Sarcopenia is associated with hypomethylation of TWEAK and increased plasma levels of TWEAK and its downstream inflammatory factor TNF-α in older adults: A case-control study.

BACKGROUND: Sarcopenia is a harmful condition common among older adults for which no treatment is available. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (FN14) are known to play important roles in the pathogenesis of sarcopenia. This study investigated alterations in methylation in TWEAK and Fn14 to identify potential targets for the managing sarcopenia. MATERIALS AND METHODS: Through an epidemiological investigation, we detected methylation of CpG islands (CpGs) in TWEAK and Fn14 in community-dwelling older adult of Xinjiang by bisulfite sequencing. Significant CpGs associated with sarcopenia were selected for detection in 152 older individuals by pyrosequencing. Associations between CpG methylation, plasma inflammatory marker levels, and sarcopenia were analyzed. RESULTS: Of 38 CpGs in TWEAK and 30 CpGs in Fn14 detected in 60 individuals, 6 CpGs showed lower methylation in sarcopenia patients compared with control individuals. In 152 older adults, covariance analysis with adjustment for age, gender, triglyceride level, obesity, diabetes, and hypertension showed that the methylation levels of 6 CpGs (CpG8, CpG12, CpG13, CpG20 and CpG21of TWEAK, and CpG24 of Fn14) were significantly lower in sarcopenia patients than in control individuals. With adjustment for additional confounding factors, covariate variance analysis showed that plasma TWEAK, TNF-α and IL-10 levels in the sarcopenia group were significant higher than those in the control group (P = 0.007, P < 0.001, P = 0.003). Multivariate logistic regression analysis showed that CpG8, CpG13, CpG21, and total methylation of TWEAK (OR = 0.767, 95 % CI = 0.622-0.947; OR = 0.740, 95 % CI = 0.583-0.941; OR = 0.734, 95 % CI = 0.561-0.958; OR = 0.883, 95 % CI = 0.795-0.980) as well as CpG22 and total methylation of Fn14 were significantly associated with sarcopenia (OR = 826, 95 % CI = 0.704-0.968; OR = 0.918, 95 % CI = 0.852-0.989). From partial correlation analysis, plasma TWEAK was correlated with plasma TNF-α (r = 0.172, P = 0.042). CONCLUSION: Sarcopenia is associated with hypomethylation of TWEAK and increased plasma levels of TWEAK and its downstream inflammatory factor TNF-α in a community-dwelling population of older adults in Xinjiang.

Ethnic and geographic variations in multiple chronic conditions among community-dwelling older people in Xinjiang: a cross-sectional study.

BACKGROUND: Multiple chronic conditions (MCC) refer to the presence of two or more chronic diseases. The incidence of MCC is higher in older people, and increases with age. Studies have shown an association between MCC and increased adverse outcome, as well as the higher mortality, decline of physical function, and poor quality of life in older populations. Herein, for the first time we provide the data of ethnic and geographic variations in the prevalence of MCC among community-dwelling older people in Xinjiang, China. METHODS: A multilevel random sampling method was employed to perform an epidemiological survey in community-dwelling older adults in southern, northern, and eastern Xinjiang between January 2019 to December 2019. In total, 87,000 participants volunteered, with a response rate of 96.67%; 490 participants with incomplete data were excluded and data from 86,510 participants were analyzed. RESULTS: Our analysis demonstrated that hypertension (51.5%), obesity (27.0%), diabetes (16.9%), heart disease (8.2%), and anxiety/depression (4.5%) were the five main chronic diseases in Xinjiang. The prevalence of MCC in the population surveyed was 33.4% (95%CI, 33.1-33.7). The prevalence in females was 36.6% (95%CI, 36.1-37), which was higher than that in male (30%,95%CI, 29.5-30.4). The prevalence of MCC in older people aged 60-69, 70-79, 80-89, and ≥ 90 years was 32.7% (95%CI, 32.2-33.3), 34.3% (95%CI, 33.9-34.7), 32.5% (95% CI, 31.7-33.3), and 25.9% (95% CI, 23.5-28.3) respectively. As far as the ethnic group was concerned, the prevalence of MCC in Uygur, Han, Kazak, Hui, and Mongolian was 31.3% (95%CI, 30.9-31.7), 34.4% (95%CI, 33.9-35), 40.4% (95%CI, 39.1-41.8), 40.8% (95%CI, 38.9-42.7), 44.4% (95%CI, 38.1-50.6), respectively. The prevalence of MCC was 32.8% (95%CI, 32.1-33.5), 31.7% (95%CI, 31.2-32.1), 36.0% (95%CI, 35.3-36.7) and 39.2% (95%CI, 38.1-40.3) among uneducated, educated for 1-6, 7-9, and more than 10 years. After adjusting for age, sex, smoking, alcohol consumption, and education by level, the binary logistic analysis showed that, compared with eastern Xinjiang, the risk of MCC in the southern area was increased (odds ratio [OR], 1.418; 95% confidence interval [CI], 1.367-1.471), and it was relatively higher in northern Xinjiang (OR, 2.021; 95% CI, 1.944-2.102). Compared with Uygur, Han, Kazakh, Hui and Mongolian had an increased risk of MCC, which was (OR, 1.075; 95% CI, 1.040-1.111), (OR, 1.414; 95% CI, 1.332-1.501), (OR, 1.515; 95% CI, 1.396-1.644), (OR, 1.566; 95% CI, 1.216-2.017), respectively. CONCLUSIONS: There are ethnic and geographic variations in multiple chronic conditions among community-dwelling older people in Xinjiang. The older adults living in northern and southern Xinjiang and Han, Kazakh, Mongolian and Hui older adults have a higher risk of MCC.

Plasma tumor necrosis factor-α is associated with sarcopenia in elderly individuals residing in agricultural and pastoral areas of Xinjiang, China.

Background: Inflammatory reactions play a significant role in the occurrence and development of sarcopenia. Determining the association between specific cytokines and sarcopenia may reveal the disease's pathophysiological mechanism(s). Accordingly, the present study aimed to investigate the association between sarcopenia and inflammatory cytokines among the elderly natural population in agricultural and pastoral areas of Xinjiang. Methods: We conducted a cross-sectional epidemiological survey of the community-dwelling older people using a multi-stage random sampling method in Mulei County in northern Xinjiang and Luopu County in southern Xinjiang from September 2017 to May 2018. Of the 2,100 participants, the statistical analyses included 1,838 participants with complete data. Comparisons of living habits, disease status, biochemical indexes, and levels of interleukin (IL)-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in sarcopenia and non-sarcopenia participants were made in this study. Results: Our study revealed no significant differences (i.e., P > 0.05) in sex, age, ethnicity, smoking and drinking habits, serum renal function, total cholesterol, and diabetes in the elderly between the sarcopenia and non-sarcopenia groups in Xinjiang. However, triglyceride levels (P = 0.004), hypertension (P = 0.019), and abdominal obesity (P < 0.001) in the sarcopenia group were significantly higher than those in the non-sarcopenia group. Moreover, the levels of IL-10 (P < 0.001), IL-4 (P < 0.001), and TNF-α (P < 0.001) in the sarcopenia group were higher than those in the non-sarcopenia group after adjusting for sex, age, hypertension, blood lipid concentration, and obesity. Furthermore, after adjusting for sex, age, hypertension, obesity, and IL-10, IL-4, and IL-6 levels, an increased TNF-α level was also significantly associated with sarcopenia. Conclusion: The results of the present study suggest that an increased plasma level of TNF-α is significantly associated with sarcopenia among elderly individuals residing in Xinjiang's agricultural and pastoral areas. Further study is still needed to determine the physiological role of "immune aging" in the pathogenesis of sarcopenia.

Heat maps of cardiovascular disease risk factor clustering among community-dwelling older people in Xinjiang: a cross-sectional study.

OBJECTIVE: The clustering of multiple cardiovascular disease (CVD) risk factors (CRFs) increases the risk of CVD prevalence and mortality. Little is known about CRF clustering among community-dwelling older people in Xinjiang. The objective of this study was to explore the prevalence of CRF clustering in this population. DESIGN: Cross-sectional study. SETTING: Xinjiang, China. PARTICIPANTS: Multilevel random sampling was used to survey individuals aged ≥60 in six regions of Xinjiang. In total, 87 000 participants volunteered, with a response rate of 96.67%; 702 participants with incomplete data were excluded and data from 86 298 participants were analysed. OUTCOME MEASURES: The prevalence of smoking, hypertension, diabetes, dyslipidaemia and overweight/obesity was 9.4%, 52.1%, 16.8%, 28.6% and 62.7%, respectively. The prevalence of CRF clusters among people of different ages, regions and ethnic groups differed significantly. The 85.7% of the participants presented at least one CRFs and 55.9% of the participants presented clustering of CRFs. The proportion of CRF clusters tended to be higher in men, 60-69-year-old group, northern Xinjiang and the Kazakh population. After adjusting for age and sex, logistic regression analysis revealed that men, 60-69-year-old group, northern Xinjiang and the Kazakh population were more likely to have clustering of CRFs, compared with their counterparts. CONCLUSIONS: The prevalence of CRFs in the older Xinjiang population is high and their clustering differs by sex, age, region and ethnicity. CRF prevention and management should be active in this population, and strategies to reduce CVD risk based on sex, age, ethnic group and region are warranted.

Geographic and Age Variations in Low Body Mass Index Among Community-Dwelling Older People in Xinjiang: A Cross-Sectional Study.

Background: Studies have shown an association between undernutrition and increased adverse outcome, as well as substantial geographic and age variations in undernutrition. Body mass index (BMI), a core indicator of undernutrition, is easy to measure and reflects the nutritional and health status of the human body. It is a simple and suitable tool for epidemiological investigations in large sample populations. Herein, we provide the first description of geographic and age variations in the prevalence of low BMI among community-dwelling older people in Xinjiang. Methods: From January 2019 to December 2019, using a multi-stage random sampling method, we conducted a cross-sectional epidemiological survey of the community-dwelling older people in Xinjiang at different latitudes. Of the 87,000 participants, the statistical analyses included 86,514 participants with complete data. Results: In Xinjiang, the prevalence of low BMI was 7.7% in the community-dwelling older people. The BMI gradually decreased with increasing age and gradually increased with latitude. The prevalence of low BMI in northern Xinjiang was 5.3%, which was significantly lower than that in eastern (7.7%) and southern (9.3%) Xinjiang. In the 60-69-, 70-79-, 80-89-, and ≥90-year age groups, the prevalence rates of low BMI were 5.8, 7.9, 10.0, and 13.9%, respectively. After adjusting for confounding factors (sex, ethnic group, hypertension, diabetes, hyperlipemia, smoking, and drinking), multivariate logistic regression analysis showed that the odds ratios (95% CI) for low BMI in eastern and southern Xinjiang were 1.165 (1.056-1.285) and 1.400 (1.274-1.538), respectively, compared to northern Xinjiang. The adjusted odds ratios (95% CI) for low BMI in the 70-79-, 80-89-, and ≥90-year age groups were 1.511 (1.39-1.635), 2.233 (2.030-2.456), and 3.003 (2.439-3.696), respectively, compared to the 60-69-year age group. Conclusion: The results of this study revealed geographic and age variations in the prevalence of low BMI in the community-dwelling older people in Xinjiang. The prevalence of low BMI gradually increased as the latitude decreased and as age increased.

Expression Profiles of Six Atherosclerosis-Associated microRNAs That Cluster in Patients with Hyperhomocysteinemia: A Clinical Study.

The aim of this study is to discuss the hypothesis that expression of plasma atherosclerosis-associated microRNAs (miRNAs) in hyperhomocysteinemia (Hhcy) patients could predict the presence of atherosclerosis from different channels. Six plasma miRNAs (miR-145, miR-155, miR-222, miR-133, miR-217, and miR-30) selected for our study have been confirmed as critical gene regulators involved in atherosclerosis and can be steadily determined in plasma. Expression of the above six plasma circulating miRNAs revealed significant upregulation of two miRNAs (miR-133 and miR-217) and downregulation of three miRNAs (miR-145, miR-155, and miR-222). Six candidate miRNAs showed a significant correlation with homocysteine (Hcy) or lipid parameters. The results of this study indicated that miR-217 was further significantly upregulated in Hhcy + ATH groups than in normal control, Hhcy-, and atherosclerosis-alone (ATH) groups and it showed a significant negative correlation with Hcy and triglycerides. More specifically, miR-217 showed the most specific expression patterns in all patients with atherosclerosis (ATH and Hhcy + ATH groups), which may have been a diagnostic value for Hhcy complicated with atherosclerosis, and predicted the progress of atherosclerosis in Hhcy patients effectively.

Expression levels of atherosclerosis-associated miR-143 and miR-145 in the plasma of patients with hyperhomocysteinaemia.

BACKGROUND: An elevated level of homocysteine (Hcy) in the blood is designated hyperhomocysteinaemia (Hhcy) and is regarded as a strong risk factor for the development of atherosclerosis (ATH), although the association remains controversial. Considered to be essential gene expression regulators, micro-RNAs (miRNAs) modulate cardiovascular disease development and thus can be regarded as potential biomarkers and therapeutic targets in atherosclerosis. The aim of the current study is to investigate the expression levels of atherosclerosis-associated miR-143 and miR-145 in Hhcy patients and predict the progress of atherosclerosis in Hhcy patients. METHODS: A total of 100 participants were enrolled and included normal control subjects (NC = 20), hyperhomocysteinaemia alone subjects (Hhcy = 25), hyperhomocysteinaemia and carotid artery atherosclerosis combined subjects (Hhcy + ATH = 30) and patients with standalone carotid artery atherosclerosis (ATH = 25). Plasma Hcy, supplementary biochemical parameters and carotid artery ultrasonography (USG) were measured in all participants. MicroRNA expression levels in the peripheral blood were calculated by real-time reverse transcription-polymerase chain reaction (qRT-PCR). The correlations of miR-143 and miR-145 with Hcy, blood lipid parameters and carotid artery atherosclerotic plaques were evaluated using Pearson's correlation coefficients. Receiver operating characteristic (ROC) curve analyses were performed to evaluate the capacities of miR-143 and miR-145 for the detection of Hhcy and atherosclerosis patients. RESULTS: MiR-143 and miR-145 exhibited trends towards significance with stepwise decreases from the NC to Hhcy groups and then to the Hhcy + ATH and ATH groups. Similar results were observed in the carotid artery plaque group (Hhcy + ATH and ATH grups) compared with the no-plaque group (NC and Hhcy groups). The miR-143 expression level exhibited significant negative correlations with Hcy, total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c). The miR-145 expression level exhibited significant negative correlations with Hcy, TC, triglyceride (TG) and LDL-c. MiR-143 and miR-145 exhibited the greatest area under the curves (AUCs) (0.775 and 0.681, respectively) for the detection of every Hhcy patient, including those in the Hhcy and Hhcy + ATH groups, from among all subjects. CONCLUSION: The results indicated that the levels of atherosclerosis-associated circulating miR-143 and miR-145 are linked to Hhcy. MiR-143 may be used as a potential non-invasive biomarkers of Hhcy and thus may be helpful in predicting the progress of atherosclerosis in Hhcy patients.