Multiple Measures of Mineral Metabolism Were Associated With Renal Function in Chinese Centenarians: A Cross-Sectional Study.

Background: Chronic kidney disease (CKD) constitutes a public health issue that is estimated to affect more than 10% of global population. Over 100 million people have CKD in China. For the first time, this cross-sectional study was designed to determine whether multiple measures of mineral metabolism had a significant association with renal function in Chinese centenarians. Methods: China Hainan Centenarian Cohort Study was conducted in 18 cities and counties of Hainan Province, China. It utilized the standard methodology for home interview and blood analyses in 750 centenarians including 608 females and 142 males. Results: All centenarians have a median (range) age of 102 (100-115) years, and median (range) level of estimated glomerular filtration rate (eGFR) was 63 (16-138) ml/min/1.73 m2. There were 318 centenarians (42.4%) with eGFR levels <60 ml/min/1.73 m2. In simple correlation and multivariate linear regression analyses, serum phosphorus, osteocalcin, ß-crosslaps, total procollagen type 1 N-terminal propeptide (TP1NP), and parathyroid hormone (PTH) levels were negatively associated with eGFR levels (P < 0.05 for all). Conclusion: The current study supported that serum phosphorus, osteocalcin, ß-crosslaps, TP1NP, and PTH levels were negatively associated with eGFR levels, and demonstrated a significant association between multiple measures of mineral metabolism and renal function in Chinese centenarians.

The practicality of different eGFR equations in centenarians and near-centenarians: which equation should we choose?

BACKGROUND: No studies have examined the practicality of the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiological Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations for the estimated glomerular filtration rate (eGFR) in a large sample of centenarians. We aim to investigate the differences among the equations and suggest the most suitable equation for centenarians and near-centenarians. METHODS: A total of 966 centenarians and 787 near-centenarians were enrolled, and the eGFR was calculated using the three equations mentioned above. Agreement among the equations was investigated with the κ statistic and Bland-Altman plots. Sources of discrepancy were investigated using a partial correlation analysis. RESULTS: The three equations for assessing eGFR are not considered interchangeable in centenarians and near-centenarians. Δ(MDRD, CKD-EPI) and Δ(MDRD, BIS1) increased with age, but Δ(CKD-EPI, BIS1) was relatively stable with age. Δ(MDRD, CKD-EPI) and Δ(MDRD, BIS1) were considerable in subjects with Scr levels less than 0.7 mg/dL and decreased with the Scr level. A considerable difference between CKD-EPI and BIS1 was observed for participants with Scr levels ranging from 0.5 to 1.5 mg/dL. This difference increased with Scr levels ranging from 0.5 to 0.7 mg/dL, was relatively stable for Scr levels ranging from 0.7 to 0.9 mg/dL, and decreased with Scr levels ranging from 0.9 to 1.5 mg/dL. The differences in the three comparisons were all greater in women than in men (p < 0.05). CONCLUSIONS: We tend to suggest the MDRD equation to calculate the glomerular filtration rate (GFR) in elderly individuals >95 years old who have no risk factors for cardiovascular disease; the BIS1 equation to calculate the eGFR for elderly individuals younger than 94 years old who have risk factors for cardiovascular disease; the CKD-EPI equation to calculate the eGFR of elderly individuals with Scr levels greater than 1.5 mg/dL; and the BIS1 equation to calculate the eGFR of older women with Scr levels less than 0.7 mg/dL.

Oestradiol: any role in cardiovascular risk factors in female centenarians of Hainan?

BACKGROUND: Previous studies reported that low level of oestradiol (E2) was associated with higher risk of cardiovascular disease (CVD). However, little study examined the relationship between E2 and CVD in longevous women, which were deficient in serum E2 for the post-menopausal status. Therefore, this study aims to explore the association between E2 and CVD risk factors in a group of female centenarians of Hainan, China. METHODS: A total of 413 female centenarians (aged from 100 to 115) from China Hainan Centenarian Cohort Study (CHCCS) were enrolled in this study. Home interviews were conducted to collected data on demographic characteristics, health-related lifestyles, and anthropometrics. The level of serum E2 was assessed in the Clinical Laboratory of Hainan branch of PLA General Hospital. The variables of CVD risk factors, including blood pressures, lipids and blood glucose, were measured through standard procedures. RESULTS: Significant negative correlations between levels of serum E2 and TC, HDL-C, and LDL-C were observed in this study. Compared with the highest group of E2, the odds ratio and 95% confidence intervals of high LDL-C in groups 3, 2 and 1 were OR1.94 (CI0.82-4.62), OR3.61 (CI1.27-10.25) and OR9.29 (CI2.08-41.53), respectively. Similarly, the prevalence of hypertension was decreased with the increase of serum E2. The odds ratio and 95% confidence intervals of stage-2 hypertension in groups 3, 2 and 1 versus highest E2 group were OR1.34 (CI0.49-3.72), OR1.36 (CI0.47-3.99) and OR1.38 (CI0.45-4.20), respectively. CONCLUSIONS: This study examined the relationship between E2 and CVD risk factors in a group of community-based female centenarians. A negative correlations between serum E2 levels and CVD risk factors, i.e. high level of LDL-C, TC, and hypertension were observed in this population. Besides, the level of serum E2 is also negatively correlated with HDL-C. Further studies on the correlation between serum E2 and CVD risk factors, especially dyslipidemia, in longevous and post-menopausal women are warranted.

Analysis of chronic kidney disease staging with different estimated glomerular filtration rate equations in Chinese centenarians.

BACKGROUND: Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy. METHODS: A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the κ statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis. RESULTS: The κ values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P < 0.001). CONCLUSIONS: The strengths of agreement between the MDRD and CKD-EPI equations were substantial, but those between the MDRD and BIS1 equations and the CKD-EPI and BIS1 equations were fair. The difference in CKD staging of the first 2 comparisons strongly depended on Scr, SUA and gender, and that of CKD-EPI and BIS1 equations strongly depended on Scr and gender. The incidence at various stages of CKD staging was quite different. Thus, a new equation that is more suitable for the elderly needs to be built in the future.

Risk Factors For Hyperuricemia In Chinese Centenarians And Near-Centenarians.

PURPOSE: Hyperuricemia is an important potential pathogenic factor for hypertension, cardiovascular disease and stroke. The current study aimed to investigate the prevalence of hyperuricemia and its relationship to lifestyle characteristics and dietary habits in centenarians and near-centenarians. PATIENTS AND METHODS: In total, 966 centenarians and 788 near-centenarians were included. Community-based surveys were conducted to collect information about lifestyle. Blood examinations were performed using enzymatic assays. T-tests and χ2 tests were used to investigate significant indicators of hyperuricemia, and multivariate logistic regression was used to analyze the related risk factors. A comprehensive analysis of nineteen modifiable factors, including lifestyle characteristics, dietary habits, general characteristics and blood test indexes, was conducted. RESULTS: The prevalence of hyperuricemia was 29.02%. The percentage of men, waist circumference (WC), waist-hip ratio, estimated glomerular filtration rate (eGFR), levels of total protein (TP), alanine aminotransferase, aspartate aminotransferase, triglycerides, high-density lipoprotein cholesterol, serum homocysteine, serum uric acid, serum urea and serum creatinine, passive smoking, alcohol consumption, snoring, preference for fried flavors, and meat, seafood and vegetable consumption were significantly different between the hyperuricemia group and the normouricemia group (p<0.05). Multivariate logistic regression analysis showed that WC (OR=1.020), eGFR (OR=0.960), TP level (OR=1.038), serum urea level (OR=1.154), passive smoking (OR=2.589), snoring (OR=2.003), meat consumption (OR=2.506), seafood consumption (OR=1.422) and vegetable consumption (OR=0.521) were significantly associated with the risk of hyperuricemia (p<0.05). CONCLUSION: Low eGFR and vegetable consumption, high WC, TP, and serum urea levels, passive smoking, snoring, and high meat and seafood consumption were independent risk factors for hyperuricemia. It is recommended that people at high risk for hyperuricemia should actively limit their intake of fried food, alcohol and purine-rich food, increase their intake of fresh vegetables, actively treat sleep apnea syndrome, avoid passive smoking, maintain a healthy WC and seek to improve their kidney and liver function.

Associations of immunological factors with metabolic syndrome and its characteristic elements in Chinese centenarians.

BACKGROUND: Metabolic syndrome (MetS) has an increased prevalence (approximately 20-25% of the adult population) all over the world. Immunological function is significantly associated with the development of MetS, and MetS is beginning to be considered as a chronic immune-related disease. The present study addressed on the associations of immunological factors with MetS and its characteristic elements in Chinese centenarians. METHODS: Hainan is a longevity region with the highest population density of centenarians in China. The China Hainan Centenarian Cohort Study has a considerable sample size, and provides a significant population-based sample of centenarians. Home interview, physical examination and blood analysis were conducted following standard procedures. RESULTS: All centenarians had a median age of 102 (100-115) years, and the proportion of females was 80.8%. The proportion of centenarians with MetS was 16.0% (135 centenarians). Abdominal obesity, hypertension, dyslipidemia and diabetes mellitus had a prevalence of 26.4% (223 centenarians), 73.7% (623 centenarians), 40.4% (341 centenarians) and 10.7% (90 centenarians), respectively. In Logistic regression analyses, MetS was significantly associated with immunoglobulin E and complement C3 levels (P < 0.05 for all). Abdominal obesity was significantly associated with immunoglobulin E and complement C3 levels (P < 0.05 for all). CONCLUSIONS: The present study provides epidemiological evidence that MetS has significant associations with immunoglobulin E and complement C3 levels, and demonstrates that abdominal obesity is significantly associated with immunoglobulin E and complement C3 levels in Chinese centenarians.

Prevalence of functional dependence in Chinese centenarians and its relationship with serum vitamin D status.

BACKGROUND: Functional dependence (FD) and vitamin D deficiency are common conditions in older adults. However, little is known about the relationship between FD and serum vitamin D status in centenarians. The current study was designed to evaluate the prevalence of FD and examine its relationship with serum vitamin D status among centenarians in China. SUBJECTS AND METHODS: A cross-sectional study of a large sample of Chinese centenarians including 180 men and 822 women was conducted from June 2014 to December 2016. Home interviews, physical examinations, and blood analyses were performed in 958 centenarians following standard procedures. FD was evaluated using the Barthel index of activities of daily living (ADL). Serum 25-hydroxyvitamin D (25OHD) concentrations were measured as a marker of vitamin D status. RESULTS: The prevalence of centenarians with FD was 71.2%. Vitamin D deficiency, lack of tea consumption, lack of outdoor activities, visual impairment, and fracture were predictors of FD. Centenarians in the lowest quartile of serum 25OHD concentration had an approximately threefold greater likelihood of FD than those in the highest quartile in multiple logistic regression models (OR =2.88; 95% CI 1.75-4.73; P<0.001). The multivariable OR with a 1 ng/mL decrease in serum 25OHD concentration was 1.06 (95% CI 1.04-1.08; P<0.001) for FD. CONCLUSION: Serum 25OHD levels have important associations with FD in Chinese centenarians. Future research could focus on the value of intervening in the case of low serum 25OHD levels through vitamin D supplementation and improving ADL in the older population.

Relationships of Hyperhomocysteinemia and Hyperuricemia With Metabolic Syndrome and Renal Function in Chinese Centenarians.

As the first time worldwide, this study aimed to investigate the relationships of hyperhomocysteinemia and hyperuricemia with metabolic syndrome (MetS) and renal function in Chinese centenarians. The China Hainan Centenarian Cohort Study was performed in 18 cities and counties of the Hainan Province. Home interview, physical examination, and blood analysis were performed on 808 centenarians following standard procedures. All centenarians had a median age of 102 (100-115) years. Prevalence of hyperhomocysteinemia and hyperuricemia was 91.6% (740 centenarians) and 28.5% (230 centenarians), respectively. The MetS was present in 117 centenarians (14.5%). In simple correlation analyses, hyperhomocysteinemia and hyperuricemia were significantly correlated with MetS and glomerular filtration rate (GFR) < 60 ml/min/1.73 m2 (P < 0.05 for all). Serum homocysteine levels were significantly correlated with GFR, waist circumference (WC), and triglyceride levels, while serum uric acid levels were significantly correlated with these variables plus high-density lipoprotein cholesterol (HDL-C) levels (P < 0.05 for all). In logistic regression analyses, hyperhomocysteinemia and hyperuricemia were significantly associated with MetS and GFR < 60 ml/min/1.73 m2 (P < 0.05 for all). In linear regression analyses, serum homocysteine levels were significantly associated with GFR, WC, and triglyceride, while serum uric acid levels were significantly associated with these variables plus HDL-C (P < 0.05 for all). Both hyperhomocysteinemia and hyperuricemia had important relationships with MetS and renal function in Chinese centenarians. Hyperuricemia and hyperhomocysteinemia that could help identify, while also affecting, the development of MetS and renal function may unfold complex relationships between MetS, renal function, and cardiovascular risk and provide effective prevention strategies for these conditions.

The prevalence of depressive symptoms in Chinese longevous persons and its correlation with vitamin D status.

BACKGROUND: Hypovitaminosis D and depressive syndromes are common conditions in old adults. However, little is known about the relationship between vitamin D and depression in exceptional aged people. The objective of this study is to evaluate the relationship between vitamin D levels and depressive symptoms in Chinese longevous persons. METHODS: We used a dataset from a cross-sectional survey of a sample of Chinese longevous people with self-reported age 100 or older, including 175 men and 765 women, was conducted from June 2014 to December 2016 in Hainan Province, China. Data on demographics, lifestyle characteristics and health conditions were collected using a structured questionnaire. Anthropometrics and blood samples were obtained following the standard procedure. Depressive symptoms of the participants were assessed using a shortened version of the Geriatric Depression Scale (GDS-15). Serum vitamin D levels were measured using an automated radioimmunoassay. RESULTS: The prevalence of longevous persons with depressive symptoms among the sample was 32.2% (95% confidence interval: 29.7-34.7%). Serum vitamin D levels were lower in participants with depressive symptoms than in those without (20.8 ± 8.7 vs. 23.7 ± 9.7, ng/mL). Vitamin D deficiency was an independent risk factor for depression after controlling for the potential covariates (Odds ratio = 1.47, 95% Confidence interval = 1.08-2.00; p = 0.014). A negative relationship between serum vitamin D levels and depressive symptoms was also detected, and the relationship remained significant after adjusting for a wide range of other covariates. The multivariate adjusted odds ratio of depressive symptoms for the lowest versus highest quartiles of vitamin D levels was 1.73 (95% confidence interval: 1.10-2.72), and the adjusted odds ratio with a 5 ng/mL decrement of serum 25OHD levels was 1.10 (95% confidence interval: 1.01-1.19). CONCLUSIONS: This study showed an inverse association between vitamin D levels and depressive symptoms among Chinese longevous persons. Depressive symptoms should be screened in longevous persons who had vitamin D deficiency. Further studies on vitamin D supplement and prevention along with treatment of depression are needed among very old population.

Prevalence of metabolic syndrome risk factors and their relationships with renal function in Chinese centenarians.

As the first time, this study was to investigate the prevalence of metabolic syndrome (MetS) risk factors and explore their relationships with renal function in Chinese centenarians. China Hainan Centenarian Cohort Study was performed in 18 cities and counties of Hainan Province. Home interview, physical examination and blood analysis were performed in 874 centenarians following standard procedures. Prevalence of MetS was 15.6% (136 centenarians). There were 229 centenarians with abdominal obesity (26.2%), 645 centenarians (73.8%) with hypertension, 349 centenarians with dyslipidemia (39.9%) and 92 centenarians with diabetes mellitus (10.5%). In multivariate linear regression, age, smoking, waist circumstance (WC), systolic blood pressure (SBP) and triglyceride levels were inversely and diastolic blood pressure (DBP) levels were positively associated with glomerular filtration rate levels (P < 0.05 for all). This study reported low prevalence of MetS risk factors and demonstrated that age, smoking, abdominal obesity (WC), hypertension (SBP and DBP) and triglyceride levels were independently associated with renal function in Chinese centenarians. This study provided reliable data about Chinese centenarians, analyzed significant relationships between Mets risk factors and renal function, and explained possible reason (low prevalence of MetS and its risk factors) and mechanism (interrelationship of age, Mets risk factors with renal function) of longevity.

Association between anthropometric measures and cardiovascular disease (CVD) risk factors in Hainan centenarians: investigation based on the Centenarian's health study.

BACKGROUND: Centenarians refer to a special group who have outlived most of their fellows. Body shape and abdominal obesity have been identified as cardiovascular disease (CVD) risk factors. Our study aimed to evaluate the relationship between body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) and CVD risk factors among male and female centenarians in Hainan province. METHODS: Five hundred thirty-seven centenarians aged between 100 and 115 (Mage = 107 years old) years participated in this study. Each participant received a standardized questionnaire and physical examination. We measured anthropometric variables (BMI, WC, WHR, WHtR, SBP and DBP) and serum lipid (TC, TG, HDL-C and LDL-C). RESULTS: 76.9% (n = 413) of the study subjects were female. TC, TG, LDL-C and HDL-C were significantly higher in female group than that of male group. BMI, WC and WHtR were well-correlated with the CVD risk factors. The anthropometric measures were negatively related with HDL-C levels and positively related with the other CVD risk factors. CONCLUSIONS: Hainan centenarians were short in stature and underweight. Moreover, female centenarians were often pear-shaped, while male centenarians were often apple-shaped. Further, BMI, WC and WHtR were well-correlated with the serum lipid, and TC, TG, LDL-C and HDL-C were significantly higher in females than males. Also, BMI, WC and WHtR were closely related to the incidence of dyslipidemia in females, including high TG, high LDL-C and low HDL-C.

Thyroid nodules in centenarians: prevalence and relationship to lifestyle characteristics and dietary habits.

BACKGROUND: Thyroid nodules (TNs) are common thyroid lesions in older population. Few studies have focused on the prevalence of TNs and their relationship to lifestyle characteristics and dietary habits in centenarians. The current study aimed at determining the prevalence of TNs in Chinese centenarians by using high-resolution ultrasound (US) equipment and at investigating its relationship to lifestyle characteristics and dietary habits. PARTICIPANTS AND METHODS: The current study was part of the China Hainan Centenarian Cohort Study that was conducted in Hainan, an iodine-sufficient region in People's Republic of China. A total of 874 permanent residents aged ≥100 years (mean age =102.8±2.8 years) without any missing data were included in the analysis. RESULTS: Among the participants, 649 of them were detected at least one TN under the US examinations. The overall prevalence rate of TNs was 74.3%. The prevalence of TNs was higher in participants who were women, had hypertension, had diabetes, and were underweight compared with their counterparts. Multivariate logistic regression analyses showed that being female, hypertensive, and diabetic; betel quid consumption; and red meat consumption were independent risk factors, while being underweight and nut consumption were independent protective factors for TNs. CONCLUSION: Our findings indicate that the presence of TNs was highly prevalent in Chinese centenarians, particularly in women. In addition to gender, having hypertension, having diabetes, and being underweight, the presence of TNs was independently associated with betel quid, red meat, and nut consumption. Further prospective studies are warranted to verify these associations in populations from different age strata, races, cultures, and iodine supplementation.

Methylation of the genes ROD1, NLRC5, and HKR1 is associated with aging in Hainan centenarians.

BACKGROUND: Human aging is a hot topic in biology, and it has been associated with DNA methylation changes at specific genomic sites. We aimed to study the changes of DNA methylation at a single-CpG-site resolution using peripheral blood samples from centenarians. METHODS: Using Illumina 450 K Methylation BeadChip microarray assays, we carried out a pool-based, epigenome-wide investigation of DNA methylation of blood samples from 12 centenarians and 12 healthy controls. Differentially methylated cytosine-phosphate-guanosine (CpG) sites were selected for further pyrosequencing analysis of blood samples from 30 centenarians and 30 healthy controls. RESULT: We identified a total of 31 high-confidence CpG sites with differential methylation profiles between the groups: 9 (29%) were hypermethylated and 22 (71%) were hypomethylated in centenarians. It was also found that hypermethylation of HKR1 and hypomethylation of ROD1 and NLRC5 genes strongly correlated with age in centenarians. CONCLUSION: Our results indicate that the methylation profile combination of HKR1, ROD1, and NLRC5 could be a promising biomarker for aging in Hainan centenarians.

A survey on hearing acuity of centenarians in Hainan Province.

OBJECTIVE: This study aimed to investigate hearing acuity of centenarians in Hainan Province and provide basis for interventional considerations. METHOD: Door-to-door follow-up was conducted to investigate hearing acuity of centenarians (aged 100 years or above) in Hainan Province. Physical examination, pure tone audiometry and acoustic impedance test were performed, and the results were analyzed. RESULT: A total of 460 centenarians (920 ears) were tested by pure tone audiometry. The rate of normal hearing was 0.2%, the rate of mild hearing loss was 1.5%, 12% for moderate hearing loss, 33.9% for moderate to severe hearing loss, 37.4% for severe hearing loss is and 15% for profound hearing loss. Acoustic impedance test was performed in 340 centenarians (668 ears). Tympanogram was type A in 41.2% of the ears, type As in 34.1% ears, type Ad in 6.4%, type B in 11.8%, and type C in 4.9% of the ears, while no response was elicited in 1.5% of the ears. CONCLUSION: Age related sensorineural hearing loss is prevalent among centenarians in Hainan Province. A probably beneficial intervention may be the use of hearing aids for effective communication.

Mesenchymal stem cell-conditioned medium accelerates wound healing with fewer scars.

Mesenchymal stem cells (MSCs) derived from umbilical cords (UC-MSCs) have been shown to enhance cutaneous wound healing by means of the paracrine activity. Fibroblasts are the primary cells involved in wound repair. The paracrine effects of UC-MSCs on dermal fibroblasts have not been fully explored in vitro or in vivo. Dermal fibroblasts were treated with conditioned media from UC-MSCs (UC-MSC-CM). In this model, UC-MSC-CM increased the proliferation and migration of dermal fibroblasts. Moreover, adult dermal fibroblasts transitioned into a phenotype with a low myofibroblast formation capacity, a decreased ratio of transforming growth factor-ß1,3 (TGF-ß1/3) and an increased ratio of matrix metalloproteinase/tissue inhibitor of metalloproteinases (MMP/TIMP). Additionally, UC-MSC-CM-treated wounds showed accelerated healing with fewer scars compared with control groups. These observations suggest that UC-MSC-CM may be a feasible strategy to promote cutaneous repair and a potential means to realise scarless healing.

Epithelial-mesenchymal transition: An emerging target in tissue fibrosis.

Epithelial-mesenchymal transition (EMT) is involved in a variety of tissue fibroses. Fibroblasts/myofibroblasts derived from epithelial cells contribute to the excessive accumulation of fibrous connective tissue in damaged tissue, which can lead to permanent scarring or organ malfunction. Therefore, EMT-related fibrosis cannot be neglected. This review highlights the findings that demonstrate the EMT to be a direct contributor to the fibroblast/myofibroblast population in the development of tissue fibrosis and helps to elucidate EMT-related anti-fibrotic strategies, which may enable the development of therapeutic interventions to suppress EMT and potentially reverse organ fibrosis.