Middle-aged Individuals Research Articles

Sources of Happiness According to Life Periods.

This study aimed to explore the sources of happiness of individuals across different stages of their lives. A phenomenological study, which is a qualitative research approach, was designed. The sample consists of 129 participants (62 women, 67 men). Thematic analysis was conducted to analyze the data, and common themes were identified for each life stage. The analysis of the themes revealed that children and adolescents expressed the sources of happiness mostly through hedonic values, whereas individuals in middle adulthood and late middle age predominantly expressed them in eudaimonic values. Sources of happiness in all life stages include the themes of closeness to family, closeness to friends, social relations, altruistic attitudes, social peace, and traveling. In young adulthood and later life stages, the theme of spirituality emerged, including concepts such as the meaning and purpose of life, belief in God, gratitude to God, and being connected with nature. In childhood, the themes of playing games, receiving gifts, and experiencing surprises were prominent sources of happiness, whereas in adolescence, the themes were eating favorite things and achieving autonomy. Health, money, being successful, hope, hobbies, being valued and appreciated were found to be other common sources of happiness across various life stages.

A cohort study reveals shared and distinct serum metabolic biomarkers for major adverse cardiovascular events in middle-aged and older adults.

We assessed the association of serum metabolites with the occurrence of major adverse cardiovascular events (MACE) in middle-aged and elderly individuals, explored the value of metabolomics in predicting MACE, and compared the distinctions in MACE risk-related metabolic biomarkers between middle-aged and elderly groups. Among the participants of the UK Biobank who underwent baseline assessment through nuclear magnetic resonance (NMR)-based metabolomic profiling of 168 serum metabolites and had complete covariates and clinical lipid parameters, we included those without a previous diagnosis of ischemic heart disease, cerebrovascular disease, heart failure, or cardiac arrest and not on lipid-lowering medications. Relevant covariates included sociodemographic characteristics, lifestyle factors, clinical information, and fasting time. Cox regression gave adjusted hazard ratios for metabolites, including the concentrations of various lipoprotein particles, compositional profiles of different lipoproteins, ketone bodies, amino acids, fatty acids, and additional low-molecular-weight metabolic biomarkers. The least absolute shrinkage and selection operator (LASSO) regression was applied to these metabolites to screen characteristic metabolic variables. Selected feature metabolic biomarkers were added to the established model for predicting MACE risk; risk differentiation (C-statistic) and reclassification (continuous net reclassification improvement [NRI], integrated differentiation index [IDI]) were evaluated. This study included 54,561 UK Biobank participants (34,797 middle-aged adults and 19,764 elderly adults) and was followed for a median of more than 12 years. Of these, there are 1799 middle-aged individuals and 2527 elderly individuals incident of MACE (ischemic heart disease, stroke, and cardiovascular deaths). After adjusting for relevant covariates, Cox regression yielded metabolic biomarkers associated with the occurrence of MACE in the population (false discovery rate controlled P < 0.05). In the elderly, the metabolites associated with increased MACE risk were notably diminished compared to the middle-aged; and the elderly group underscored the protective function of medium and small HDL and their constituents, docosahexaenoic acid, and glycine. The more comprehensive model, which additionally includes the feature metabolic biomarkers, demonstrated enhanced discriminatory power and predictive accuracy for MACE occurrence among middle-aged individuals, evidenced by improved C-statistics (from 0.711 [95% CI 0.699-0.722] to 0.723 [0.711-0.734]), a continuous NRI of 0.247 [0.207-0.315], and an absolute IDI of 0.005 [0.004-0.008]. Its evaluation value is superior to that in the elderly. Our study explored the association of circulating metabolites with MACE risk in middle-aged and elderly adults and made comparisons. Metabolomic insights have revealed biomarkers associated with new-onset MACE in different age populations, highlighting the value of protective metabolites in the elderly. This provides instrumental information to possibly implement precision medicine for preventing MACE.

Auditory steady state response can predict declining EF in healthy elderly individuals

BackgroundThe aging population imposes significant economic and societal challenges, underscoring the need for early detection of individuals at risk of cognitive decline prior to the onset of clinical symptoms. This study explores the association between gamma-band Auditory Steady-State Responses (ASSRs) and subclinical cognitive decline using longitudinal data from healthy volunteers in the Metropolit Birth Cohort (MBC).MethodsLongitudinal recordings of cognitive test results and ASSRs at 40 Hz stimulation were analyzed. Generalized Linear Models (GLMs) were employed to determine the association between ASSR characteristics and cognitive performance with an emphasis on Executive Function (EF) at ages 61–68. Additionally, Vision Transformers (ViTs) were trained to distinguish between individuals with declining and stable cognitive performance.ResultsSubjects with declining cognitive performance through midlife showed a larger area of entrainment and delayed neural assembly of ASSRs compared to those with stable cognitive performance. These neurophysiological changes were correlated with poorer EF, as measured by the Stockings of Cambridge (SOC) task. The ViTs trained and cross-validated on time-frequency-transformed Electroencephalograms (EEGs) achieved an average cross-subject accuracy of 51.8% in identifying cognitive decline.ConclusionGamma-band ASSR characteristics are linked to early cognitive decline in middle-aged individuals, offering potential as biomarkers. However, the limited predictive accuracy of ML models emphasizes the need for further refinement to enhance their clinical applicability.

Atherogenic index of plasma and cardiovascular disease risk in cardiovascular-kidney-metabolic syndrome stage 1 to 3: a longitudinal study

BackgroundCardiovascular disease (CVD) remains a major contributor to the global disease burden. Previous studies have established a link between the atherogenic index of plasma (AIP) and CVD. However, it remains unclear whether cumulative AIP and AIP control influence the future incidence of CVD in individuals with Cardiovascular-Kidney-Metabolic (CKM) syndrome. This study aims to explore the association between cumulative AIP, AIP control levels, and the risk of CVD in individuals with CKM syndrome from stages 1 to 3.MethodsParticipants with CKM syndrome were drawn from the China Health and Retirement Longitudinal Study (CHARLS). Cumulative AIP was calculated using triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C), while AIP control levels were categorized into four groups via k-means clustering. CVD was defined by self-reported heart disease or stroke. Multivariable logistic regression and restricted cubic spline analysis were employed to examine the association between AIP and incident CVD in individuals with CKM syndrome.ResultsA total of 793 participants (18.84%) developed CVD. After adjusting for confounders, cumulative AIP were associated with the developing CVD (OR=1.139, 95% CI: 1.017-1.275, P=0.0245). Compared to group 1 (best AIP control), the OR (95% CI) for incident CVD were 1.278 (0.959-1.702) for group 2, 1.329 (1.076-1.641) for group 3, and 1.195 (0.974-1.465) for group 4. Restricted cubic spline regression indicated the relationship between cumulative AIP and CVD risk is linear (P for nonlinear = 0.3377).ConclusionsIn middle-aged and elderly individuals with CKM syndrome, higher cumulative AIP and poorer AIP control were associated with an elevated incidence of CVD. These findings suggest that enhanced assessment of the AIP index could inform targeted prevention strategies for CVD in the context of CKM syndrome.

Systematic Review on Heart Rate Variability (HRV) among Prediabetics Aged 45-60 Years

Heart Rate Variability (HRV) is an established non-invasive marker used to assess autonomic nervous system (ANS) function. Recent studies have highlighted the potential role of HRV as an early indicator of metabolic dysfunction in prediabetes, particularly for middle-aged individuals. The early age detection will help in early treatment and prevention of dysautonomia like neuropathy, retinopathy. Early diagnosis of dysautonomia can potentially lead to a better prognosis and quality of life. This systematic review aims to highlight the current researches on HRV in prediabetic populations aged 45–60 years, exploring the relationship between reduced HRV and early cardiovascular autonomic dysfunction. Studies employing traditional HRV measures are used to identify the predictive value of HRV in prediabetes and the progression to Type 2 Diabetes Mellitus (T2DM) in middle aged individuals using PRISMA guidelines with two independent reviewers assessing the quality of included studies. The studies have shown a high corelation between heart rate variability (HRV) and prediabetes among individuals aged 45-60 years (middle aged).HRV could be used as a predictor of dysautonomia in prediabetic individuals for progression of diabetes (T2DM)

Association of a novel nutritional index with cognitive impairment in middle-aged and elderly Chinese adults: a cross-sectional analysis from the China Health and Retirement Longitudinal Study

PurposeThe triglyceride-cholesterol-body weight index (TCBI), a novel and easily computable nutritional index, incorporates serum triglyceride (TG), total cholesterol (TC), and body weight (BW). This study explored the association between TCBI and cognitive impairment in middle-aged and elderly Chinese populations.Patients and methodsThis cross-sectional study employed data from the China Health and Retirement Longitudinal Study (CHARLS) baseline survey, including 7,145 participants. TCBI was calculated as TG (mg/dL) × TC (mg/dL) × BW (kg)/1,000. Cognitive function was assessed based on mental status and episodic memory, with a total score below 11 indicating cognitive impairment. The relationship between TCBI and cognitive impairment was examined using multiple logistic regression, smooth curve fitting, and subgroup analyses.ResultsAfter full adjustment, each 1-unit increase in log-transformed TCBI (Lg TCBI) was associated with a 29.7% reduction in cognitive impairment risk [odds ratio (OR) = 0.703, 95% confidence interval (CI): 0.529–0.933; p = 0.015]. When Lg TCBI was categorized into quartiles, the Q2, Q3, and Q4 groups exhibited a reduced risk of cognitive impairment by 19.9, 16.3, and 22.9%, respectively (p for trend = 0.043), compared to the Q1 group. Smooth curve fitting revealed a consistent decrease in cognitive impairment risk with higher Lg TCBI levels. Subgroup analysis indicated that the association was stronger among participants aged ≥60 years (OR = 0.655, 95% CI: 0.438–0.979), non-current drinkers (OR = 0.643, 95% CI: 0.451–0.917), and those who engaged in socializing (OR = 0.568, 95% CI: 0.371–0.871).ConclusionTCBI was significantly and negatively associated with cognitive impairment in Chinese middle-aged and elderly individuals, with the effect more pronounced in those aged ≥60 years, non-current drinkers, and socially active participants.

Nomogram for predicting mild cognitive impairment in Chinese elder CSVD patients based on Boruta algorithm

BackgroundThe number of patients with cerebral small vessel disease is increasing, especially among the elderly population. With the continuous improvement of detection techniques, the positivity rate keeps increasing. Our goal is to develop a nomogram for early identification of PSCI and PSCID in stroke patients.MethodsIn a retrospective cohort, chained data imputation was performed to ensure no statistical differences from the original dataset. Subsequently, Boruta algorithm was utilized for variable selection based on their importance, followed by logistic regression employing backward stepwise regression. Finally, the regression results were visualized as a Nomogram.ResultsThe nomogram chart in this study achieves clinical utility in a concise and user-friendly manner, passing the Hosmer-Lemeshow goodness-of-fit test. ROC and calibration curves indicate its high discriminative ability.ConclusionWhile CSVD is prevalent among middle-aged and older individuals, cognitive decline trajectories differ. Endocrine metabolic indicators like IGF-1 offer early predictive value. This study has produced a succinct nomogram integrating demographic and clinical indicators for medical application.

Association between remnant cholesterol and depression in middle-aged and older Chinese adults: a population-based cohort study

BackgroundThe focus on remnant cholesterol (RC) has intensified because of its association with various diseases. In this study, we investigated the association between RC and depression in middle-aged and older adults.MethodsThe study involved 7,305 participants from the 2015 and 2018 waves of the China Health and Retirement Longitudinal Study. Based on the 10-item Center for Epidemiological Studies Depression Scale (CESD-10), depression was indicated by scores ≥ 12. To assess the correlation between RC levels and depression, a logistic regression model that incorporated restricted cubic spline techniques was used.ResultsOf the study population, (mean age: 60.0 ± 9.5 years), 50.3% were female. From 2015 to 2018, the mean CESD-10 score increased from 6.31 ± 3.56 to 7.85 ± 5.23. Following adjustment for confounding factors, individuals in the higher RC level quartile exhibited a higher depression risk (Q3: odds ratio [OR]: 1.75, 95% confidence intervals [CI]: 1.29–2.39; Q4: OR: 2.68, 95% CI: 1.96–3.68, P for trend &amp;lt; 0.001), with a linear correlation between RC levels and depression (P for nonlinearity = 0.108). And the subgroup analysis yielded results consistent with the primary findings.ConclusionThis study revealed that in China, in middle-aged and older individuals, elevated RC levels were associated with a higher depression risk, suggesting RC is a promising target for depression prevention and treatment.

The Insight Study: A Case-Control Psychological Autopsy Study Examining Factors Associated With Suicide in Middle-Aged People.

Despite current suicide prevention strategies, suicide rates are increasing in many Western countries in the 45-60 age group. To comprehend the high risk of suicide in this group, it is essential to gain insight into its risk factors. A case-control psychological autopsy study examined the differences between individuals who died by suicide (i.e., suicide cases) and those with psychological problems (i.e., living controls) between the ages of 45 and 60 years. Eighty-two informants were interviewed regarding 48 suicide cases and 23 controls. Controls were significantly more likely than suicide cases to have discussed the subject of euthanasia (45.5% vs.15.2%), to experience physical problems (95.7% vs. 70.8%), and to undergo treatment for these problems (73.9% vs. 39.6%). Suicide cases were more likely to be diagnosed with a depressive episode, depressive disorder (87.5% vs. 60.9%), but less likely to have current treatment for psychiatric disorders (70.8% vs. 95.7%). Suicide cases were more likely than controls to experience problems at work (85.4% vs. 60.9%), future financial problems (59.0% vs. 22.2%), and concerns about these problems (56.8% vs. 22.2). The results suggest possibilities for suicide prevention among middle-aged individuals through targeted interventions addressing mental healthcare, occupational settings, and financial distress.

The effect of lutein supplementation combined with a low-calorie diet on pro-oxidant/antioxidant balance and serum levels of adiponectin and leptin in the middle-aged obese individuals: A randomized clinical trial

The effect of lutein supplementation combined with a low-calorie diet on pro-oxidant/antioxidant balance and serum levels of adiponectin and leptin in the middle-aged obese individuals: A randomized clinical trial

Pathways to usage intention of mobile health apps among hypertensive patients: A fuzzy-set qualitative comparative analysis.

Background: The efficacy of mHealth apps in managing hypertension has been proven; however, low usage intention remains a significant challenge, warranting an in-depth exploration of the influencing factors. Objectives: This study aimed to examine the factors influencing hypertensive new users' intention to use mobile health applications through a cross-sectional survey. Methods: Fuzzy-set qualitative comparative analysis (fsQCA) was employed to investigate the combinations of various determinants, including technology acceptance, adoption factors, compliance behavior initiation factors, and time motivation factors for decision making. Results: A total of 100 middle-aged and elderly hypertensive individuals participated in the survey, with 98 responses included in the final statistical analysis. The analysis identified four distinct configurations that contribute to high usage intentions, with solution consistency and coverage values of 0.93 and 0.36, respectively. Conclusion: The findings suggest that intervention strategies should account for the various pathways leading to usage intentions.

Role Identity, Loneliness, and Bereavement During the Pandemic in Japan: A Cross-Sectional Study.

The COVID-19 pandemic significantly restricted social activities, prompting a re-examination of community dynamics. In Japan, where families are central, the absence of a spouse increases susceptibility to loneliness and isolation. The loss of a spouse, especially during the pandemic, has heightened these issues among middle-aged and older individuals. Limited quantitative studies on pandemic-related bereavement in Japan underscore the need to understand the associated risks of loneliness and social isolation. This study aimed to examine the relationships between role identity as a member of the local community, loneliness, and social support among middle-aged and older adults. This study also examined whether there were differences in the relationships between those who had experienced bereavement and those who had not. An Internet survey was conducted with Japanese adults (aged 50-74 years), including those who experienced bereavement during the pandemic. The final sample included 322 participants (154 in the bereavement group and 168 in the cohabiting group). The variables, measured using psychological scales, included role identity as a local resident, social capital (trust, reciprocity, and membership), loneliness, and social support (family and friendship). The higher trust and role identity were related to lower loneliness. Membership in the cohabiting group was related to lower level of loneliness and higher level of social supports. However, membership in the bereavement group was not related to either. Furthermore, trust and reciprocity were related to loneliness and social support. These results indicated that the role identity and perception of social capital related to preventing isolation and loneliness for bereaved people.

P-1486. Comprehensive Approach to Vibrio Vulnificus: Integrating Drug Therapy, Diagnostic Modalities, and Targeted Care for At-Risk Populations

Abstract Background Vibrio vulnificus (VV), is endemic to warm coastal waters where it causes significant foodborne and aquatic illnesses resulting in high mortality and morbidity. There are no FDA-approved treatments or standard management strategies. Here we explore the landscape of VV infections, their characteristics and treatment outcomes.Figure 1:Outcome of Vibrio Vulnificus Infections Methods Cases of VV from 2014 to 2024 were identified from PubMed and Embase databases, employing pertinent keywords, MeSH terms, and Emtree terms. Articles underwent screening using Rayyan.ai using PRISMA protocol. 72 cases that met inclusion criteria were entered to CURE ID and aggregated data was analyzed.Figure 2:Age Distribution of Vibrio Cases Results The outcome distribution of cases are in Figure 1. 46/72 patients recovered while 21 died. Age and gender of patients with VV infections are displayed in Figure 2 and 3 respectively. Most cases occurred in middle aged individuals while there was a male prevalence in cases. Figure 4 displays the countries where most infections occurred. China and the United States had the highest incidence of cases.Figure 3:Sex of Patients Conclusion The high mortality of VV underscores the importance of finding treatment options for this often-forgotten disease. The age and sex distribution in middle aged males is indicative of the correlation between aquatic activity such as fishing and VV. Males who engage in these activities are at highest risk of contracting VV infections. The geographic distribution of cases underscores countries with warm oceans is where most cases occur. In our data we noticed a prevalence of chronic liver diseases amongst VV patience. We aim to explore this correlation and most effective antimicrobials in a full manuscript.Figure 4:Geographic Distribution of Vibrio Vulnificus Disclosures All Authors: No reported disclosures

Relationship between triglyceride glucose-body mass index baselines and variation with future cardiovascular diseases risk in the middle-aged and elderly individuals

BackgroundCardiovascular diseases (CVDs) are gradually becoming the leading cause of morbidity and mortality among chronic non-communicable diseases. Previous studies have found that the TyG index is an effective alternative indicator for insulin resistance (IR) and is associated with cardiovascular events. Additionally, obesity directly or indirectly increases the risk of developing CVDs. Up to now, studies on the combined effects of these factors are insufficient, and the conclusions are not yet consistent. This study aims to analyze whether the baseline levels and fluctuations of triglyceride glucose-body mass index (TyG-BMI) are associated with the incidence of CVDs and their subtypes in a prospective cohort of middle-aged and elderly individuals.MethodsThe data for this study were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which is an ongoing nationally representative prospective cohort study. After excluding participants with partially missing variables that could affect the study results, this study ultimately included 7,072 participants, with data records spanning from 2011 to 2020. The exposures were TyG-BMI and the change in TyG-BMI from 2011 to 2015. The TyG-BMI index was calculated as TyG index multiply BMI. The change of TyG-BMI was categorized using K-means clustering and baseline TyG-BMI was grouped based on quartiles. We used Cox proportional hazards models to evaluate the relationship between baseline quartiles of the TyG-BMI index and its variability with CVDs and their subtypes.ResultsAmong the 7,072 participants (mean age of 59.1 ± 9.3 years), 3330 (47%) were male. During an average follow-up of 7.1 years, 1,774 (25.1%) participants developed new-onset cardiovascular diseases. After stratification by baseline TyG-BMI quartiles, higher TyG-BMI levels were associated with an increased risk of CVDs, The hazard ratio (HR) and 95% confidence interval (95% CI) for the highest quartile group were 1.69 (1.44-2.00). After adjusting for potential confounding factors, compared to participants with consistently low TyG-BMI levels, those with moderate TyG-BMI levels and a slowly increasing trend had an HR of 1.27 (95% CI 1.10-1.47), while those with the highest TyG-BMI levels and a slowly decreasing trend had an HR of 1.52 (95% CI 1.26-1.83).ConclusionMaterial changes in the TyG-BMI are independently associated with the risk of CVDs in middle-aged and elderly individuals. Detecting long-term changes in the TyG-BMI may aid in the early identification of high-risk individuals and help prevent the occurrence of various cardiovascular diseases.

GDF11 restores the impaired function of EPCs-MA by promoting autophagy: GDF11 ameliorates endothelial progenitor cell aging by promoting autophagy

Abstract Objective Our study aimed to assess the effects of Growth and differentiation factor 11 (GDF11) on the function of endothelial progenitor cells in middle-age individuals (EPCs-MA) isolated from mouse bone marrow and to explore the mechanistic relationship between GDF11 and age-related ALP impairment. Methods Bone marrow-derived EPCs were isolated, culture and GDF11 treatment. In vivo, the mice model of myocardial ischemia (MI) was induced by permanent ligation of the left anterior descending coronary artery (LAD) and mice were randomly divided into MI group and EPCs transplantation group (EPCs-Y, EPCs-MA, EPCs-MA/GDF11). The positive effect of GDF11 treatment of EPCs-MA on MI was verified by echocardiography and the average ratio of fibrotic area to left ventricular (LV) area. In vitro, the effect of GDF11 on ameliorating EPCs aging by promoting autophagy was confirmed by transwell assay, immunofluorescence staining, characterization of EPCs ultrastructure through transmission electron microscope (TEM), lysosome imaging and Western blot. Result Our findings demonstrate that GDF11 enhances the migration capacity of EPCs-MA and improves recovery of impaired cardiac function after myocardial infarction (MI) in mice, with EPCs isolated from young mice (EPCs-Y) as controls. Moreover, GDF11 restored functional phenotypes of EPCs-MA to levels akin to EPCs-Y, promoting the expression of CD31, endogenous NO synthase, and the restoration of von Willebrand factor (vWF) and CDH5 expression patterns, as well as the formation of Weibel-Palade bodies—key organelles for storage and secretion in endothelial cells and EPCs. Furthermore, GDF11 significantly enhanced the autophagic clearance capability of EPCs-MA by promoting ALP. Conclusions Our results suggest that GDF11 ameliorates cardiac function impairment by restoring the activities of EPCs from aging mice through enhanced ALP. These findings suggest that GDF11 may hold therapeutic potential for improving aging-related conditions associated with declined autophagy.

Social Activities and Cognitive Functioning Across Mid- and Late-Life: Evidence from China.

Social engagement is positively associated with cognitive health, yet the role of these activities across the life span and in different contexts remains under-explored. This study investigates the association between social activities and two domains of cognitive functioning among middle-aged and older Chinese individuals, a population with the highest number of dementia cases in the world. We pay particular attention to the unique role of activities in midlife on cognitive decline in the later years. Using longitudinal data from the China Health and Retirement Longitudinal Study (2011-2018), we conducted mixed-effects linear models to determine the intra- and inter- individual variation on the relationship between social activity and cognitive functioning (N = 26,622 observations nested within 8,089 individuals). Across domains (episodic memory, mental intactness, and total cognition), more social activities in a given year are associated with increased cognitive functioning, independent of age. Independent of these within-individual changes, participation in social activities in midlife predicts better cognitive function across mid and later life across all domains, controlling for childhood adversities, friendship, self-rated health. However, midlife social activities do not significantly predict a slower rate of cognitive decline. Midlife social engagement has a lasting association with cognitive health in later life, yet it is important to recognize that changes occurring throughout both midlife and later life are associated with changes in cognition. This highlights the potential for modification and improvement during this period in the lifespan for aging Chinese.

Middle-aged man with primary hyperparathyroidism-associated psychosis: A case report.

Primary hyperparathyroidism (PHPT) with mild hypercalcemia (Ca <12 mg/dL) often remains asymptomatic. However, PHPT may induce various psychiatric symptoms, including depression, cognitive dysfunction, and infrequently, psychotic symptoms, predominantly in older adults rather than in middle-aged or younger individuals. A 48-year-old man, with no history of physical or mental illness, experienced delusions about a suspicious car in his neighborhood, believing it was linked to criminal activity. This led to his being taken into custody after harming himself and his family. He was admitted for psychiatric evaluation and diagnosed with PHPT after mild hypercalcemia was discovered. He was initially treated medically for the mild hypercalcemia; however, only his disorientation showed improvement, and his broader psychiatric symptoms persisted. His delusions ceased only after surgical intervention. Following discharge, he remained symptom-free without requiring antipsychotic medication. This case highlights the importance of considering PHPT in patients of any age presenting with psychosis, even with mild hypercalcemia. Surgical options for patients with PHPT should be considered when medical interventions fail.

Association between the hemoglobin A1c/High-density lipoprotein cholesterol ratio and stroke incidence: a prospective nationwide cohort study in China

BackgroundStroke has emerged as an escalating public health challenge among middle-aged and older individuals in China, closely linked to glycolipid metabolic abnormalities. The Hemoglobin A1c/High-Density Lipoprotein Cholesterol (HbA1c/HDL-C) ratio, an integrated marker of glycolipid homeostasis, may serve as a novel predictor of stroke risk.MethodsOur investigation utilized data from the China Health and Retirement Longitudinal Study cohort (2011–2018). Stroke cases were identified based on self-reported, physician-confirmed diagnoses. Logistic regression models were established to determine the correlation between HbA1c/HDL-C and stroke prevalence (2011) as well as between cumulative mean HbA1c/HDL-C (2011–2015) and new stroke incidence (2015–2018). Additionally, smoothed curve fitting, subgroup analyses, and interaction tests were conducted to ensure the robustness of the findings.ResultsIn the cross-sectional analysis, 8,502 participants were enrolled, of whom 189 had a history of stroke. Our findings revealed a significant positive linear relationship between HbA1c/HDL-C and stroke prevalence after adjusting for covariates (OR: 1.26, 95% CI: 1.09–1.45). When HbA1c/HDL-C was categorized into tertiles, only the highest tertile (T3) showed a significant correlation with stroke prevalence compared to the lowest tertile (T1) (OR:1.71, 95% CI: 1.05–2.77). In the longitudinal analysis of 5,165 participants, 336 cases of new-onset stroke were identified over a follow-up period of 7 years. Adjusting for confounders, individuals with higher cumulative mean HbA1c/HDL-C exhibited an increased likelihood of new stroke incidence (OR: 1.14, 95% CI: 1.01–1.29). Using the T1 of cumulative mean HbA1c/HDL-C as a reference, the fully adjusted OR for stroke was 1.65 (95% CI: 1.21–2.24) in T2 and 1.54 (95% CI: 1.08–2.19) in T3. The predictive value of the HbA1c/HDL-C in stroke risk assessment have been significantly improved compared to the traditional HDL-C and HbA1c. Consistent associations were observed across most stratified subgroups.ConclusionsElevated baseline and cumulative mean HbA1c/HDL-C levels are significantly associated with an increased risk of stroke among middle-aged and older individuals in China, underscoring the potential of HbA1c/HDL-C as a clinical marker for long-term stroke risk assessment and prevention strategies.

Twelve-hour ultradian rhythmic reprogramming of gene expression in the human ovary during aging.

The 12-h ultradian rhythm plays a crucial role in metabolic homeostasis, but its role in ovarian aging has not been explored. This study investigates age-related changes in 12-h rhythmic gene expression across various human tissues, with a particular focus on the ovary. We analyzed transcriptomic data from the GTEx project to examine 12-h ultradian rhythmic gene expression across multiple peripheral human tissues, exploring sex-specific patterns and age-related reprogramming of both 12-h and 24-h rhythmic gene expression. Our findings revealed sex-dimorphic patterns in 12-h rhythmic gene expression, with females exhibiting stronger 12-h rhythms than males. Midlife (ages 40-49) was identified as a critical period for the reprogramming of both 12-h and 24-h rhythmic gene expression. The ovary was notable among other organs due to its high number of genes exhibiting 12-h rhythmic expression and a distinct pattern of rhythmic gene expression reprogramming during aging. This reprogramming involved two gene subsets: one subset adopted de novo 12-h rhythms, while another subset shifted from 24-h rhythms in younger individuals to dual 12-h and 24-h rhythms in middle-aged individuals. Both subsets were primarily associated with angiogenesis. This study is the first to report age-related reprogramming of 12-h rhythms in human tissues, with a particular focus on the amplification of 12-h rhythms in angiogenesis-related genes in the aging ovary. These findings provide novel insights into the mechanisms structured format of the abstract text underlying ovarian aging and suggest potential therapeutic strategies targeting rhythmic gene expression in the ovary.

PIK3R3 regulates differentiation and senescence of periodontal ligament stem cells and mitigates age-related alveolar bone loss by modulating FOXO1 expression.

Periodontal diseases are prevalent among middle-aged and elderly individuals. There's still no satisfactory solution for tooth loss caused by periodontal diseases. Human periodontal ligament stem cells (hPDLSCs) is a distinctive subgroup of mesenchymal stem cells, which play a crucial role in periodontal supportive tissues, but their application value hasn't been fully explored yet. As a regulatory subunit of PI3K, PIK3R3's role in stem cell regulation remains poorly comprehended. This study aims to explore the regulatory effect of PIK3R3 on differentiation and senescence of hPDLSCs and the underlying mechanism, as well as whether overexpression of PIK3R3 mitigate alveolar bone loss in aged rats. Human PDLSC lines with both PIK3R3 knockdown and overexpression are established. Osteogenic, adipogenic, chondrogenic and senescent induction are used to test the effect of PIK3R3 on senescence in vitro. Model of alveolar bone loss in aged mice is used to reveal the effect of PIK3R3 in vivo. FOXO1 siRNA is used for mechanism exploration. Knockdown of PIK3R3 inhibits the mRNA and protein expression of markers in osteogenic, adipogenic, and chondrogenic differentiation of hPDLSCs but promotes in vitro senescence of hPDLSCs, including cell proliferation, senescence markers expression, telomerase density and reactive oxygen species. Overexpression of PIK3R3 has the opposite effect. Furthermore, the result of Micro-CT and tissue section shows that overexpression of PIK3R3 in elder rats mitigates alveolar bone loss. Mechanistically, PIK3R3 regulates senescence of hPDLSCs through modulating FOXO1 expression. Expression of FOXO1 is altered when PIK3R3 is knocked down or overexpressed in senescent medium. Knockdown of FOXO1 promotes senescence of hPDLSCs and the senescence promoting effect of knocking down PIK3R3 is weakened when FOXO1 is highly expressed. These findings indicate that PIK3R3 modulates senescence of MSCs by regulating FOXO1 expression and shows promise as a therapeutic target for mitigating age-related alveolar bone loss.