G004, a synthetic sulfonylurea compound, exerts anti-atherosclerosis effects by targeting SIRT1 in ApoE-/- mice.

Atherosclerosis attracts increasing global attention because of its morbidity and mortality. G004, as a synthetic sulfonylurea compound, has been confirmed to have anti-hyperglycaemia, anti-platelet and anti-thrombus effects. The aim of the present study was to investigate whether G004 suppress the onset and development of atherosclerosis and illuminate its probable mechanism of action. ApoE-/- mice that were fed a high-fat diet were randomly divided into five groups by weight; subsequently, they were treated with vehicle, G004, at different doses or atorvastatin once daily for 12weeks. Meanwhile, C57BL/6 mice with the same diet served as the normal controls. Then, the serum lipid profiles and histopathological damage to the liver, kidney, aortic arch and aortic root were analysed. The activation of endothelial nitric oxide synthase (eNOS) and levels of inflammatory markers were detected. Reverse cholesterol transport (RCT) was assessed in vivo by intraperitoneal injection of RAW264.7 cells that were radiolabelled with 3H-cholesterol. The results indicated that G004 ameliorated the serum lipid accumulation, atherosclerotic lesions and liver steatosis. Additionally, this compound increased the expression of SIRT1 and eNOS as well as the phosphorylation and deacetylation of eNOS in the aorta, alleviating the inflammatory state. RCT was promoted in ApoE-/- mice, which was accompanied by increased expression of SIRT1/LXRα/ABCA1/G1 in the liver, and similar results appeared in the cholesterol efflux assay in RAW264.7 cells. The results provide a strong rationale for G004 to be an efficient anti-atherosclerosis agent that improved vascular endothelial dysfunction by stimulating SIRT1/eNOS and promoted RCT by stimulating SIRT1/LXRα/ABCA1/G1.

Cohort Profile: The Social Environment and Biomarkers of Aging Study (SEBAS) in Taiwan.

The Social Environment and Biomarkers of Aging Study (SEBAS) is a nationally representative longitudinal survey of Taiwanese middle-aged and older adults. It adds the collection of biomarkers and performance assessments to the Taiwan Longitudinal Study of Aging (TLSA), a nationally representative study of adults aged 60 and over, including the institutionalized population. The TLSA began in 1989, with follow-ups approximately every 3 years; younger refresher cohorts were added in 1996 and 2003. The first wave of SEBAS, based on a sub-sample of respondents from the 1999 TLSA, was conducted in 2000. A total of 1023 respondents completed both a face-to-face home interview and, several weeks later, a hospital-based physical examination. In addition to a 12-h (7 pm-7 am) urine specimen collected the night before and a fasting blood specimen collected during the examination, trained staff measured blood pressure, height, weight and waist and hip circumferences. A second wave of SEBAS was conducted in 2006 using a similar protocol to SEBAS 2000, but with the addition of performance assessments conducted by the interviewers at the end of the home interview. Both waves of SEBAS also included measures of health status (physical, emotional, cognitive), health behaviours, social relationships and exposure to stressors. The SEBAS data, which are publicly available at [http://www.icpsr.umich.edu/icpsrweb/NACDA/studies/3792/version/5], allow researchers to explore the relationships among life challenges, the social environment and health and to examine the antecedents, correlates and consequences of change in biological measures and health.

Change in depressive status and mortality in elderly persons: results of a national longitudinal study.

The authors aimed to investigate whether a change in depressive status was associated with a change in the risk of mortality in the elderly during a four-year follow-up period. Data came from the Survey of Health and Living Status of the Elderly in Taiwan. A cohort of 1784 men and women in Taiwan aged 65 or older who were assessed on two occasions in 1999 and 2003, and subsequently followed up until 2007. Depressive symptoms were assessed by the 10-item Center for Epidemiologic Studies Depression Scale (CES-D). The mortality risk of different depressive statuses was computed after adjustment for a variety of covariates. The data were further analyzed by gender and cause of death. Overall, chronic depression was associated with all-cause mortality (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.18-2.32) after 4 years of follow-up and controlling for covariates. When analyzing by gender, incident depression was associated with mortality in males only (HR=1.54; 95% CI=1.04-2.27). In females, only chronic depression was associated with a higher risk of mortality (HR=1.77; 95% CI=1.08-2.88). The increased risk of mortality with incident depression in males and chronic depression in females was attributed to non-cardiovascular disease (non-CVD) causes more than to CVD causes. In males, chronic depression predicted a higher incidence of CVD deaths. While chronic depression confers a greater risk of mortality in older women, incident depression predicts increased mortality in older men. The link between changing depressive status, gender, ethnicity and mortality warrants further investigation.

Depressive symptoms as an independent risk factor for mortality in elderly persons: results of a national longitudinal study.

OBJECTIVE: Depressive symptoms have been associated with increased mortality risk in previous cohort studies, but there is a paucity of research on Asian elderly in recent years. The authors investigated the depression-mortality link using data from a representative national cohort. METHODS: Data came from the Survey of Health and Living Status of the Elderly in Taiwan. A cohort of 2416 men and women in Taiwan aged 65 or older were followed up for eight years from 1999 to 2007. Depressive symptoms were assessed by the 10-item Center for Epidemiologic Studies Depression Scale. The mortality risk of depression was computed after adjustment for a variety of covariates. Data on the presence or absence of chronic diseases were further analyzed. RESULTS: Overall, depressive symptoms were associated with all-cause mortality (hazard ratio (HR), 1.21; 95% confidence interval (CI), 1.03-1.42) after eight years follow-up, but this mortality risk was detected in men only (HR, 1.27; 95% CI, 1.03-1.56), not in women (HR, 1.1; 95% CI, 0.86-1.4). Further analyses showed that in the group without chronic diseases (without diabetes mellitus, stroke, lung disease, cancer, or cognitive impairment), depressive symptoms were associated with mortality (HR, 1.40; 95% CI, 1.12-1.76) after eight years follow-up; however, there was no association between depressive symptoms and mortality in participants with chronic diseases (HR, 1.02; 95% CI, 0.82-1.26). CONCLUSION: Depressive symptoms are an independent risk factor for mortality in the elderly. Elderly depressive men and elderly without chronic diseases seemed to have a greater mortality risk.

Religious activity, life expectancy, and disability-free life expectancy in Taiwan.

Research has implicated religious activity as a health determinant, but questions remain, including whether associations persist in places where Judeo-Christian religions are not the majority; whether public versus private religious expressions have equivalent impacts, and the precise advantage expressed as years of life. This article addresses these issues in Taiwan. 3,739 Taiwanese aged 53+ were surveyed in 1999, 2003, and 2007. Mortality and disability were recorded. Religious activities in public and private settings were measured at baseline. Multistate life-tables produced estimates of total life expectancy and activity of daily living (ADL) disability-free life expectancy across levels of public and private religious activity. There is a consistent positive gradient between religious activity and expectancy with greater activity related to longer life and more years without disability. Life and ADL disability-free life expectancies for those with no religious affiliation fit in between the lowest and highest religious activity groups. Results corroborate evidence in the West. Mechanisms that intervene may be similar in Eastern religions despite differences in the ways in which popular religions are practiced. Results for those with no affiliation suggest benefits of religion can be accrued in alternate ways.

Social support and mobility limitation as modifiable predictors of improvement in depressive symptoms in the elderly: results of a national longitudinal study.

Few national longitudinal studies have investigated the predictors of a better depression outcome in geriatric depression. This study examined the predictors of improvement in case-level depressive symptoms in the elderly. In this prospective cohort and population-based study in Taiwan, 206 non-demented and case-level depressed subjects aged 65 and older were interviewed at baseline in 2003 and follow-up in 2007. The independent variables included demographics, chronic medical diseases, and health-related behaviors assessed at baseline. The dependent variable was depressive symptoms, assessed using the 10-item short form of the Center for Epidemiologic Studies Depression Scale (CESD-10) assessed at follow-up. Multivariate analyses were used to identify the predictors of improvement in depression. The independent predictors of improvement in depression over a 4-year follow-up period are more social support and fewer mobility limitations at baseline. With regards to practical health-related behaviors, the 2 items of social support most associated with improvement in depression were willingness of significant others to talk with you and satisfaction with dependence upon significant others; the 2 items of mobility limitations most associated with non-improvement of depression were difficulty in carrying things and squatting. These findings suggested that health-related behaviors were important to the depression outcome in the elderly; moreover, interventions to improve depression should include practical health-related behaviors aimed at these modifiable risk factors.

Hierarchy of higher-level physical functions: a longitudinal investigation on a nationally representative population of community-dwelling middle-aged and elderly persons.

PURPOSE: Understanding the hierarchy of higher-level physical functions to infer disability level (mild, moderate or severe) is essential for the precise targeting of preventive interventions and has been examined previously in a cross-sectional study. Based on longitudinal data, this study evaluated the hierarchy of higher-level physical functions. METHODS: Data from a cohort of 2729 community-dwelling persons aged over 50 with no initial disability were drawn from the "Survey of Health and Living Status of the Elderly in Taiwan" from 1996 through 2007. The three-level hierarchy of eight chosen activities was examined by the median ages to disability onset with survival analyses and by Cox regressions, which examined the effects of sex and age on the development of this hierarchy. RESULTS: The progression of incident disability was as follows: mild level-running, carrying weight, and squatting; moderate level-climbing stairs, walking, and standing; and severe level-grasping and raising arms up. Women and older persons were at greater risk of developing more severe levels of disability. Another Cox regression with one index activity from each hierarchical level revealed similar results. CONCLUSIONS: The three-level hierarchy of higher-level physical functions has been validated longitudinally, suggesting rich research and clinical implications.

Leisure activity, mobility limitation and stress as modifiable risk factors for depressive symptoms in the elderly: results of a national longitudinal study.

Few national longitudinal studies have investigated the modifiable risk factors for depression in the elderly. This study investigated the risk factors and health-related behaviors associated with depressive symptoms using a national survey of Taiwanese elderly with a 4-year follow-up period. In this prospective cohort study, 1481 non-demented population-based elderly were interviewed at baseline in 2003 and at follow-up in 2007. The independent variables included demographics, chronic medical diseases and health-related behaviors assessed at baseline. The dependent variable was depressive symptoms assessed at follow-up. Reduced rank regression was applied to characterize independent factors related to depressive symptoms. The prevalence of depressive symptoms at follow-up was 21.1%. The results of multivariate analyses revealed three independent risk factors for depressive symptoms: fewer leisure activities (odds ratio, OR=0.56, 95% confidence interval, CI=0.38-0.83, p=0.0034), more mobility limitations (OR=1.93, 95% CI=1.30-2.86, p=0.0011) and higher stress levels (OR=2.43, 95% CI=1.68-3.50, p<0.0001). The leisure activities least associated with depression were reading newspapers/books and doing outdoor building projects; the two mobility limitations most associated with depression were difficulty in lifting things and in climbing stairs. The two stresses most associated with depression were perceived health stress and financial stress. These results indicated that interventions to prevent or reduce depression in older adults should include practical strategies aimed at these modifiable risk factors.

Healthy behaviors and onset of functional disability in older adults: results of a national longitudinal study.

OBJECTIVES: To examine the combined effect of healthy behaviors on the development of functional disability in an elderly cohort. DESIGN: Prospective cohort study. SETTING: Taiwan Longitudinal Study in Aging from 1989, 1993, 1996, 1999, and 2003. PARTICIPANTS: A national sample of 1,940 men and 1,247 women aged 60 and older without functional disability at baseline. MEASUREMENTS: Functional disability was defined as difficulty with activities of daily living: taking a bath or walking 200 to 300 m. Time to functional disability was the age at midpoint between the first occurrence of disability onset in the survey year and prior survey year. Considering that the onset of disability is probably a precursor of death, for those who died without disability, time to disability onset was set at the midpoint between the last follow-up and death year. Four healthy behaviors were measured: not smoking, moderate alcohol consumption, regular exercise, and sleeping 6 to 8 hours per day. A Cox proportional hazards model with time-dependent covariates was used to analyze the association between age at the first functional disability and prior healthy behavior, after controlling for sex, time-varying disease status, marital status, and education. RESULTS: Healthy behaviors were linked to the onset of functional disability. Participants who performed one or more healthy behaviors were 15% to 75% less likely to be disabled than those who performed none. CONCLUSION: In the population studied, healthy behaviors were associated with lower incidence of functional disability. As the number of healthy behaviors increased, the likelihood of disability decreased.

The pregnancy health and birth outcomes of women who underwent assisted reproductive technology: Results of a national survey.

BACKGROUND: There is an upward trend for parents to resort to assisted reproductive technology (ART) treatment due to delayed childbirth or birth difficulties. OBJECTIVE: This study investigates the pregnancy health and birth outcomes of women who underwent ART and analyzes the factors that influence birth weight to become<10 percentile when undergoing ART. MATERIALS AND METHODS: This study analyzed results of the first wave of the Taiwan Birth Cohort study. Through stratified systematic sampling, 24,200 mother-and-child sampling pairs were obtained from a total of 206,741 live births in Taiwan in 2005; 366 of the babies were born with the use of ART. RESULTS: During pregnancy, mothers who used ART suffered from higher risks of complication than the natural conception counterparts, including gestational diabetes mellitus (GDM), pregnancy induced hypertension (PIH), and placenta previa. Additionally, babies born through ART had poorer outcomes than the natural conception groups: the low birth weight (<2500g) was 33.1% compared to 6.4% for babies born naturally. CONCLUSION: Pregnancy health and birth outcomes of women who underwent ART were worse than those who got natural conception. Types of maternal complication among ART women included GDM, PIH, and placenta previa. Having multiple births was the most important factor that causes low birth weight in babies. The results of this study can be used as a reference for the health and care of mothers and babies who use ART.

Determinants of cognitive impairment over time among the elderly in Taiwan: results of the national longitudinal study.

This study aimed to identify the risk factors for cognitive impairment among the elderly population in Taiwan. Data were drawn from three waves of the "Survey of Health and Living Status of the Elderly in Taiwan", a national longitudinal study started in 1989. We included respondents without dementia or cognitive impairment at baseline in 1993 and followed them over a 10-year period. Cognitive function was measured by the nine-item Short Portable Mental Status Questionnaire in 1993, 1999, and 2003. Independent variables, including age, sex, marital status, education, ethnicity, ADLs, IADLs, physical function, social participation, chronic diseases, smoking, and alcohol drinking, were collected at baseline in 1993. Depressive symptoms were assessed by the 10-item Center for Epidemiologic Studies Depression Scale (CES-D). Logistic regression was used to evaluate the predictive factors for cognitive impairment. Of the eligible 1,626 respondents, 72 (4.43%) and 484 (29.77%) individuals did not complete follow-up in 1999 and 2003, respectively, mostly due to death. Our results showed that older age (OR = 2.60, 95% CI = 1.79-3.78), being female, lower educational level, IADL disability (OR = 2.06, 95% CI = 1.38-3.09), and having a history of diabetes (OR = 1.70, 95% CI = 1.06-2.74) or stroke (OR = 2.36, 95% CI = 1.06-5.26) were independent predictors for cognitive impairment in Taiwan.

Areca nut chewing and mortality in an elderly cohort study.

Compared with the well-documented association with betel-related cancer, little is known about the long-term effect of areca nut chewing on other fatal diseases. The authors' analyses were based on a population-based cohort study in Taiwan, including 4,049 participants aged 60 years or older enrolled in 1989 and 2,462 participants aged 50-66 years enrolled in 1996. Information regarding betel quid chewing and covariates was collected at baseline and was updated at subsequent interviews. Proportional hazards analysis was performed to determine the effect of chewing on all-cause and cause-specific deaths. During a mean follow-up of 9.5 years, 2,309 deaths occurred. Ever chewers were at higher risk of only total (hazard ratio = 1.19, 95% confidence interval: 1.05, 1.35) and cerebrovascular (hazard ratio = 1.66, 95% confidence interval: 1.19, 2.30) deaths. Furthermore, increased chewing-years or quid-years appeared to be associated with increased mortality risk (linear trend: p = 0.02 for total mortality and p = 0.001 for cerebrovascular mortality). The authors found that, although betel quid chewing resulted in a statistically significant increase in the risk of total and cerebrovascular deaths in the elderly population, the associations were weak and should be interpreted with caution. Further studies are needed to confirm these findings and to better understand the possible mechanisms of death.

The effects of Taiwan's National Health Insurance on access and health status of the elderly.

The primary objective of this paper is to evaluate the impact of Taiwan's National Health Insurance program (NHI), established in 1995, on improving elderly access to care and health status. Further, we estimate the extent to which NHI reduces gaps in access and health across income groups. Using data from a longitudinal survey, we adopt a difference-in-difference methodology to estimate the causal effect of Taiwan's NHI. Our results show that Taiwan's NHI has significantly increased utilization of both outpatient and inpatient care among the elderly, and such effects were more salient for people in the low- or middle-income groups. Our findings also reveal that although Taiwan's NHI greatly increased the utilization of both outpatient and inpatient services, this increased utilization of health services did not reduce mortality or lead to better self-perceived general health status for Taiwanese elderly. Measures more sensitive than mortality and self-perceived general health may be necessary for discerning the health effects of NHI. Alternatively, the lack of NHI effects on health may reflect other quality and efficiency problems inherent in the system not yet addressed by NHI.

Religious involvement and health outcomes among older persons in Taiwan.

We use data from a nationally representative, longitudinal survey of older Taiwanese to examine the relationship between religious involvement-including religious affiliation, religious attendance, beliefs, and religious practices-and self-reported measures of overall health status, mobility limitations, depressive symptoms, and cognitive function; clinical measures of systolic and diastolic blood pressure, serum interleukin-6, and 12-h urinary cortisol; and 4-year mortality. Frequency of religious attendance shows the strongest, most consistent association with health outcomes. But, with only one exception, this relationship disappears in the presence of controls for health behaviors, social networks, and prior health status. Religious attendance remains significantly associated with lower mortality even after controlling for prior self-assessed health status, but the coefficient is substantially reduced. Other aspects of religiosity are only sporadically associated with health and, in all cases, private religious practices and stronger beliefs are associated with worse health; again, this relationship disappears after controlling for prior health status. These results suggest that reverse causality may partly account for both the positive and negative correlations between religiosity and health. We find no significant associations between religious involvement and biological markers. Notably, even after controlling for prior health, participation in social activities has a more robust effect on health than religious attendance. Consequently, we question whether the purported health benefits are attributable to religion or to social activity in general.

Determinants of old-age mortality in Taiwan.

Relationships among socio-demographic characteristics, general assessments of health, and old-age mortality have been well established in developed countries. There is also increasing focus on the connection between early-life experiences and late-life health. This study tests these and other associations using representative survey data from Taiwan. Survey data on the 60 and over population (N = 4049) in 1989, 1993, and 1996 are linked to 1989-1999 data from a national death registry. Survival is modeled using Gompertz regression and both fixed and time-varying covariates. Possible effects of Taiwan's Universal Health Insurance Program are tested by coding observations as pre- or post-insurance. Some results replicate findings from developed countries; others are new. Contemporaneous education effects on survival are attenuated after introducing some indicators of health from a previous period. Functional and global assessments of health have stronger associations with survival than reports of other health-related characteristics. Mainlanders have higher survival than others. Increases in survival over the 1990s were concentrated among those with the greatest number and severity of functional limitations. This pattern may be an indication of better access to health care or changes in longer-run, but unmeasured, determinants of old-age mortality.

Stability and change in the perceived social support of older Taiwanese adults.

OBJECTIVE: The purpose of this study is to examine stability and change in Taiwanese elders' perceptions about the availability of social support and the sociodemographic and cultural factors associated with change. METHODS: This study uses data from four waves of the Survey of Living Status of the Elderly in Taiwan that spans a 10-year period and employs latent growth curve models to examine trajectories of perceived support and the sociocultural factors that may explain variability in baseline levels of support and variability in changes in support as respondents age. RESULT: Perceptions about social support appear to follow a linear trajectory across age, with significant variation in baseline perceptions and in patterns of change in perceived support across the sample. Sociocultural factors primarily explain differences in initial levels of support but also have some effect on changes in support. DISCUSSION: Despite the increasing pressures and demands on adult children's time that are associated with social and economic development, the elderly in Taiwan on average feel supported by their social networks, with the perceived availability of support increasing with age.

High incidence of JC viruria in JC-seropositive older individuals.

The prevalence of the human JC virus (JCV) in the general population at various ages was investigated. Polymerase chain reaction was employed to detect viral DNA in the urine. The results showed that the incidence of JC viruria was low in the young population, but it was high in the elderly. Hemagglutination inhibition assay was performed for JCV seroprevalence study. The results showed that the seropositive rate of JCV was lower in children than that in adults. The ratio of viruria to seropositive for JCV increased with age and reached 79.7% for those older than 70 years. The results indicated that aging immunity may correlate with JCV reactivation.

Blood-sample processing for the study of age-dependent gene expression in peripheral blood mononuclear cells.

Although most new biogerontological studies seeking to identify longevity candidate genes and factors involved in successful human aging are population based, and likely to involve the collection of blood from extremely old individuals, to our knowledge no unified protocols have yet been published to describe a methodology permitting the simultaneous generation of different kinds of biological specimens derived from a single source of a very small volume of peripheral blood. Here we describe a method permitting the simultaneous generation of plasma, RNA, DNA, protein, fixed lymphocytes, and frozen blood aliquots from a single 10- to 30-ml blood sample obtained from donors of any age (10-102 years old), and we show that the quality and quantity of DNA, RNA, protein, and fixed lymphocytes obtained do not vary significantly with age. As is frequently observed, the older individuals have higher plasma proportions.

Whose education counts? The added impact of adult-child education on physical functioning of older taiwanese.

OBJECTIVES: Research has implicated education as an important predictor of physical functioning in old age. Older adults in Taiwan tend to experience tight familial integration and high rates of adult-child coresidency-much more so than is typical in Western cultures-which might imply additional influences stemming from the education of children. This could arise in a number of ways; for instance, through the sharing of health-related information between child and parent, the quality of caregiving efforts, monetary assistance for medical and other services, or other psychosocial avenues. Despite this probable association, such hypotheses have rarely been tested. In this study, a nationally representative survey of older Taiwanese was used to examine these concurrent effects. METHODS: Outcome variables include the existence of any functional limitations (dichotomously measured) and the severity of functional disorders (ordinally measured). Dichotomous and ordinal logistic models were used. RESULTS: Results suggest that, after adjusting for age, sex, and other factors, both child and respondent education associate with the existence of limitations, but the child's education is more important than the parent's when predicting severity of limitations. DISCUSSION: This implies that models ignoring social network characteristics in determining health outcomes of older adults may be misspecified, at least in some non-Western societies, and calls for further testing in other societies as well.