Exploration for the reference interval of C-reactive protein in the Chinese longevity people over 90 years of age.

BACKGROUND: Older individuals tend to develop chronic inflammation. As a commonly used nonspecific inflammatory marker, C-reactive protein (CRP) can predict metabolic syndrome, cardiovascular diseases, etc. However, little is known about CRP levels in longevity people. OBJECTIVES: Investigate the distribution and correlates of CRP and provide a reference for the establishment of normal interval values in Chinese longevity people over 90 years of age. METHODS: We performed a correlation analysis to evaluate the correlation between CRP levels and longevity based on the basic demographic characteristics, anthropometric measurements and blood data of 4,418 participants in the 2015 China Health and Retirement Longitudinal Study and 636 participants in an ongoing longitudinal study of natural longevity people in Guangxi. On this basis, the CRP reference interval for longevity was explored. RESULTS: The CRP concentration was significantly different among the three age groups, with a median of 3.80 mg/L for those older than 90 years, which was significantly higher than that for those aged 45-64 years (median 1.20 mg/L, p < 0.001) and 65-89 years (median 1.30 mg/L, p < 0.001). Body mass index, waist circumference, the waist-to-height ratio, systolic blood pressure, diastolic blood pressure, and fasting and postprandial blood glucose, triglyceride, total cholesterol and low-density lipoprotein cholesterol levels were positively correlated with CRP levels, while fasting high-density lipoprotein cholesterol was negatively correlated with CRP levels. The CRP reference interval (RI) value in longevity people was 0.25-9.22 mg/L. CONCLUSION: The concentrations of CRP increased with advancing age, and the CRP reference interval was different between older and younger adults.

Facilely Control Grafting Density and Side Chain Composition of Bottlebrush Polymer.

Control over polymer architecture and composition is essential for disclosing structure-property relationships and developing high-performance materials. Herein, a new method is successfully developed to synthesize bottlebrush polymer (BP) with controllable graft density and side chain composition by "grafting-from" strategy using in situ halogen exchange and reversible chain transfer catalyzed polymerization (RTCP). The main chain of the BP is first synthesized by the polymerization of methacrylates containing alkyl bromide as a side group. Then, the alkyl bromine is quantitatively converted to alkyl iodide with sodium iodide (NaI) via in situ halogen exchange to efficiently initiate the RTCP of methacrylates. By adjusting the input amount of NaI and monomers in sequence, BP named PBPEMA-g-PMMA/PBzMA/PPEGMEMA which contains three different kinds of polymer side chains including hydrophilic PPEGMEMA, hydrophobic PMMA, and PBzMA is synthesized with narrow molecular weight distribution (Mw /Mn  ≤ 1.36). The grafting density and the chain length of each polymer side chain are well controlled by the addition of NaI in batches and following RTCP. Moreover, the obtained BP self-assembled into spherical vesicles in aqueous with hydrophilic coronal structure, core region, and the hydrophobic wall between the former two, which enables to wrap hydrophobic pyrene and hydrophilic Rhodamine 6G separately or simultaneously.

The relationship between sleep duration and activities of daily living (ADL) disability in the Chinese oldest-old: A cross-sectional study.

Objective: To investigate the relationship between sleep duration and activities of daily living (ADL) disability, and to explore the optimal sleep duration among oldest-old Chinese individuals. Methods: In this cross-sectional study, 1,798 participants (73.2% female) were recruited from Dongxing and Shanglin in Guangxi Zhuang Autonomous Region, China in 2019. The restricted cubic spline function was used to assess the dose-response relationship between sleep duration and ADL disability, and the odds ratios (ORs) of the associations were estimated by logistic regression models. Results: The overall prevalence of ADL disability was 63% (64% in females and 58% in males). The prevalence was 71% in the Han population (72% in females and 68% in males), 60% in the Zhuang population (62% in females and 54% in males) and 53% in other ethnic population (53% in females and 53% in males). A nonlinear relationship between sleep duration and ADL disability was observed. Sleep duration of 8-10 hours was associated with the lowest risk of ADL disability. Sleep duration (≥12 hours) was associated with the risk of ADL disability among the oldest-old individuals after adjusting for confounding factors (OR = 1.47, 95% CI [1.02, 2.10], p < 0.05). Conclusion: Sleep duration more than 12 hours may be associated with an increased risk of ADL disability in the oldest-old individuals, and the optimal sleep duration among this population could be 8-10 h.

The major risk factor for depression in the Chinese middle-aged and elderly population: A cross-sectional study.

Background: The number of patients suffering from depression is continuously increasing in China. Demographic characteristics, physical health levels, and individual lifestyles/healthy behaviors are associated with the severity of depression. However, the major risk factor for depression remains unclear. Materials and methods: In this investigation, 16,512 patients were screened using the CHARLS (China Health and Retirement Longitudinal Study) database after being determined to be eligible based on the inclusion criteria. Depressive symptoms were evaluated through the CESD-10 (10-item Center for Epidemiological Studies Depression Scale). Consequently, various models were developed based on potential predictive factors, employing stepwise LR (Logistic Regression)/RF (Random Forests) models to examine the influence and weighting of candidate factors that affect depression. Results: Gender, residential address location, changes in health status following last interview, physical disabilities, chronic pain, childhood health status, ADL (activity of daily living), and social activity were all revealed to be independent risk factors for depression (p < 0.05) in this study. Depression has a synergic effect (across chronic pain and age groups). In comparison to other factors, RF results showed that chronic pain had a stronger impact on depression. Conclusion: This preliminary study reveals that chronic pain is a major risk factor for depression.

The general law of plasma proteome alterations occurring in the lifetime of Chinese individuals reveals the importance of immunity.

BACKGROUND: Aging is characterized by a continuous loss of protein homeostasis. A closer examination of peripheral blood, which houses proteins from nearly all tissues and cells, helped identify several biomarkers and other aspects of aging biology. To further explore the general law of aging and identify key time nodes and associated aging biology, we collected 97 plasma samples from 253 healthy individuals aged 0-100 years without adverse outcomes to conduct nano-Ultra High Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (nano-UHPLC-MS/MS) and weighted gene co-expression network analysis (WGCNA). RESULTS: Through biological processes and key biological pathways identified in discrete age group modules, our analyses highlighted a strong correlation between alterations in the immune system and aging process. We also identified hub genes associated with distinct age groups that revealed alterations not only in protein expression but also in signaling cascade. Among them, hub genes from age groups of 0-20 years old and 71-100 years old are mostly involved in infectious diseases and the immune system. In addition, CDC5L and HMGB2 were the key transcription factors (TFs) regulating genes expression in people aged between 51-60 and 71-100 years of age. They were shown to not only be independent but also mutually regulate certain hub gene expressions. CONCLUSIONS: This study reveals that the plasma proteome undergoes a complex alteration over the lifetime of a human. In this process, the immune system is crucial throughout the lifespan of a human being. However, the underlying mechanism(s) regulating differential protein expressions at distinct ages remains to be elucidated.

The roles of cell-cell and organ-organ crosstalk in the type 2 diabetes mellitus associated inflammatory microenvironment.

Type 2 diabetes mellitus (T2DM) is a classic metaflammatory disease, and the inflammatory states of the pancreatic islet and insulin target organs have been well confirmed. However, abundant evidence demonstrates that there are countless connections between these organs in the presence of a low degree of inflammation. In this review, we focus on cell-cell crosstalk among local cells in the islet and organ-organ crosstalk among insulin-related organs. In contrast to that in acute inflammation, macrophages are the dominant immune cells causing inflammation in the islets and insulin target organs in T2DM. In the inflammatory microenvironment (IME) of the islet, cell-cell crosstalk involving local macrophage polarization and proinflammatory cytokine production impair insulin secretion by ß-cells. Furthermore, organ-organ crosstalk, including the gut-brain-pancreas axis and interactions among insulin-related organs during inflammation, reduces insulin sensitivity and induces endocrine dysfunction. Therefore, this crosstalk ultimately results in a cascade leading to ß-cell dysfunction. These findings could have broad implications for therapies aimed at treating T2DM.

Identification and replication of novel genetic variants of ABO gene to reduce the incidence of diseases and promote longevity by modulating lipid homeostasis.

Genes related to human longevity have not been studied so far, and need to be investigated thoroughly. This study aims to explore the relationship among ABO gene variants, lipid levels, and longevity phenotype in individuals (≥90yrs old) without adverse outcomes. A genotype-phenotype study was performed based on 5803 longevity subjects and 7026 younger controls from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). Four ABO gene variants associated with healthy longevity (rs8176719 C, rs687621 G, rs643434 A, and rs505922 C) were identified and replicated in the CLHLS GWAS data analysis and found significantly higher in longevity individuals than controls. The Bonferroni adjusted p-value and OR range were 0.013-0.020 and 1.126-1.151, respectively. According to the results of linkage disequilibrium (LD) analysis, the above four variants formed a block on the ABO gene (D'=1, r2range = 0.585-0.995). The carriers with genotypes rs687621 GG, rs643434 AX, or rs505922 CX (prange = 2.728 x 10-107-5.940 x 10-14; ORrange = 1.004-4.354) and haplotype CGAC/XGXX (p = 2.557 x 10-27; OR = 2.255) had a substantial connection with longevity, according to the results of genetic model analysis. Following the genotype and metabolic phenotype analysis, it has been shown that the longevity individuals with rs687621 GG, rs643434 AX, and rs505922 CX had a positive association with HDL-c, LDL-c, TC, TG (prange = 2.200 x 10-5-0.036, ORrange = 1.546-1.709), and BMI normal level (prange = 2.690 x 10-4-0.026, ORrange = 1.530-1.997). Finally, two pathways involving vWF/ADAMTS13 and the inflammatory markers (sE-selectin/ICAM1) that co-regulated lipid levels by glycosylation and effects on each other were speculated. In conclusion, the association between the identified longevity-associated ABO variants and better health lipid profile was elucidated, thus the findings can help in maintaining normal lipid metabolic phenotypes in the longevity population.

Association between IL-1B (-511)/IL-1RN (VNTR) polymorphisms and type 2 diabetes: a systematic review and meta-analysis.

Interleukin-1 (IL-1) plays an essential role in the immune pro-inflammatory process, which is regarded as one of many factors in the development of type 2 diabetes mellitus (T2DM). Several case-control studies have illustrated the association of the IL-1B (-511) (rs16944, Chr 2:112,837,290, C/T Intragenic, Transition Substitution) and IL-1RN (VNTR) (gene for IL-1 receptor antagonist, IL-1RA, 86 bp tandem repeats in intron 2) polymorphisms with T2DM risk. However, the results were inconsistent and inconclusive. We performed a meta-analysis (registry number: CRD42021268494) to assess the association of the IL-1B (-511) and IL-1RN (VNTR) polymorphisms with T2DM risk. Random-effects models were applied to calculate the pooled ORs (odds ratios) and 95% CIs (confidence intervals) to test the strength of the association in the overall group and subgroups stratified by ethnicity, respectively. Between-study heterogeneity and publication bias were evaluated by the Q-test, I2 statistic, Harbord test, and Peters test accordingly. Sensitivity analyses were also performed. A total of 12 publications evaluating the association of IL-1B (-511) and IL-1RN (VNTR) polymorphisms with the risk of T2DM development were included. The meta-analysis showed that IL-1RN (VNTR) was related to the increasing development of T2DM risk in the recessive model (OR = 1.62, 95% CI [1.09-2.42], Phet = 0.377, Pz = 0.018) and in the homozygous model (OR = 2.02, 95% CI [1.07-3.83], Phet = 0.085, Pz = 0.031), and the IL-1RN 2* allele was found a significant association with evaluated T2DM risk in all ethnicities (OR = 2.08, 95% CI [1.43-3.02], Phet < 0.001, Pz < 0.001) and in EA (OR = 2.01, 95% CI [1.53-2.66], Phet = 0.541, Pz < 0.001). Moreover, stratification by ethnicity revealed that IL-1B (-511) was associated with a decreased risk of T2DM in the dominant model (OR=0.76, 95% CI [0.59-0.97], Phet = 0.218, P z = 0.027) and codominant model (OR = 0.73, 95% CI [0.54-0.99], Phet = 0.141, Pz = 0.040) in the East Asian (EA) subgroup. Our results suggest that the IL-1RN 2* allele and 2*2* homozygous polymorphism are strongly associated with increasing T2DM risk and that the IL-1B (-511) T allele polymorphism is associated with decreasing T2DM risk in the EA subgroup.

Investigation of the Reference Interval Values of Fasting Plasma Glucose, Blood Pressure, and Blood Lipids in the Longevity People Aged 90 Years Old and Above.

PURPOSE: To our knowledge, the normal fasting plasma glucose (FPG), blood pressure (BP), and blood lipids (BL) interval values have not been well-established in the longevity population. This study aims to provide a reference for the establishment of normal BP, FPG, and BL interval values in the longevity people in China. PATIENTS AND METHODS: A total of 7417 people were selected from the natural longevity cohort in Guangxi, with an age range of 20-110 years old, including 7093 classified as the non-longevity (20-89 years old) (94.02%) and 324 classified as the longevity (≥90 years old) (5.98%); there were 4309 men (58.1%) and 3108 women (41.9%). FPG, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), and low-density lipoprotein (LDL-C) levels were defined as desirable levels when they were below the 75th percentile (P75), borderline levels from the 75th to 90th percentile (P75-P90), and high levels above P90; triglyceride (TG) levels above P90 were defined as high; and high-density lipoprotein cholesterol (HDL-C) levels below the 5th percentile (P5) were defined as low levels. RESULTS: The reference interval values of FPG in the longevity were as follows: desirable levels <6.15 mmol/L, borderline levels 6.15-7.45 mmol/L, high levels ≥7.45 mmol/L. Reference interval values of systolic blood pressure (SBP) were as follows: desirable levels <160.00 mmHg, borderline levels 160.00-174.50 mmHg, high levels ≥175.00 mmHg. DBP reference interval values were as follows: desirable levels <88.00 mmHg, borderline levels 88.00-90.00 mmHg, high levels ≥90.00 mmHg. TC reference interval values were as follows: desirable levels <5.59 mmol/L, borderline levels 5.59-6.45 mmol/L, high levels ≥6.45 mmol/L. LDL-C reference interval values were as follows: desirable levels <3.30 mmol/L, borderline levels 3.30-3.85 mmol/L, high levels ≥3.85 mmol/L. TG reference interval values were as follows: desirable levels <2.82 mmol/L, high levels ≥2.82 mmol/L. HDL-C reference interval values were as follows: low levels <0.80 mmol/L, desirable levels ≥0.80 mmol/L. CONCLUSION: The reference interval values of BP, FPG, and BL are different between the longevity population and the non-longevity population, and the interval values change with increasing age.

A description of the relationship in healthy longevity and aging-related disease: from gene to protein.

Human longevity is a complex phenotype influenced by both genetic and environmental factors. It is also known to be associated with various types of age-related diseases, such as Alzheimer's disease (AD) and cardiovascular disease (CVD). The central dogma of molecular biology demonstrates the conversion of DNA to RNA to the encoded protein. These proteins interact to form complex cell signaling pathways, which perform various biological functions. With prolonged exposure to the environment, the in vivo homeostasis adapts to the changes, and finally, humans adopt the phenotype of longevity or aging-related diseases. In this review, we focus on two different states: longevity and aging-related diseases, including CVD and AD, to discuss the relationship between genetic characteristics, including gene variation, the level of gene expression, regulation of gene expression, the level of protein expression, both genetic and environmental influences and homeostasis based on these phenotypes shown in organisms.

Copper exposure association with prevalence of non-alcoholic fatty liver disease and insulin resistance among US adults (NHANES 2011-2014).

BACKGROUND: Excessive copper (Cu) has risky effect on insulin resistance (IR), oxidative stress and inflammation. Instead, some studies reported serum Cu to be protective for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to reevaluate the evidence for a potential risky correlation of serum Cu to NAFLD in large-scale and non-institutionalized American subjects. METHODS: A cross-sectional study of 3211 subjects was from the National Health and Nutrition Examination Survey (NHANES). Logistic regression and cubic spline-based curve-fitting analyses were used to estimate the independent risky effect of Cu to hepatic steatosis index (HSI), US fatty liver index (USFLI) and NAFLD and their dose-effect relationship. Moreover, this association was analyzed in stratification of HOMA-IR, Metabolic syndrome (MetS) and severity of NAFLD, besides age and gender. RESULTS: The average level of serum Cu was 18.67 µmol/L and the prevalence of NAFLD was 54.53% and 32.60%, respectively defined by HSI and USFLI. Generally, the level of Cu was higher in females than males. Serum Cu was positively associated with higher HSI, USFLI index and risk of NAFLD. In fully adjusted models, compared with the lowest quartile, the risk of NAFLD increased 97% in the highest quartile of Cu. Interestingly, stratified analysis showed that the risky effect of Cu to NAFLD was more prominent in the middle-aged, females and subjects with improved status of IR (lower HOMA-IR and non-Mets) compared with their counterparts. Moreover, we further found that circulating copper was correlated to severity of NAFLD only in males. CONCLUSION: Excess serum Cu is significantly associated with risk of NAFLD, which is prominent in females, middle-aged and subjects with improved status of IR, and seems to be related to the severity of NAFLD, additionally. It is necessary to be cautious of the toxic effect of Cu and prospective cohort and mechanism studies are needed to verify the causal effect of Cu to NAFLD.