Association of serum levels of phenylalanine and tyrosine with hip fractures and frailty in older adults: The cardiovascular health study.

This study examined if the amino acids phenylalanine or tyrosine contribute to risk of hip fracture or frailty in older adults. We determined that neither phenylalanine nor tyrosine are important predictors of hip fracture or frailty. We suggest advice on protein intake for skeletal health consider specific amino acid composition. PURPOSE: Protein is essential for skeletal health, but the specific amino acid compositions of protein may have differential associations with fracture risk. The aim of this study was to determine the association of serum levels of the aromatic amino acids phenylalanine and tyrosine with risk for incident hip fractures over twelve years of follow-up and cross sectional associations with frailty. METHODS: We included 131 older men and women from the Cardiovascular Health Study (CHS) who sustained a hip fracture over twelve years of follow-up and 131 men and women without an incident hip fracture over this same period of time. 42% of this cohort were men and 95% were Caucasian. Weighted multivariable Cox hazards molecules were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of incident hip fracture associated with a one standard deviation (SD) higher serum level of phenylalanine or tyrosine. Relative risk regression was used to determine the cross-sectional association of these amino acids with Freid's frailty index. RESULTS: Neither serum levels of phenylalanine (HR 0.85 (95% CI 0.62-1.16) or tyrosine (HR 0.82 (95% CI 0.62-1.1) were significantly associated with incident hip fractures or cross sectionally with frailty (frail compared with prefrail/not frail) (HR 0.92 (95% CI 0.48-1.76) and HR (0.86 (95% CI 0.46-1.61) respectively. CONCLUSION: Phenylalanine and tyrosine are not significant contributors to hip fractures or frailty in older men and women.

Association of the triglyceride-glucose index and its related parameters with frailty.

BACKGROUND: Frailty is a dynamic geriatric condition. Limited studies have examined the association of the triglyceride-glucose (TyG) index and its related indicators [TyG index, triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC), and triglyceride glucose-body mass index (TyG-BMI)] with frailty, and the potential links among them remain unclear. On the basis of data from the National Health and Nutrition Examination Survey (NHANES), this study investigated the potential relationships of the TyG index and its related indices with frailty. METHODS: This research included 7,965 participants from NHANES 2003-2018. The relationship of the TyG index and its related indices with frailty was investigated with binary logistic regression analyses, restricted cubic spline (RCS), and receiver operating characteristic (ROC) curve. Potential influences were further investigated through stratified analyses and interaction tests. RESULTS: The prevalence of frailty in the participants of this study was 25.59%, with a average frailty index of 0.16 (0.00). In the three regression analysis models, the continuous TyG index and its associated indices were positively associated with frailty. In addition, quartiles of TyG, TyG-WC, TyG-WHtR, and TyG-BMI were significantly associated with increased frailty prevalence in the fully adjusted models (TyG Q4 vs. Q1, OR = 1.58, 95% CI: 1.19, 2.09, P = 0.002; TyG-WC Q4 vs. Q1, OR = 2.40, 95% CI: 1.90, 3.04, P < 0.001; TyG-WHtR Q4 vs. Q1, OR = 2.26, 95% CI: 1.82, 2.81, P < 0.001; TyG- BMI Q4 vs. Q1, OR = 2.16, 95% CI: 1.76, 2.64, P < 0.001). According to RCS analysis, TyG, TyG-WC, TyG-WHtR, and TyG-BMI were linearly and positively associated with frailty. ROC curves revealed that TyG-WHtR (AUC: 0.654) had greater diagnostic value for frailty than TyG (AUC: 0.604), TyG-BMI (AUC: 0.621), and TyG-WC (AUC: 0.629). All of the stratified analyses and interaction tests showed similar results. CONCLUSIONS: Elevated TyG and its associaed indices are associated with an increased prevalence of frailty. Reasonable control of blood glucose and blood lipids, and avoidance of obesity, may aid in reducing the occurrence of frailty in middle-aged and older adults.

The associations between nutritional status and physical frailty and Alzheimer's disease plasma biomarkers in older cognitively unimpaired adults with positive of amyloid-ß PET.

BACKGROUND & AIMS: It has been revealed good nutritional status and no physical frailty, which are modifiable lifestyle factors, are linked to less cognitive decline and a lower risk of Alzheimer's disease (AD). We aimed to investigate the associations between nutritional status and physical frailty and plasma AD biomarkers, especially the Tau-associated biomarkers in older cognitively unimpaired (CU) adults with higher ß-amyloid (Aß) burden. METHODS: The nutritional status and physical frailty were assessed via Mini-Nutritional Assessment Short-Form (MNA-SF) and Fried frailty index. The participants underwent the examination of plasma AD biomarkers and 18F-florbetapir PET scan as well as 18F-MK6240 PET in the validation cohort. Correlation and multiple linear regression analyses were used to investigate the associations between nutritional status and frailty and AD biomarkers. RESULTS: Two cohorts were included in our study. A total of 129 participants with Aß-PET positive were enrolled in the development cohort. Multiple linear regression analysis showed MNA-SF scores, normal nutritional status, Fried frailty index scores, frailty and some domains of frailty including weight loss, maximal grip strength and exhaustion were associated with plasma p-Tau-181. Furthermore, weight loss, Fried frailty index scores and frailty were associated with higher Aß-PET standard uptake value ratio. We further performed subgroup analyses stratified by age, sex and apolipoprotein E ε4 genotype to investigate the beneficial characteristics of nutrition and frailty in the special subgroups. Validation cohort contained 38 Aß-PET positive participants. MNA-SF scores, normal nutritional status, Fried frailty index scores and frailty were associated with Tau burden evaluated by 18F-MK6240 PET Braak-like stages. CONCLUSIONS: Our data indicates that normal nutritional status and no physical frailty may be associated with expected trend of plasma AD biomarkers, especially less Tau pathology in older CU adults with Aß deposition. Adjusting to these characteristics of nutrition and physical frailty may help reduce the risk of AD development.

The Association between Circulating Cytokines and Body Composition in Frail Patients with Cardiovascular Disease.

The burden of cardiovascular disease and the percentage of frail patients in the aging population will increase. This study aims to assess the circulating levels of several cytokines in frail patients. This is an ancillary analysis of the FRAPICA trial. The ratio of men/women changed from robust through frail groups from 3:1 to 1:2. The groups are comparable in terms of age and body measurements analysis (weight, height, and BMI), yet the frail patients have significantly reduced fat-free mass, and more often have been diagnosed with diabetes. Frail patients have higher fibroblast growth factor basic (FGF basic) and follistatin levels (borderline significance). In multiple linear regression modeling of fat-free mass, we identified FGF basic, osteopontin, stem cell factor, soluble suppression of tumorigenicity 2, soluble epidermal growth factor receptor, soluble human epidermal growth factor receptor 2, follistatin, prolactin, soluble interleukin 6 receptor alfa, platelet endothelial cell adhesion molecule 1, soluble vascular endothelial cell growth factor receptor 1, leptin, soluble angiopoietin/tyrosine kinase 2, and granulocyte colony-stimulating factor. We have identified a few cytokines that correlate with fat-free mass, a hallmark of frailty. They comprise the kinins implicated in bone and muscle metabolism, fibrosis, vascular wall function, inflammation, endocrine function, or regulation of bone marrow integrity.

Higher blood biochemistry-based biological age developed by advanced deep learning techniques is associated with frailty in geriatric rehabilitation inpatients: RESORT.

BACKGROUND: Accelerated biological ageing is a major underlying mechanism of frailty development. This study aimed to investigate if the biological age measured by a blood biochemistry-based ageing clock is associated with frailty in geriatric rehabilitation inpatients. METHODS: Within the REStORing health of acutely unwell adulTs (RESORT) cohort, patients' biological age was measured by an ageing clock based on completed data of 30 routine blood test variables measured at rehabilitation admission. The delta of biological age minus chronological age (years) was calculated. Ordinal logistic regression and multinomial logistic regression were performed to evaluate the association of the delta of ages with frailty assessed by the Clinical Frailty Scale. Effect modification of Cumulative Illness Rating Scale (CIRS) score was tested. RESULTS: A total of 1187 geriatric rehabilitation patients were included (median age: 83.4 years, IQR: 77.7-88.5; 57.4 % female). The biochemistry-based biological age was strongly correlated with chronological age (Spearman r = 0.883). After adjustment for age, sex and primary reasons for acute admission, higher biological age (per 1 year higher in delta of ages) was associated with more severe frailty at admission (OR: 1.053, 95 % CI:1.012-1.096) in patients who had a CIRS score of <12 not in patients with a CIRS score >12. The delta of ages was not associated with frailty change from admission to discharge. The specific frailty manifestations as cardiac, hematological, respiratory, renal, and endocrine conditions were associated with higher biological age. CONCLUSION: Higher biological age was associated with severe frailty in geriatric rehabilitation inpatients with less comorbidity burden.

Association of two novel systemic inflammatory biomarkers and frailty based on NHANES 2007-2018.

Background: Frailty is a significant concern in the field of public health. However, currently, there is a lack of widely recognized and reliable biological markers for frailty. This study aims to investigate the association between systemic inflammatory biomarkers and frailty in the older adult population in the United States. Methods: This study employed data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018 and conducted a rigorous cross-sectional analysis. We constructed weighted logistic regression models to explore the correlation between the Systemic Immune-Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and frailty in the population aged 40 to 80 years. Using restricted cubic spline (RCS), we successfully visualized the relationship between SII, SIRI, and frailty. Finally, we presented stratified analyses and interaction tests of covariates in a forest plot. Results: This study involved 11,234 participants, 45.95% male and 54.05% female, with an average age of 64.75 ± 0.13 years. After adjusting for relevant covariates, the weighted logistic regression model indicated an odds ratio (OR) and 95% confidence interval(CI) for the correlation between frailty and the natural logarithm (ln) transformed lnSII and lnSIRI as 1.38 (1.24-1.54) and 1.69 (1.53-1.88), respectively. Subsequently, we assessed different levels of lnSII and lnSIRI, finding consistent results. In the lnSII group model, the likelihood of frailty significantly increased in the fourth quartile (OR = 1.82, 95% CI: 1.55-2.12) compared to the second quartile. In the lnSIRI group model, the likelihood of frailty significantly increased in the third quartile (OR = 1.30, 95% CI: 1.10-1.53) and fourth quartile (OR = 2.29, 95% CI: 1.95-2.70) compared to the second quartile. The interaction results indicate that age and income-to-poverty ratio influence the association between lnSIRI and frailty. RCS demonstrated a nonlinear relationship between lnSII, lnSIRI, and frailty. Conclusion: The results of this cross-sectional study indicate a positive correlation between systemic inflammatory biomarkers (SII, SIRI) and frailty.

Relationship of endogenous plasma concentrations of ß-hydroxy ß-methyl butyrate (HMB) with frailty in community dwelling older adults with type-2 diabetes mellitus.

BACKGROUND: Supplementation with ß-hydroxy ß-methyl butyrate (HMB) appears to be effective in preserving muscle in older adults. However, the association between endogenously produced HMB with frailty has not been studied in people with chronic disease. OBJECTIVES: The purpose of this study is to explore whether an association exists between endogenous HMB levels and frailty status in older adults with type-2 diabetes mellitus (T2DM). METHODS: Data were taken from the Toledo Study of Healthy Ageing, a community-dwelling aged (65 years+) cohort. Frailty was assessed at baseline and at 2.99 median years according to the Frailty Phenotype (FP) standardized to our population and the Frailty Trait Scale 12 (FTS12). The associations between HMB levels and frailty were assessed using three nested multivariate logistic regressions and segmented by sex. Glucose, HMB and glucose interaction, age and body composition were used as covariables. RESULTS: 255 participants (mean age 75.3 years, 52.94% men) were included. HMB levels showed an inverse cross-sectional association with frailty, which was modified when the interaction term HMB*glucose was included, remaining significant only for FTS12 [OR (95% CI): 0.436 (0.253, 0.751), p-value 0.003]. The association between HMB endogenous levels and FTS12 appears to be independent of sex, in which the association was maintained after adjusting for the covariates. However, there appears to be threshold points for glucose levels, above which the protective effect of HMB is lost: 145.4 mg/dl adjusted by gender for the whole sample and 149.6 mg/dl and 138.9 mg/dl for men and women, respectively. Endogenous HMB levels were not found to be associated with incident frailty. CONCLUSIONS: Cross-sectional analysis revealed that endogenous HMB levels were inversely associated with frailty as assessed by the FTS12 in older people with T2DM. This association was found to be dependent on circulating fasted glucose levels.

Frailty Influences the Relationship between the Soluble Receptor for Advanced Glycation-End Products and Mortality in Older Adults with Diabetes Mellitus.

INTRODUCTION: Frailty is prevalent among older adults with diabetes mellitus. Elevated serum levels of the soluble receptor for advanced glycation-end products (sRAGE) predict mortality in frail older adults. The evidence that sRAGE is also related to higher mortality in older adults with diabetes mellitus is inconsistent. Therefore, this study explored if frailty status influences the relationship between sRAGE and mortality in older adults with this condition. METHODS: We analysed data of 391 participants with diabetes mellitus (median age, 76 years) from four European cohorts enrolled in the FRAILOMIC project. Frailty was evaluated at baseline using Fried's criteria. Serum sRAGE was determined by ELISA. Participants were stratified by frailty status (n = 280 non-frail and 111 frail). Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between sRAGE and mortality. RESULTS: During 6 years of follow-up, 98 participants died (46 non-frail and 52 frail). Non-survivors had significantly higher baseline levels of sRAGE than survivors (median [IQR]: 1,392 [962-2,043] pg/mL vs. 1,212 [963-1,514], p = 0.008). High serum sRAGE (>1,617 pg/mL) was associated with increased mortality in the whole diabetes sample after adjustment for relevant confounders (HR 2.06, 95% CI: 1.36-3.11, p < 0.001), and there was an interaction between sRAGE and frailty (p = 0.006). Accordingly, the association between sRAGE and mortality was stronger in the frail group compared to the non-frail group (HR 2.52, 95% CI: 1.30-4.90, p = 0.006 vs. HR 1.71, 95% CI: 0.91-3.23, p = 0.099, respectively). Likewise, Kaplan-Meier curves showed a significant difference in survival rates between frail participants with high sRAGE and those with low sRAGE (p = 0.001), whereas no survival difference was seen in the non-frail group (p = 0.09). CONCLUSIONS: Frailty status influences the relationship between sRAGE and mortality in older adults with diabetes mellitus. Determination of sRAGE in this population could be a useful tool for risk stratification.

Growth Differentiation Factor 15 and Diet Quality Trajectory Interact to Determine Frailty Incidence among Middle-Aged Urban Adults.

BACKGROUND: Elevated plasma growth differentiation factor 15 (GDF15) and poor diet quality may be associated with increased frailty incidence, although their interactive associations have not been assessed in urban middle-aged adults. OBJECTIVES: We aimed to examine GDF15 and its interactive association with diet quality in relation to frailty incidence among a sample of middle-aged urban adults. METHODS: The relationship between GDF15 and diet quality trajectories in relation to incident frailty was examined in a longitudinal study of participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (2004-2017). Serum GDF15 concentration and frailty incidence were primary exposure and outcome, respectively. Group-based trajectory models were used to assess diet quality trajectories (≤3 visits/participant, N = 945, N' = 2247 observations) using the Healthy Eating Index 2010 version (HEI-2010), Dietary Inflammatory Index, and mean adequacy ratio (MAR). Cox proportional hazards models were used, testing interactive associations of GDF15 and diet quality trajectories with frail/prefrail incidence (N = 400 frailty-free at first visit, N' = 604 observations, n = 168 incident frail/prefrail). RESULTS: Both elevated GDF15 and lower diet quality trajectories were associated with a lower probability of remaining nonfrail (≤13 y follow-up). Among females, the "high diet quality" HEI-2010 trajectory had a hazard ratio (HR) of 0.15 [95% confidence interval (CI): 0.04, 0.54; P = 0.004; fully adjusted model] when compared with the "low diet quality" trajectory group. Among males only, there was an antagonistic interaction between lower HEI-2010 trajectory and elevated GDF15. Specifically, the HR for GDF15-frailty in the higher diet quality trajectory group (high/medium combined), and among males, was 2.69 (95% CI: 1.06, 6.62; P = 0.032), whereas among the lower diet quality trajectory group, the HR was 0.94 (95% CI: 0.49, 1.80; P = 0.86). Elevated GDF15 was independently associated with frailty among African American adults. CONCLUSIONS: Pending replication, we found an antagonistic interaction between GDF15 and HEI-2010 trajectory in relation to frailty incidence among males.

Association of inflammatory markers with muscle and cognitive function in early and late-aging older adults.

OBJECTIVES: Age-related loss in muscle and cognitive function is common in older adults. Numerous studies have suggested that inflammation contributes to the decline in physical performance and increased frailty in older adults. We sought to investigate the relationship of inflammatory markers, including CRP, IL-6, IL-10, TNF-α, TNFR1, and TNFR2, with muscle and cognitive function in frail early-aging and non-frail late-aging older adults. DESIGN: Secondary analysis of a cross-sectional study. SETTINGS AND PARTICIPANTS: Two hundred community-dwelling older men and women were included. They had been recruited in two groups based on age and functional status: 100 early-agers (age 65-75, who had poor functional status, and more co-morbidities) and 100 late-agers (older than 75 years, who were healthier and had better functional status). MEASUREMENTS: We assessed CRP, IL-6, IL-10, TNF-α, TNFR1, TNFR2, grip strength, Short Physical Performance Battery (SPPB) score, and cognitive function. We used correlation coefficients, partial correlations, and regression modeling adjusted for age, BMI, gender, and exercise frequency. RESULTS: The mean age in the two groups were 70.4 and 83.2, respectively. In regression models adjusting for age, BMI, gender and exercise frequency, early-agers demonstrated significant associations between inflammatory markers and outcomes. Each mg/dl of CRP was associated with (regression coefficient ± standard error) -0.6 ± 0.2 kg in grip strength (p = 0.0023). Similarly, each pg/mL of TNF-α was associated with -1.4 ± 0.7 (p = 0.0454), each 500 pg/mL of TNFR1 was associated with -1.9 ± 0.6 (p = 0.0008), and each 500 pg/mL of TNFR2 was associated with -0.5 ± 0.2 (p = 0.0098) in grip strength. Each 500 pg/mL of TNFR1 was associated with -0.4 ± 0.2 point in SPPB (p = 0.0207) and each pg/mL in IL-10 with 0.2 ± 0.1 point in MoCA (p = 0.0475). In late-agers, no significant correlation was found between any of the inflammatory markers and functional outcomes. CONCLUSION: In early-agers with frailty and more co-morbidities, the inflammatory markers CRP, TNF-α, TNFR1, and TNFR2 were associated with grip strength, TNFR1 was correlated with physical performance, and IL-10 was correlated with cognitive function. However, in healthier late-agers, no relationship was found between inflammatory markers and muscle or cognitive function. Our findings suggest presence of a relationship between inflammation and loss of muscle performance and cognitive function in frailer and sicker individuals, regardless of their chronological age.

Association between dietary inflammatory potential and frailty is mediated by inflammation among patients with colorectal cancer: A cross-sectional study.

Patients with colorectal cancer (CRC) are at high risk of frailty, leading to reduced quality of life and survival. Diet is associated with frailty in the elderly through regulating inflammation. Thus, we hypothesized that dietary inflammatory potential (as assessed by dietary inflammatory index [DII]) might be associated with frailty in patients with CRC through regulating inflammatory biomarkers. A total of 231 patients with CRC were included in this cross-sectional study. Dietary intake was evaluated by 3-day, 24-hour dietary recalls, and frailty status was assessed in accordance with the Fried frailty criteria. Plasma inflammatory cytokines were determined in 126 blood samples. A total of 67 patients (29.0%) were frail, with significantly higher DII scores than nonfrail patients, accompanied with significantly increased interleukin-6 (IL-6) and decreased interleukin-10 (IL-10) concentrations. Each 1-point increase of DII was related to a 25.0% increased risk of frailty. IL-6 was positively correlated with frailty and DII, whereas IL-10 was negatively correlated. After adjusting for age, sex, body mass index, education level, smoking status, and energy, mediation analysis revealed that the association between DII and frailty was significantly mediated by IL-6 (average causal mediation effect [ACME], 0.052; 95% confidence interval, 0.020-0.087; P = .002) and IL-10 (ACME, 0.025; 95% confidence interval, 0.004-0.063; P = .016). The ρ values for the sensitivity measure at which estimated ACMEs were zero were 0.3 and -0.2 for IL-6 and IL-10, respectively. Therefore, a pro-inflammatory diet was associated with frailty in patients with CRC possibly in part by affecting circulating IL-6 and IL-10 concentrations.

Identification of Potential Blood-Based Biomarkers for Frailty by Using an Integrative Approach.

INTRODUCTION: Although frailty is a geriatric syndrome that is associated with disability, hospitalization, and mortality, it can be reversible and preventable with the appropriate interventions. Additionally, as the current diagnostic criteria for frailty include only physical, psychological, cognitive, and social measurements, there is a need for promising blood-based molecular biomarkers to aid in the diagnosis of frailty. METHODS: To identify candidate blood-based biomarkers that can enhance current diagnosis of frailty, we conducted a comprehensive analysis of clinical data, messenger RNA-sequencing (RNA-seq), and aging-related factors using a total of 104 older adults aged 65-90 years (61 frail subjects and 43 robust subjects) in a cross-sectional case-control study. RESULTS: We identified two candidate biomarkers of frailty from the clinical data analysis, nine from the RNA-seq analysis, and six from the aging-related factors analysis. By using combinations of the candidate biomarkers and clinical information, we constructed risk prediction models. The best models used combinations that included skeletal muscle mass index measured by dual-energy X-ray absorptiometry (adjusted p = 0.026), GDF15 (adjusted p = 1.46E-03), adiponectin (adjusted p = 0.012), CXCL9 (adjusted p = 0.011), or apelin (adjusted p = 0.020) as the biomarker. These models achieved a high area under the curve of 0.95 in an independent validation cohort (95% confidence interval: 0.79-0.97). Our risk prediction models showed significantly higher areas under the curve than did models constructed using only basic clinical information (Welch's t test p < 0.001). CONCLUSION: All five biomarkers showed statistically significant correlations with components of the frailty diagnostic criteria. We discovered several potential biomarkers for the diagnosis of frailty. Further refinement may lead to their future clinical use.

Serum Growth Differentiation Factor 15 Levels Predict the Incidence of Frailty among Patients with Cardiometabolic Diseases.

INTRODUCTION: Frailty is a crucial health issue among older adults. Growth differentiation factor 15 (GDF15) is associated with inflammation, oxidative stress, insulin resistance, and mitochondrial dysfunction, which are possible pathogeneses of frailty. However, few longitudinal studies have investigated the association between GDF15 and the incidence of frailty. Therefore, we investigated whether high serum GDF15 levels are associated with the incidence of frailty. METHODS: A total of 175 older adults (mean age: 77 ± 6 years; 63% women) with cardiometabolic diseases and no frailty out of the two criteria at baseline participated. Individuals with severe renal impairment or severe cognitive impairment were excluded. Serum GDF15 levels were measured at baseline. Patients were asked to assess frailty status at baseline and annually during follow-up using the modified version of the Cardiovascular Health Study (mCHS) and the Kihon Checklist (KCL). We examined the association between GDF15 tertiles and each frailty measure during follow-up (median 38-39 months). In the multivariate Cox regression analysis, with the GDF15 tertile groups as the explanatory variables, hazard ratios (HRs) and 95% confidence intervals (CIs) for incident frailty were calculated after adjusting for covariates and using the lowest tertile group as the reference. RESULTS: During the follow-up period, 25.6% and 34.0% of patients developed frailty, as defined by the mCHS and KCL, respectively. The highest GDF15 tertile group had a significantly higher incidence of mCHS- or KCL-defined frailty than the lowest GDF15 tertile group. Multivariate Cox regression analysis revealed that the adjusted HRs for incident mCHS- and KCL-defined frailty in the highest GDF15 tertile group were 3.9 (95% CI: 1.3-12.0) and 2.7 (95% CI: 1.1-6.9), respectively. CONCLUSION: High serum GDF15 levels predicted the incidence of frailty among older adults with cardiometabolic diseases and could be an effective marker of the risk for frailty in interventions aimed at preventing frailty, such as exercise and nutrition.

Identification of novel biomarkers for frailty diagnosis via serum amino acids metabolomic analysis using UPLC-MS/MS.

PURPOSE: This study was aimed to analyze serum amino acid metabolite profiles in frailty patients, gain a better understanding of the metabolic mechanisms in frailty, and assess the diagnostic value of metabolomics-based biomarkers of frailty. EXPERIMENTAL DESIGN: This study utilized the ultra-performance liquid chromatography tandem mass spectrometry to examine amino acids associated with frailty. Additionally, we employed multivariate statistical methods, metabolomic data analysis, receiver operating characteristic (ROC) curve analysis, and pathway enrichment analysis. RESULTS: Among the assayed amino acid metabolites, we identified biomarkers for frailty. ROC curve analysis for frailty diagnosis based on the modified Fried's frailty index showed that the areas under ROC curve of tryptophan, phenylalanine, aspartic acid, and combination were 0.775, 0.679, 0.667, and 0.807, respectively. ROC curve analysis for frailty diagnosis based on Frail Scale showed that the areas under ROC curve of cystine, phenylalanine, and combination of amino acids (cystine, L-Glutamine, citrulline, tyrosine, kynurenine, phenylalanine, glutamin acid) were 0.834, 0.708, and 0.854 respectively. CONCLUSION AND CLINICAL RELEVANCE: In this study, we explored the serum amino acid metabolite profiles in frailty patients. These present metabolic analyses may provide valuable information on the potential biomarkers and the possible pathogenic mechanisms of frailty. CLINICAL SIGNIFICANCE: Frailty is a clinical syndrome, as a consequence it is challenging to identify at early course of the disease, even based on the existing frailty scales. Early diagnosis and appropriate patient management are the key to improve the survival and limit disabilities in frailty patients. Proven by the extensive laboratory and clinical studies on frailty, comprehensive analysis of metabolic levels in frail patients, identification of biomarkers and study of pathogenic pathways of metabolites contribute to the prediction and early diagnosis of frailty. In this study, we explored the serum amino acid metabolite profiles in frailty patients. These present metabolic analyses may provide valuable information on the potential biomarkers and the possible pathogenic mechanisms of frailty.

An association study of cyclase-associated protein 2 and frailty.

Frailty is a geriatric syndrome that results from multisystem impairment caused by age-associated accumulation of deficits. The frailty index is used to define the level of frailty. Several studies have searched for molecular biomarkers associated with frailty, to meet the needs for personalized care. Cyclase-associated protein 2 (CAP2) is a multifunctional actin-binding protein involved in various physiological and pathological processes, that might reflect frailty's intrinsic complexity. This study aimed to investigate the association between frailty index and circulating CAP2 concentration in 467 community-dwelling older adults (median age: 79; range: 65-92 years) from Milan, Italy. The selected robust regression model showed that circulating CAP2 concentration was not associated with chronological age, as well as sex and education. However, circulating CAP2 concentration was significantly and inversely associated with the frailty index: a 0.1-unit increase in frailty index leads to ~0.5-point mean decrease in CAP2 concentration. Furthermore, mean CAP2 concentration was significantly lower in frail participants (i.e., frailty index ≥0.25) than in non-frail participants. This study shows the association between serum CAP2 concentration and frailty status for the first time, highlighting the potential of CAP2 as a biomarker for age-associated accumulation of deficits.

Circulating miRNAs are associated with frailty and ST-elevation myocardial infarction pathways.

BACKGROUND: Frailty and ST-Elevation Myocardial Infarction (STEMI) share similar molecular pathways. Specific biomarkers, such as microRNAs (miRNAs), may provide insights into the molecular mechanisms that cause the relationship between frailty and STEMI. OBJECTIVE: Our aim was to identify and compare circulating miRNA levels between frail and non-frail older adults following STEMI and comprehend the regulatory miRNA-gene networks and pathways involved in this condition. METHODS: This exploratory study is a subanalysis of a larger observational study. In this study, we selected patients ≥ 65 years old, following STEMI, with pre-frail/frail (n=5) and non-frail (n=4) phenotype evaluated using the Clinical Frailty Scale and serum circulating miRNA levels were analyzed. RESULTS: Pre-frail/frail patients had greater serum levels of 53 miRNAs, compared with non-frail patients. Notably, miR-103a-3p, miR-598-3p, and miR-130a-3p were the top three significantly deregulated miRNAs predicted to modulate gene expression associated with aging. Additional computational analyses showed 7,420 predicted miRNA gene targets, which were regulated by at least two of the 53 identified miRNAs. Pathway enrichment analysis showed that axon guidance and MAPK signaling were among pathways regulated by miRNA target genes. CONCLUSIONS: These novel findings suggest a correlation between the identified miRNAs, target genes, and pathways in pre-frail and frail patients with myocardial infarction.

Study on the Clinical Implications of NLR and PLR for Diagnosing Frailty in Maintenance Hemodialysis Patients and Their Correlations with Patient Prognosis.

OBJECTIVE: To explore the clinical implications of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for diagnosing frailty in patients with maintenance hemodialysis (MHD) and their correlations with patient prognosis. METHODS: A total of 185 patients with MHD admitted to the hemodialysis center of our hospital were selected, 72 of whom were diagnosed with frailty according to the Chinese version of Tilburg Frailty Indicator (TFI). The relevant data were collected, and the influencing factors of frailty in MHD patients were analyzed by one-way analysis of variance (ANOVA) and multivariate logistic regression. The value of NLR and PLR in diagnosing frailty in MHD patients was observed, and patients' all-cause mortality was compared during the 3-year follow-up. The influences of different levels of NLR and PLR on the survival of MHD patients were investigated. RESULTS: Multivariate regression analysis identified that serum albumin, dialysis adequacy, NLR, and PLR are independent risk factors for frailty in MHD patients (P < 0.05). The area under the receiver operating characteristic (ROC) curve of NLR and PLR in diagnosing frailty in MHD patients was 0.859 and 0.799, respectively. Compared with the nonfrailty group, the 3-year mortality was higher, and the 3-year survival rate assessed by survival analysis was lower in the frailty group (P < 0.05). Patients with high NLR and PLR levels showed a lower 3-year survival rate. CONCLUSIONS: Dialysis adequacy, serum albumin, NLR, and PLR are independently associated with frailty in MHD patients. NLR and PLR are of a certain diagnostic value for frailty in MHD patients. MHD patients with frailty have an unfavorable prognosis, as of those with high NLR and PLR levels.

Links Between Inflammation, Mood, and Physical Function Among Older Adults With HIV.

OBJECTIVES: People living with human immunodeficiency virus (PLWH) treated with antiretrovirals have life spans similar to their HIV-negative peers. Yet, they experience elevated inflammation-related multimorbidity. Drawing on biopsychosocial determinants of health may inform interventions, but these links are understudied in older PLWH. We investigated cross-sectional relationships between psychosocial factors (mood, loneliness, and stigma), inflammatory markers, and age-related health outcomes among 143 PLWH aged 54-78 years. METHOD: Participants provided blood samples for serum cytokine and C-reactive protein (CRP) analyses, completed surveys assessing psychosocial factors and health, and completed frailty assessments. Regression models tested relationships between key psychosocial-, inflammation, and age-related health variables, adjusting for relevant sociodemographic and clinical factors. RESULTS: Participants with more depressive symptoms had higher composite cytokine levels than those with fewer depressive symptoms (ß = 0.22, t(126) = 2.71, p = .008). Those with higher cytokine levels were more likely to be prefrail or frail (adjusted odds ratio = 1.72, 95% confidence interval = 1.01-2.93) and reported worse physical function (ß = -0.23, t(129) = -2.64, p = .009) and more cognitive complaints (ß = -0.20, t(129) = -2.16, p = .03) than those with lower cytokine levels. CRP was not significantly related to these outcomes; 6-month fall history was not significantly related to inflammatory markers. DISCUSSION: Novel approaches are needed to manage comorbidities and maximize quality of life among older PLWH. Illustrating key expected biopsychosocial links, our findings highlight several factors (e.g., depressive symptoms, poorer physical function) that may share bidirectional relationships with chronic inflammation, a key factor driving morbidity. These links may be leveraged to modify factors that drive excessive health risk among older PLWH.

Sex-Specific Differences in the Effect of Free Testosterone on Sarcopenia Components in Older Adults.

Objective: The association of free testosterone (FT) with sarcopenia and its components is well known in men but incompletely understood in women. We examined the association of baseline FT with the prevalence and incidence of sarcopenia and its components in community-dwelling older adults. Design: Cross-sectional and longitudinal analysis from the prospective population-based Korean Frailty and Aging Cohort Study. Methods: A total of 1,879 community-dwelling older adults aged 70-84 years were enrolled for cross-sectional analysis and 1,583 subjects who participated in the 2-year follow-up survey were included for longitudinal analysis. Baseline FT levels was measured by radioimmunoassay. Skeletal muscle mass, handgrip strength, and physical performance tests were measured at baseline and after 2-year follow-up. Sarcopenia was defined by the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS). Results: Continuous FT levels was positively associated with the prevalence of sarcopenia in men (odds ratio [OR]=0.95; 95% confidence interval [CI]=0.89-1.00)] and women (OR=0.64, 95% CI=0.42-0.99) after adjusting for multiple confounders. In prospective analysis, low FT levels was associated with a decrease in handgrip strength in women (ß=-0.61; p=0.010) and a reduction in Timed "Up and Go" (TUG) test (ß=0.53; p=0.008) in men after 2 years. No significant correlations were found between FT levels and the incidence of sarcopenia. Conclusions: Low levels of FT may be a significant determinant of decreases in muscle strength in women and declines in physical performance in men after 2 years. Low FT do not predict loss of muscle mass in both men and women.

Association between serum lactate dehydrogenase and frailty among individuals with metabolic syndrome.

While metabolic syndrome (MetS) is associated with frailty, the correlation of serum lactate dehydrogenase (sLDH) and frailty with MetS remain uncertain. To investigate the relationship between sLDH and frail components in the US with MetS. A total of 4,066 participants aged 40-90 years were assessed from the database of the third National Health and Nutrition Examination Survey, 1988-1994. The participants were classified into MetS and non-MetS groups. Multivariate logistic regression analysis with four models were performed to assess the odds ratio (OR) of the divided tertiles of sLDH levels with frailty, and frail components including slow walking (SW), weakness, exhaustion, low physical activity (LPA), and low body weight (LBW). Higher sLDH levels were positively associated with frailty in the MetS group (p = 0.024) but not in non-MetS group (p = 0.102). After covariate adjustments, the OR of frailty in the upper two tertiles compared to the lowest tertile and revealed statistical significance (p < 0.05). Frail components of SW, weakness, exhaustion, and LPA were associated with higher sLDH (p < 0.05) except for LBW in MetS and non-MetS groups. The results demonstrated the strong association of higher sLDH levels and frailty among US individuals with MetS.