Association of Childhood Adversity With Frailty and the Mediating Role of Unhealthy Lifestyle: A Lifespan Analysis.

OBJECTIVES: Childhood adversity and lifestyle have been associated with frailty in later life, but not much is known about factors that may explain these associations. Therefore, this study aims to investigate the association of childhood adversity with frailty, and the mediating role of unhealthy lifestyle in the association. METHODS: This lifespan analysis included 152,914 adults aged 40-69 years old from the UK Biobank. We measured childhood adversity with five items: physical neglect, emotional neglect, sexual abuse, physical abuse, and emotional abuse through online mental health survey. Frailty was measured by the frailty index; an unhealthy lifestyle score (range: 0-5) was calculated based on unhealthy body mass index, smoking, alcohol consumption, physical inactivity, and unhealthy diet at the baseline survey. Multiple logistic regression and mediation analysis were performed. RESULTS: A total of 10,078 participants (6.6%) were defined as having frailty. Participants with any childhood adversity had higher odds of frailty. For example, in the fully adjusted model, with a one-point increase in cumulative score of childhood adversity, the odds of frailty increased by 38% (odds ratio: 1.38; 95% Confidence Interval: 1.36, 1.40). Unhealthy lifestyle partially mediated the associations of childhood adversity with frailty (mediation proportion: 4.4%-7.0%). The mediation proportions were largest for physical (8.2%) and sexual (8.1%) abuse. CONCLUSIONS: Childhood adversity was positively associated with frailty, and unhealthy lifestyle partially mediated the association. This newly identified pathway highlights the potential of lifestyle intervention strategies among those who experienced childhood adversity (in particular, physical, and sexual abuse) to promote healthy aging.

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.

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.

Association of frailty with the incidence risk of cardiovascular disease and type 2 diabetes mellitus in long-term cancer survivors: a prospective cohort study.

BACKGROUND: Comorbidities among cancer survivors remain a serious healthcare burden and require appropriate management. Using two widely used frailty indicators, this study aimed to evaluate whether frailty was associated with the incidence risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) among long-term cancer survivors. METHODS: We included 13,388 long-term cancer survivors (diagnosed with cancer over 5 years before enrolment) free of CVD and 6101 long-term cancer survivors free of T2DM, at the time of recruitment (aged 40-69 years), from the UK Biobank. Frailty was assessed by the frailty phenotype (FP_Frailty, range: 0-5) and the frailty index (FI_Frailty, range: 0-1) at baseline. The incident CVD and T2DM were ascertained through linked hospital data and primary care data, respectively. The associations were examined using Cox proportional hazards regression models. RESULTS: Compared with non-frail participants, those with pre-frailty (FP_Frailty [met 1-2 of the components]: hazard ratio [HR]=1.18, 95% confidence interval [CI]: 1.05, 1.32; FI_Frailty [0.10< FI ≤0.21]: HR=1.51, 95% CI: 1.32, 1.74) and frailty (FP_Frailty [met ≥3 of the components]: HR=2.12, 95% CI: 1.73, 2.60; FI_Frailty [FI >0.21]: HR=2.19, 95% CI: 1.85, 2.59) had a significantly higher risk of CVD in the multivariable-adjusted model. A similar association of FI_Frailty with the risk of incident T2DM was observed. We failed to find such an association for FP_Frailty. Notably, the very early stage of frailty (1 for FP_Frailty and 0.1-0.2 for FI_Frailty) was also positively associated with the risk of CVD and T2DM (FI_Frailty only). A series of sensitivity analyses confirmed the robustness of the findings. CONCLUSIONS: Frailty, even in the very early stage, was positively associated with the incidence risk of CVD and T2DM among long-term cancer survivors, although discrepancies existed between frailty indicators. While the validation of these findings is required, they suggest that routine monitoring, prevention, and interventive programs of frailty among cancer survivors may help to prevent late comorbidities and, eventually, improve their quality of life. Especially, interventions are recommended to target those at an early stage of frailty when healthcare resources are limited.

Association of solid fuel use with a risk score capturing dementia risk among middle-aged and older adults: A prospective cohort study.

OBJECTIVES: Whether household air pollution is associated with dementia risk remains unknown. This study examined the associations between solid fuel use for cooking and heating (the main source of household air pollution) and dementia risk. METHODS: This analysis included data on 11,352 participants (aged 45+ years) from the 2011 wave of China Health and Retirement Longitudinal Study, with follow-up to 2018. Dementia risk was assessed by a risk score using the Rotterdam Study Basic Dementia Risk Model (BDRM), which was subsequently standardized for analysis. Household fuel types of cooking and heating were categorized as solid (e.g., coal and crop residue) and clean (e.g., central heating and solar). Multivariable analyses were performed using generalized estimating equations. Moreover, we examined the joint associations of solid fuel use for cooking and heating with the BDRM score. RESULTS: After adjusting for potential confounders, we found an independent and significant association of solid (vs. clean) fuel use for cooking and heating with a higher BDRM score (e.g., ß = 0.17 for solid fuel for cooking; 95% confidence interval [CI]: 0.15-0.19). Participants who used solid (vs. clean) fuel for both cooking and heating had the highest BDRM score (ß = 0.32; 95% CI: 0.29-0.36). Subgroup analysis suggested stronger associations in participants living in rural areas. CONCLUSIONS: Solid fuel use for cooking and heating was independently associated with increased dementia risk in Chinese middle-aged and older adults, particularly among those living in rural areas. Our findings call for more efforts to facilitate universal access to clean energy for dementia prevention.

Comparison of healthspan-related indicators between adults with and without HIV infection aged 18-59 in the United States: a secondary analysis of NAHNES 1999-March 2020.

BACKGROUND: As persons with HIV (PWH) live longer they may experience a heightened burden of poor health. However, few studies have characterized the multi-dimentional health of PWH. Thus, we aimed to identify the extent and pattern of health disparities, both within HIV infection status and across age (or sex) specific groups. METHODS: We used cross-sectional data from the US National Health and Nutrition Examination Survey, 1999-March 2020. The adjusted prevalence of six healthspan-related indicators-physical frailty, activities of daily living (ADL) disability, mobility disability, depression, multimorbidity, and all-cause death-was evaluated. Logistic regression and Cox proportional hazards analyses were used to investigate associations between HIV status and healthspan-related indicators, with adjustment for individual-level demographic characteristics and risk behaviors. RESULTS: The analytic sample consisted of 33 200 adults (170 (0.51%) were PWH) aged 18-59 years in the United States. The mean (interquartile range) age was 35.1 (25.0-44.0) years, and 49.4% were male. PWH had higher adjusted prevalences for all of the 6 healthspan-related indicators, as compared to those without HIV, ranged from 17.4% (95% CI: 17.4%, 17.5%) vs. 2.7% (95%CI: 2.7%, 2.7%) for all-cause mortality, to 84.3% (95% CI: 84.0%, 84.5%) vs. 69.8% (95%CI: 69.7%, 69.8%) for mobility disability. While the prevalence difference was largest in ADL disability (23.4% (95% CI: 23.2%, 23.7%); P < 0.001), and least in multimorbidity (6.9% (95% CI: 6.8%, 7.0%); P < 0.001). Generally, the differences in prevalence by HIV status were greater in 50-59 years group than those in 18-29 group. Males with HIV suffered higher prevalence of depression and multimorbidity, while females with HIV were more vulnerable to functional limitation and disabilities. HIV infection was associated with higher odds for 3 of the 6 healthspan-related indicators after fully adjusted, such as physical frailty and depression. Sensitivity analyses did not change the health differences between adults with and without HIV infection. CONCLUSIONS: In a large sample of U.S. community-dwelling adults, by identifying the extent and pattern of health disparities, we characterized the multi-dimentional health of PWHs, providing important public health implications for public policy that aims to improve health of persons with HIV and further reduce these disparities.

Cooking or heating with solid fuels increased the all-cause mortality risk among mid-aged and elderly People in China.

BACKGROUND: Our study aimed to explore the associations between solid fuels burning for either heating or cooking and all-cause mortality based on 2859 participants from the China Health and Retirement Longitudinal Study during 2011-2018. METHODS: Logistic regression models were performed to estimate the risk for all-cause mortality between different types of fuels in the current longitudinal study. Furthermore, the combined impacts of applying solid fuels for both cooking and heating and the effect among those who switched types of fuels in cooking or heating during follow-up were also analyzed. Interaction and stratification analysis by covariables was applied further to explore the relationship between fuel burning and all-cause mortality. RESULTS: After full-adjustment, usage of solid fuels was associated with higher all-cause mortality (for heating: OR = 1.93, 95% CI = 1.25, 3.00; for cooking: OR = 1.76, 95% CI = 1.10, 2.82). Using solid fuels for both cooking and heating (OR = 2.36; 95% CI, 1.38, 4.03) was associated with a higher risk of all-cause mortality, while using solid fuels with a single purpose was not (OR = 1.52; 95% CI, 0.90, 2.55). Protective tendencies were detected in switching solid to clean fuel for cooking (OR = 0.62; 95% CI, 0.32, 1.17) and heating (OR = 0.62; 95% CI, 0.35, 1.10). CONCLUSION: Either cooking or heating with solid fuels increases the risk of all-cause mortality among Chinese mid-aged and aging people in the urban area of China.

C-reactive protein and white blood cell are associated with frailty progression: a longitudinal study.

BACKGROUND: Systemic inflammation has been linked to diseases and frailty. However, little is known about the effect of systemic inflammation on frailty progression with a longitudinal study design. OBJECTIVES: This study aimed to investigate the associations of two inflammation indicators, C-reactive protein (CRP) and white blood cell (WBC), with frailty progression. METHODS: This study utilized data from the China Health and Retirement Longitudinal Study 2011-2018 (wave 1-wave 4). Frailty index (FI) was calculated using 40 items from wave 1 to wave 4 (range: 0 to 1). Two systemic inflammation biomarkers, CRP and WBC, were measured at baseline (wave 1) and logs transformed as continuous variables or grouped using quartiles. Linear mixed-effect models were used to analyze the associations of these two biomarkers with the progression of frailty with adjustment for potential confounding factors. RESULTS: The study enrolled 9111 middle-aged and older participants (52.7% females, mean age 58.8 ± 9.3 years). The median follow-up time was 7.0 years. In a fully adjusted model with further adjustment for baseline FI, higher CRP (ß for the interaction with time = 0.239, 95% CI: 0.139 to 0.338) and WBC (ß for the interaction with time = 0.425, 95% CI: 0.024 to 0.825) significantly accelerated the rate of increase in the FI during the follow-up period. The associations were more pronounced in younger people (< 60 years) than older people (≥60 years). CONCLUSIONS: Higher CRP and WBC accelerated the progression of frailty, particularly in younger groups (< 60 years). The findings suggest the importance of systemic inflammation for the early identification of people at high risk of rapid progression of frailty.

Association of immunity markers with the risk of incident frailty: the Rugao longitudinal aging study.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) are readily available circulatory immunity markers that are associated with components of frailty. However, few studies have investigated the relationship between these immunity markers and frailty, and it remains unknown whether they are predictive of incident frailty in older adults in general. Hence, we aimed to examine the association of these immunity markers with the risk of incident frailty. RESULTS: Overall, 1822 older adults (mean age was 78.03 ± 4.46 years) were included in the Rugao Longitudinal Aging Study. NLR, PLR and SII were calculated from blood cell counts. The frailty definition was based on the Fried phenotype. At baseline, 200 (10.98%) individuals were defined as frailty, and no significant associations of NLR, PLR and SII with frailty were found. During the 2-year follow-up, 180 (15.67%) individuals were new-onset frailty. After adjustment, an increased logNLR (odds ratio [OR] 2.92, 95% confidence interval [CI] 1.20-7.18), logPLR (OR 2.54, 95% CI: 1.01-6.53) and logSII (OR 2.34, 95% CI: 1.16-4.78) were significantly associated with a higher risk of incident frailty in all individuals. Additionally, the associations of logNLR (OR 4.21, 95% CI 1.54-11.62 logPLR (OR 3.38, 95% CI: 1.17-9.91) and logSII (OR 2.56, 95% CI: 1.15-5.72) with incident frailty were remained after excluding individuals with comorbidities. In further analyzed, individuals with higher levels of NLR and SII had higher risk of incident frailty when we stratified individuals by quartiles of these immunity markers. CONCLUSION: NLR and SII are easily obtained immunity markers that could be used to predict incident frailty in clinical practice.

Aging metrics incorporating cognitive and physical function capture mortality risk: results from two prospective cohort studies.

BACKGROUND: Aging metrics incorporating cognitive and physical function are not fully understood, hampering their utility in research and clinical practice. This study aimed to determine the proportions of vulnerable persons identified by three existing aging metrics that incorporate cognitive and physical function and the associations of the three metrics with mortality. METHODS: We considered three existing aging metrics including the combined presence of cognitive impairment and physical frailty (CI-PF), the frailty index (FI), and the motoric cognitive risk syndrome (MCR). We operationalized them using data from the China Health and Retirement Longitudinal Study (CHARLS) and the US National Health and Nutrition Examination Survey (NHANES). Logistic regression models or Cox proportional hazards regression models, and receiver operating characteristic curves were used to examine the associations of the three metrics with mortality. RESULTS: In CHARLS, the proportions of vulnerable persons identified by CI-PF, FI, and MCR were 2.2, 16.6, and 19.6%, respectively. Each metric predicted mortality after adjustment for age and sex, with some variations in the strength of the associations (CI-PF, odds ratio (OR) (95% confidence interval (CI)) 2.87 (1.74-4.74); FI, OR (95% CI) 1.94 (1.50-2.50); MCR, OR (95% CI) 1.27 (1.00-1.62)). CI-PF and FI had additional predictive utility beyond age and sex, as demonstrated by integrated discrimination improvement and continuous net reclassification improvement (all P < 0.001). These results were replicated in NHANES. CONCLUSIONS: Despite the inherent differences in the aging metrics incorporating cognitive and physical function, they consistently capture mortality risk. The findings support the incorporation of cognitive and physical function for risk stratification in both Chinese and US persons, but call for caution when applying them in specific study settings.

Catastrophic health expenditure among Chinese adults living alone with cognitive impairment: findings from the CHARLS.

BACKGROUND: The catastrophic health expenditure of older adults results in serious consequences; however, the issue of whether cognitive status and living situations contribute to such financial burdens is uncertain. Our aim was to compare the differences in catastrophic health expenditure between adults living alone with cognitive impairment and those adults living with others and with normal cognition. METHODS: We identified 909 observations of participants living alone with cognitive impairment (cases) and 37,432 observations of participants living with others and with normal cognition (comparators) from the 2011/2012, 2013, 2015 and 2018 waves of the China Health and Retirement Longitudinal Study (CHARLS). We used propensity score matching (1:2) to create matched cases and comparators in a covariate-adjusted logistic regression analysis. Catastrophic health expenditure was defined as an out-of-pocket cost for health care ≥40% of a household's capacity to pay. RESULTS: In comparison with participants living with others and with normal cognition, those adults living alone with cognitive impairment reported a higher percentage of catastrophic health expenditure (19.5% vs. 11.8%, respectively, P < 0.001). When controlling for age, sex, education, marital status, residence areas, alcohol consumption, smoking status and disease counts, we found that this subpopulation had significantly higher odds of having catastrophic health expenditure (odds ratio [OR] = 1.89, 95% confidence interval [CI]: 1.40, 2.56). Additional analyses confirmed the robustness of the results. CONCLUSIONS: This study demonstrated that adults living alone with cognitive impairment in the CHARLS experienced a high burden of catastrophic health expenditure. Health care policies on social health insurance and medical assistance should consider these vulnerable adults.

Does healthy lifestyle attenuate the detrimental effects of urinary polycyclic aromatic hydrocarbons on phenotypic aging? An analysis from NHANES 2001-2010.

Existing evidence has showed that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of many chronic diseases. Given the close connection between aging (a major risk factor) and chronic diseases, however, very few studies have evaluated the association between PAHs and aging. Furthermore, whether modifiable healthy lifestyle could attenuate the detrimental effect of PAHs on aging remains unknown. Therefore, we conducted this study, aiming to: (1) examine the associations of urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) and lifestyle with Phenotypic Age Acceleration (PhenoAge.Accel), a novel aging measure that captures morbidity and mortality risk; and (2) evaluate the potential interaction effects of OH-PAHs and lifestyle on PhenoAge.Accel. Cross-sectional data of 2,579 participants (aged 20-84 years, n = 1,292 females) from the National Health and Nutrition Examination Survey for years 2001-2010 were analyzed. A lifestyle index was constructed based on five components (drinking, smoking, body mass index, physical activity, and diet), ranging from 0 to 5. We calculated PhenoAge.Accel using algorithms developed previously. General linear regression models were used to examine the associations. We observed strong associations of OH-PAHs and lifestyle with PhenoAge.Accel. For instance, one unit increase in ∑NAP (sum of 1- and 2-hydroxynaphthalene) was associated with 0.37 year (95% confidence interval [CI]: 0.26, 0.48) increase in PhenoAge.Accel. We did not observe statistically significant interaction effects between OH-PAHs and lifestyle on PhenoAge.Accel. After stratified by sex, we observed strong associations as well as statistically significant interactions of OH-PAHs and lifestyle with PhenoAge.Accel among females. In conclusion, both OH-PAHs and lifestyle were independently associated with phenotypic aging and there were statistically significant interactions between OH-PAHs and lifestyle on phenotypic aging among females. The findings highlight the importance of adherence to a healthy lifestyle to attenuate the detrimental effects of exposures to PAHs on phenotypic aging among females.

Association of blood mercury exposure with depressive symptoms in the Chinese oldest old.

Depressive symptoms have a significant impact on the quality-of-life among the oldest old (aged ≥ 80 years) in the population. Current research on the association of blood mercury with depressive symptoms has mainly targeted the general population. However, it is unclear whether this association is present in the oldest old. We used data from the Healthy Aging and Biomarker Cohort Study carried out in 2017-2018, with 1154 participants aged ≥ 80 years eligible for analysis. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to detect blood mercury (Hg) levels, while the CES-D10 depression scale was used to assess depressive symptoms. The association between blood mercury levels and depressive symptoms was investigated using log-binomial and Poisson regression models. We also used restricted cubic splines (RCS) to assess the linear or nonlinear association of blood mercury with depressive symptoms scores. The 1154 participants ranged in age from 80 to 120 years, while the geometric mean of blood mercury concentration was 1.01 µg/L. After adjustment for covariates, log-binomial and Poisson regression analyses revealed a statistically significant, positive association of blood mercury with depressive symptoms. In comparison to the first tertile, the adjusted relative risks of blood mercury and the presence of depressive symptoms in the second and third tertiles were 1.55 (1.20-1.99) and 1.45 (1.11-1.90), respectively. The RCS model showed a linear association between blood mercury level and depressive symptoms scores. In conclusion, among the oldest old, we demonstrated that blood mercury levels were positively associated with depressive symptoms. Further surveys, especially cohort studies and clinical trials are needed to confirm these results.

Modeling of correlated cognitive function and functional disability outcomes with bounded and missing data in a longitudinal aging study.

Longitudinal studies of correlated cognitive and disability outcomes among older adults are characterized by missing data due to death or loss to follow-up from deteriorating health conditions. The Mini-Mental State Examination (MMSE) score for assessing cognitive function ranges from a minimum of 0 (floor) to a maximum of 30 (ceiling). To study the risk factors of cognitive function and functional disability, we propose a shared parameter model to handle missingness, correlation between outcomes, and the floor and ceiling effects of the MMSE measurements. The shared random effects in the proposed model handle missingness (either missing at random or missing not at random) and correlation between these outcomes, while the Tobit distribution handles the floor and ceiling effects of the MMSE measurements. We used data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) and a simulation study. By ignoring the MMSE floor and ceiling effects in the analyses of the CLHLS, the association of systolic blood pressure with cognitive function was not significant and the association of age with cognitive function was lower by 16.6% (from -6.237 to -5.201). By ignoring the MMSE floor and ceiling effects in the simulation study, the relative bias in the estimated association of female gender with cognitive function was 43 times higher (from -0.01 to -0.44). The estimated associations obtained with data missing at random were smaller than those with data missing not at random, demonstrating how the missing data mechanism affects the analytic results. Our work underscores the importance of proper model specification in longitudinal analysis of correlated outcomes subject to missingness and bounded values.

Association between elder abuse and telomere shortening in older adults: A 2-year prospective study.

BACKGROUNDS: Elder abuse is a public health issue associated with increased morbidity and mortality. Its impact on victims' health at the cellular level, however, remains unknown. This study assessed the association between abuse exposure and shortening of telomere length (TL), a promising molecular marker for biological aging, in older victims. SETTING: The geriatric departments of three Grade-A hospitals in the People's Republic of China (PRC). PARTICIPANTS: Six hundred Chinese older adults, including 300 abused victims and 300 non-abused controls were randomly drawn respectively from a larger sample of 467 abused and 518 non-abused older adults recruited at baseline. Participants were assessed for physical and psychological abuse exposure at baseline between September 2015 and February 2016 and assessed for TL 2 years after the abuse assessment. MEASUREMENTS: TL was quantified using a quantitative PCR method and expressed as T/S ratio (the ratio of telomere repeat copy numbers to single-copy gene numbers). Physical and psychological abuse was measured using the Revised Conflicts Tactics Scale. RESULTS: Adjusting for demographic, medical, and behavioral confounders, physical and psychological abuse exposure at baseline were independently associated with shorter TL at follow-up. The association was the most significant between multiple forms of abuse (physical and psychological) exposure and shorter TL. CONCLUSION: This study provides the first evidence on the relationship between abuse and shortened TL in older victims, implying the potential effect of elder abuse on accelerated cellular aging. The findings suggest the importance of routinely assessing and intervening abuse in older adults by healthcare professionals, to promote and maintain physical health in older adults.

Burden of caregivers who care for oldest-old parents with disability: A cross-sectional study.

OBJECTIVE: To describe the characteristics of oldest-old Chinese with disability and their adult-child caregivers, and the extent to which these characteristics were associated with caregiver burden. METHODS: The study was based on 168 pairs of disabled oldest-old adults and their adult-child caregivers, derived from the Chinese Longitudinal Healthy Longevity Survey. Descriptive analyses of care recipients' and caregivers' characteristics were conducted respectively, in reference to caregiver burden. Statistically significant characteristics identified in these bivariate analyses were then jointly evaluated in multiple linear regression models with caregiver burden as the outcome. RESULTS: Care recipients positive emotion status [(ß = -0.227 (-0.412, -0.042)], multiple chronic disease [(ß = 0.513 (0.081, 0.945)], and caregivers spent more caregiving time [(ß = 0.225 (0.061, 0.389)] were main factors associated with caregiver burden. CONCLUSION: Adult-children caregivers perceived heavier burden if care recipients had low positive emotions, had multiple chronic diseases, and caregivers spent more time caregiving.

Population ageing and mortality during 1990-2017: A global decomposition analysis.

BACKGROUND: As the number of older people globally increases, health systems need to be reformed to meet the growing need for medical resources. A few previous studies reported varying health impacts of population ageing, but they focused only on limited countries and diseases. We comprehensively quantify the impact of population ageing on mortality for 195 countries/territories and 169 causes of death. METHODS AND FINDINGS: Using data from the Global Burden of Disease Study 2017 (GBD 2017), this study derived the total number of deaths and population size for each year from 1990 to 2017. A decomposition method was used to attribute changes in total deaths to population growth, population ageing, and mortality change between 1990 and each subsequent year from 1991 through 2017, for 195 countries/territories and for countries grouped by World Bank economic development level. For countries with increases in deaths related to population ageing, we calculated the ratio of deaths attributed to mortality change to those attributed to population ageing. The proportion of people aged 65 years and older increased globally from 6.1% to 8.8%, and the number of global deaths increased by 9 million, between 1990 and 2017. Compared to 1990, 12 million additional global deaths in 2017 were associated with population ageing, corresponding to 27.9% of total global deaths. Population ageing was associated with increases in deaths in high-, upper-middle-, and lower-middle-income countries but not in low-income countries. The proportions of deaths attributed to population ageing in 195 countries/territories ranged from -43.9% to 117.4% for males and -30.1% to 153.5% for females. The 2 largest contributions of population ageing to disease-specific deaths globally between 1990 and 2017 were for ischemic heart disease (3.2 million) and stroke (2.2 million). Population ageing was related to increases in deaths in 152 countries for males and 159 countries for females, and decreases in deaths in 43 countries for males and 36 countries for females, between 1990 and 2017. The decreases in deaths attributed to mortality change from 1990 to 2017 were more than the increases in deaths related to population ageing for the whole world, as well as in 55.3% (84/152) of countries for males and 47.8% (76/159) of countries for females where population ageing was associated with increased death burden. As the GBD 2017 does not provide variances in the estimated death numbers, we were not able to quantify uncertainty in our attribution estimates. CONCLUSIONS: In this study, we found that population ageing was associated with substantial changes in numbers of deaths between 1990 and 2017, but the attributed proportion of deaths varied widely across country income levels, countries, and causes of death. Specific preventive and therapeutic techniques should be implemented in different countries and territories to address the growing health needs related to population ageing, especially targeting the diseases associated with the largest increase in number of deaths in the elderly.

Correction: A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.1002718.].

Associations of genetics, behaviors, and life course circumstances with a novel aging and healthspan measure: Evidence from the Health and Retirement Study.

BACKGROUND: An individual's rate of aging directly influences his/her susceptibility to morbidity and mortality. Thus, quantifying aging and disentangling how various factors coalesce to produce between-person differences in the rate of aging, have important implications for potential interventions. We recently developed and validated a novel multi-system-based aging measure, Phenotypic Age (PhenoAge), which has been shown to capture mortality and morbidity risk in the full US population and diverse subpopulations. The aim of this study was to evaluate associations between PhenoAge and a comprehensive set of factors, including genetic scores, childhood and adulthood circumstances, and health behaviors, to determine the relative contributions of these factors to variance in this aging measure. METHODS AND FINDINGS: Based on data from 2,339 adults (aged 51+ years, mean age 69.4 years, 56% female, and 93.9% non-Hispanic white) from the US Health and Retirement Study, we calculated PhenoAge and evaluated the multivariable associations for a comprehensive set of factors using 2 innovative approaches-Shapley value decomposition (the Shapley approach hereafter) and hierarchical clustering. The Shapley approach revealed that together all 11 study domains (4 childhood and adulthood circumstances domains, 5 polygenic score [PGS] domains, and 1 behavior domain, and 1 demographic domain) accounted for 29.2% (bootstrap standard error = 0.003) of variance in PhenoAge after adjustment for chronological age. Behaviors exhibited the greatest contribution to PhenoAge (9.2%), closely followed by adulthood adversity, which was suggested to contribute 9.0% of the variance in PhenoAge. Collectively, the PGSs contributed 3.8% of the variance in PhenoAge (after accounting for chronological age). Next, using hierarchical clustering, we identified 6 distinct subpopulations based on the 4 childhood and adulthood circumstances domains. Two of these subpopulations stood out as disadvantaged, exhibiting significantly higher PhenoAges on average. Finally, we observed a significant gene-by-environment interaction between a previously validated PGS for coronary artery disease and the seemingly most disadvantaged subpopulation, suggesting a multiplicative effect of adverse life course circumstances coupled with genetic risk on phenotypic aging. The main limitations of this study were the retrospective nature of self-reported circumstances, leading to possible recall biases, and the unrepresentative racial/ethnic makeup of the population. CONCLUSIONS: In a sample of US older adults, genetic, behavioral, and socioenvironmental circumstances during childhood and adulthood account for about 30% of differences in phenotypic aging. Our results also suggest that the detrimental effects of disadvantaged life course circumstances for health and aging may be further exacerbated among persons with genetic predisposition to coronary artery disease. Finally, our finding that behaviors had the largest contribution to PhenoAge highlights a potential policy target. Nevertheless, further validation of these findings and identification of causal links are greatly needed.

Are China's oldest-old living longer with less disability? A longitudinal modeling analysis of birth cohorts born 10 years apart.

BACKGROUND: China has transitioned from being one of the fastest-growing populations to among the most rapidly aging countries worldwide. In particular, the population of oldest-old individuals, those aged 80+, is projected to quadruple by 2050. The oldest-old represent a uniquely important group-they have high demand for personal assistance and the highest healthcare costs of any age group. Understanding trends in disability and longevity among the oldest-old-that is, whether successive generations are living longer and with less disability-is of great importance for policy and planning purposes. METHODS: We utilized data from successive birth cohorts (n = 20,520) of the Chinese oldest-old born 10 years apart (the earlier cohort was interviewed in 1998 and the later cohort in 2008). Disability was defined as needing personal assistance in performing one or more of five essential activities (bathing, transferring, dressing, eating, and toileting) or being incontinent. Participants were followed for age-specific disability transitions and mortality (in 2000 and 2002 for the earlier cohort and 2011 and 2014 for the later cohort), which were then used to generate microsimulation-based multistate life tables to estimate partial life expectancy (LE) and disability-free LE (DFLE), stratified by sex and age groups (octogenarians, nonagenarians, and centenarians). We additionally explored sociodemographic heterogeneity in LE and DFLE by urban/rural residence and educational attainment. RESULTS: More recently born Chinese octogenarians (born 1919-1928) had a longer partial LE between ages 80 and 89 than octogenarians born 1909-1918, and octogenarian women experienced an increase in partial DFLE of 0.32 years (P = 0.004) across the two birth cohorts. Although no increases in partial LE were observed among nonagenarians or centenarians, partial DFLE increased across birth cohorts, with a gain of 0.41 years (P < 0.001) among nonagenarians and 0.07 years (P = 0.050) among centenarians. Subgroup analyses revealed that gains in partial LE and DFLE primarily occurred among the urban resident population. CONCLUSIONS: Successive generations of China's oldest-old are living with less disability as a whole, and LE is expanding among octogenarians. However, we found a widening urban-rural disparity in longevity and disability, highlighting the need to improve policies to alleviate health inequality throughout the population.