adherence to healthy dietary patterns may potentially reduce frailty development by modulating metabolites.

Dysregulation of acyl carnitines, pentose phosphate pathway and arginine and ornithine metabolism are associated with decline in intrinsic capacity in Chinese older adults.

BACKGROUND: Intrinsic capacity is the combination of individual physical and mental abilities, reflecting the aging degree of the older adults. However, the mechanisms and metabolic characteristics of the decline in intrinsic capacity are still unclear. AIMS: To identify metabolic signatures and associated pathways of decline in intrinsic capacity based on the metabolite features. METHODS: We recruited 70 participants aged 77.19 ± 8.31 years. The five domains of intrinsic capacity were assessed by Short Physical Performance Battery (for mobility), Montreal cognition assessment (for cognition), 30-Item Geriatric Depression Scale (for psychology), self-reported hearing/visual impairment (for sensory) and Nutritional risk screening (for vitality), respectively. The serum samples of participants were analyzed by liquid chromatography-mass spectrometry-based metabolomics, followed by metabolite set enrichment analysis and metabolic pathway analysis. RESULTS: There were 50 participants with a decline in intrinsic capacity in at least one of the domains. A total of 349 metabolites were identified from their serum samples. Overall, 24 differential metabolites, 5 metabolite sets and 13 pathways were associated with the decline in intrinsic capacity. DISCUSSION: Our results indicated that decline in intrinsic capacity had unique metabolomic profiles. CONCLUSION: The specific change of acyl carnitines was observed to be a feature of decline in intrinsic capacity. Dysregulation of the pentose phosphate pathway and of arginine and ornithine metabolism was strongly associated with the decline in intrinsic capacity.

Transition to healthier lifestyle associated with reduced risk of incident dementia and decreased hippocampal atrophy.

BACKGROUND: Research has estimated the associations of lifestyle at one-time point with the risk of dementia and hippocampal volume, but the impact of lifestyle transition on dementia and hippocampal volume remains unclear. This study aims to examine the associations of lifestyle transition with the risk of dementia and hippocampal volume. METHODS: Based on data from the UK Biobank, a weighted lifestyle score was constructed by incorporating six lifestyle factors. Within each baseline lifestyle group (i.e., healthy, intermediate, and unhealthy), lifestyle transition was classified into decline, maintenance, and improvement. Cox proportional hazard regression was used to estimate the association of lifestyle transition and incident dementia (N = 16,305). A multiple linear regression model was used to estimate the association between lifestyle transition and hippocampal volume (N = 5849). RESULTS: During a median follow-up period of 8.6 years, 120 (0.7 %) dementia events were documented. Among participants with healthy baseline lifestyles, the improvement group had a lower risk of incident dementia (HR: 0.18, 95 % CI: 0.04-0.81) and a larger hippocampal volume (ß = 111.69, P = 0.026) than the decline group. Similar results were observed among participants with intermediate baseline lifestyles regarding dementia risk but not hippocampal volume. No benefits were observed in the improvement group among those with unhealthy baseline lifestyles. LIMITATIONS: A lower incidence of dementia than other cohort study and this may have resulted in an underestimation of the risk of dementia. CONCLUSIONS: Earlier transitions to healthier lifestyle were associated with reduced risk of incident dementia and decreased hippocampal atrophy.

Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality.

BACKGROUND: With two well-validated aging measures capturing mortality and morbidity risk, this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes. METHODS: Data were from 405,944 adults (40-69 years) from UK Biobank (UKB) and 9972 adults (20-84 years) from the US National Health and Nutrition Examination Survey (NHANES). An unhealthy lifestyles score (range: 0-5) was constructed based on five factors (smoking, drinking, physical inactivity, unhealthy body mass index, and unhealthy diet). Two aging measures, Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel) were calculated using nine and seven blood biomarkers, respectively, with a higher value indicating the acceleration of aging. The outcomes included incident cardiovascular disease (CVD), incident cancer, and all-cause mortality in UKB; CVD mortality, cancer mortality, and all-cause mortality in NHANES. A general linear regression model, Cox proportional hazards model, and formal mediation analysis were performed. RESULTS: The unhealthy lifestyles score was positively associated with PhenoAgeAccel (UKB: ß = 0.741; NHANES: ß = 0.874, all p < 0.001). We further confirmed the respective associations of PhenoAgeAccel and unhealthy lifestyles with the outcomes in UKB and NHANES. The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident CVD, incident cancer, and all-cause mortality were 20.0%, 17.8%, and 26.6% (all p < 0.001) in UKB, respectively. Similar results were found in NHANES. The findings were robust when using another aging measure-BioAgeAccel. CONCLUSIONS: Accelerated aging partially mediated the associations of lifestyles with CVD, cancer, and mortality in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late life beyond lifestyle interventions.

Social Determinants of Intrinsic Capacity: A National Cohort Study.

INTRODUCTION: Intrinsic capacity (IC), a composite of physical and mental capacities, is a marker of healthy aging. Social determinants of health (SDOH), namely the economic and social environments across a lifespan, are the most fundamental factors influencing health outcomes and health disparities. However, there is limited evidence on the influence of the individual and combined burden of the SDOH on IC. METHODS: Data were obtained from the China Health and Retirement Longitudinal Study (2011-2015), and data analysis was conducted in 2023. Linear mixed-effect regression was employed to investigate the association between SDOH and IC in a longitudinal analysis. RESULTS: This study comprised 7,669 participants (mean [SD] age, 68.5 [7.1] years; 49.8% female; mean [SD] IC, 7.2 [1.6]). In the longitudinal analysis, all five SDOH domains were independently and significantly associated with IC. The absence of social association within the social and community context domain exhibited the weakest association with IC (ß: -0.11 [95% CI -0.20, -0.02]), while illiteracy within the education access and quality domain demonstrated the strongest association with IC (ß: -0.51 [95% CI -0.60, -0.42]). Furthermore, the adverse effects of SDOH on IC became more distinguishable with the cumulative number of SDOH variables (coefficient for 2 SDOH, -0.41 [-0.64, -0.19]; 3 SDOH, -0.70 [-0.93, -0.48]; ≥4 SDOH, -1.10 [-1.33, -0.88]) compared with those without any SDOH. CONCLUSIONS: Certain SDOH levels were significantly and negatively associated with IC. Targeted interventions may be needed to improve SDOH in individuals at high risk of poor IC.

Associations between dietary magnesium intake and hypertension, diabetes, and hyperlipidemia.

Hypertension, diabetes, and hyperlipidemia significantly impact chronic diseases and mortality. Magnesium is an essential nutrient for maintaining critical physiological functions, and magnesium deficiency is often associated with adverse health outcomes. In a cross-sectional study of US adults, we aimed to explore dietary magnesium intake and its association with the prevalence of hypertension, diabetes, and hyperlipidemia in US adults over 20 years of age in NHANES 2007-2018. We obtained data on 24,171 samples of hypertension, 9950 samples of diabetes, and 12,149 samples of hyperlipidemia. We used multivariable logistic regression models adjusted for multiple sociodemographic, anthropometric, and lifestyle factors, with participants subdivided into five groups based on quintiles of daily dietary magnesium. After adjusting for the major lifestyle and dietary variables, an independent and significant inverse relationship between dietary magnesium and hypertension, diabetes, and hyperlipidemia was observed. Compared with the lowest quintile of magnesium intake, the prevalence of hypertension, diabetes, and hyperlipidemia was significantly reduced in the highest magnesium quintile. The OR of hypertension in the highest quintile was 0.66 (95% CI: 0.51-0.87; P trend < 0.001), the OR of diabetes was 0.56 (95% CI: 0.39-0.81; P trend < 0.001), and the OR of hyperlipidemia was 0.68 (95% confidence interval: 0.53-0.86; P trend = 0.007). In the subgroup analysis, most of the inverse relationships persisted. Our findings highlight the potential of magnesium-rich foods to prevent hypertension, diabetes, and hyperlipidemia in US adults. This article summarizes and discuss recent findings on: 1) A high dietary magnesium intake was associated with a lower prevalence of hypertension; 2) An inverse relationship between dietary magnesium with diabetes hyperlipidemia; 3) Monitoring and management of magnesium was important.