Blood espression in Frailty and Robust patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE140358 | GEO | 2020/07/31
REPOSITORIES: GEO
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Project description:This work describes for the first time a different circular RNA (circRNAs) expression pattern between frail and robust individuals. Moreover, the level of some circRNAs is modulated after a physical intervention. These results suggest that they could be used as minimally invasive biomarkers of frailty. Frailty is an intermediate and reversible geriatric syndrome that often precedes dependency. Therefore, its identification is essential to prevent dependency. Diverse molecules have been proposed as biomarkers of frailty, but none of them has reached clinical practice. Recently, circular RNAs have emerged as new non-coding RNAs. Their regulatory role together with their high stability in biofluids makes them good candidates as biomarkers for several processes, but, to date, no studies have characterized circRNA expression in frailty. We studied RNA from leukocytes of 35 frail and 35 robust individuals. After RNA-Sequencing, circRNA detection was performed by CIRI2 and Circexplorer2 and differential expression analysis by DESeq2. Validation was performed by Quantitative-PCR. A Linear Discriminant Analysis was performed to determine the best circRNA combination to discriminate frails from robusts. Besides, CircRNA candidates were studied in 13 additional elder donors before and after a 3-month physical intervention. We found 89 differentially expressed circRNAs (p-value<0.05, FC>|1.5|) with frailty. The upregulation of hsa_circ_0007817, hsa_circ_0101802 and hsa_circ_0060527 in frail individuals was validated. The combination of hsa_circ_0079284, hsa_circ_0007817 and hsa_circ_0075737 levels showed a great biomarker value with a 95.9% probability of correctly classifying frail and robust individuals. Moreover, hsa_circ_0079284 levels decreased after physical intervention in concordance with an improvement in frailty scores.
2023-01-31 | GSE206762 | GEO
Project description:Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular disease (CVD) and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Here, we studied the association of abundance (flow cytometry) and gene expression profile (RNAseq) of stem/progenitor cells (HSPCs) and molecular markers of inflammaging (ELISA) with the cardiorespiratory phenotype and prospective adverse events of individuals classified according to levels of frailty. Two cohorts of older adults were enrolled in the study. In a cohort of pre-frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (>10-fold) and peripheral blood (>200-fold) of individuals with greater physical frailty. Moreover higher frailty was associated with increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. We then studied a cohort of 104 more frail individuals (average age: 81 years) with multi-domain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1-year follow-up after adjustment for age and frailty index. In conclusion, inflammaging characterized by alarmin and pro-inflammatory cytokines in pre-frail individuals is mirrored by the pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 is upregulated within HSPCs, identifying a phenotype that associates with poor cardiovascular outcomes.
2022-03-23 | GSE190446 | GEO
Project description:Physical frailty's impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log2 HAI titers, and fold-rise in log2 HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels.
2022-02-16 | GSE196793 | GEO
Project description:Frailty is an intermediate status of human ageing process, associated with decompensated homeostasis and death. The immune phenotype of frailty and its underlying cellular and molecular processes remain poorly understood. Here we profiled 114,467 immune cells from cord blood, young adults, healthy and frail elderly using single-cell RNA and TCR V(D)J sequencing. An age-dependent accumulation of cell heterogeneity and transcriptome variability in defined immune cell types was observed. With the specific expression of gene sets, characteristic transcription factors were identified in given immune cell types of certain age group. Trajectory analysis revealed cells from non-frail and frail elderly often fall into distinct trajectories, despite similar chronological age. Numerous TCR clonotypes were shared among T cell subtypes in aged and frail samples, indicating differential pluripotency and resilience capability of aged T cells. Finally, a frailty-specific monocyte subset was identified with exclusively high expression of lncRNAs NEAT1 and MALAT1. Our results discover human frailty-specific immune cell characteristics based on the comprehensive dimensions in immune landscape of ageing and frailty.
2022-01-12 | GSE157007 | GEO
Project description:Low-grade, chronic inflammation during ageing (“inflammageing”) is suggested to be involved in the development of frailty in older age. However, studies on the association between frailty, using the frailty index definition, and inflammatory markers are limited. The aim of this study was to investigate the relationship between inflammatory markers and frailty index (FI) in older, home-dwelling adults. Home-dwelling men and women aged ≥ 70 years old, living in South-East Norway were recruited and included in a cross-sectional study. The FI used in the current study was developed according to Rockwood’s frailty index and included 38 variables, resulting in an FI score between 0 and 1 for each participant. Circulating inflammatory markers (IL-6, CRP, IGF-1, cystatin C, cathepsin S, and glycoprotein Acetyls) were analyzed from non-fasting blood samples using ELISA. Whole-genome PBMC transcriptomics was used to study the association between FI score and inflammation. The present study was a cross-sectional study that included home-dwelling men and women aged ≥ 70 years old, living in the Skedsmo area, South-East Norway. The study was conducted in 2014/2015 and has been described previously [Ottestad I, Ulven SM, Øyri LKL, Sandvei KS, Gjevestad GO, Bye A, et al. Reduced plasma concentration of branched-chain amino acids in sarcopenic older subjects: a cross-sectional study. Br J Nutr. 2018;120(4):445-53]. The participants were recruited by the National Register and received an invitation letter by mail. Briefly, a total of 2820 subjects were invited, and 437 subjects participated in the study. The participants met for a single study visit, and data was collected on dietary intake, body weight and composition, physical performance, medical history, cognitive function, risk of malnutrition, anthropometric measurements, blood pressure, heart rate, and quality of life. Non-fasting blood samples were also collected.
2023-09-01 | GSE236927 | GEO
Project description:Frailty is a geriatric multi-dimensional syndrome which reflects multisystem physiological change and is a transversal measure of reduced resilience to negative events. It is characterized by weakness, frequent falls, cognitive decline, increased hospitalization and dead, and represents a risk factor for the development of Alzheimer’s disease (AD). The fact that frailty is recognized as a reversible condition, encourages the identification of earlier biomarkers to timely predict and prevent its occurrence. SAMP8 (Senescence-Accelerated Mouse Prone-8) mice represent the most appropriate preclinical model to this aim and were used in this study to carry transcriptional and metabolic analyses in the brain and plasma respectively, upon a characterization at cognitive, motor, structural and neuropathological level at 2.5, 6 and 9 months of age. At 2.5 months SAMP8 mice started displaying memory deficits, muscle weakness and motor impairment. Functional alterations were associated with a neurodevelopment deficiency associated with reduced neuronal density and glial cell loss. Through transcriptomics we identified specific genetic signatures well distinguishing SAMP8 mice at 6 months and correlating with motor and cognitive dysfunction, whereas plasma metabolomics allowed to segregate SAMP8 mice from SAMR1 already at 2.5 months of age by detecting constitutively lower levels of acylcarnitines and lipids in SAMP8 at all ages investigated. Our findings suggest that specific genetic alterations at central level, as well as metabolomic changes in plasma, might allow to early assess a frail condition leading to dementia development, which paves the foundation for future investigation in a clinical setting.
2024-11-05 | GSE270589 | GEO
Project description:Blood espression in Frailty and Robust patients
| PRJNA589329 | ENA
Project description:Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty.
2019-09-06 | MTBLS598 | MetaboLights
Project description:As human society ages globally, age-related disorders are becoming increasingly common. Due to decreasing physiological reserves and increasing organ system dysfunction associated with age, frailty affects many elderly people, compromising their ability to cope with acute stressors. Frail elderly people commonly manifest complex clinical symptoms, including cognitive dysfunction, hypomobility, and impaired daily activity, the metabolic basis of which has been little understood. We applied untargeted, comprehensive, LC-MS metabolomic analysis to human blood from 19 frail and non-frail elderly patients, who were clinically evaluated using the Edmonton Frail Scale, the MoCA-J for cognition, and the TUG for mobility. Among 131 metabolites assayed, we identified 22 markers for frailty, cognition, and hypomobility, most of which were abundant in blood. Frailty markers included 5 of 6 markers specifically related to cognition and 6 of 12 associated with hypomobility. These overlapping sets of markers include metabolites related to antioxidation, muscle or nitrogen metabolism, and amino acids, most of which decrease in frail elderly people. Five frailty-related metabolites that decreased (1,5-anhydroglucitol, acetyl-carnosine, ophthalmic acid, leucine, and isoleucine) have been previously reported as markers of aging, providing a metabolic link between human aging and frailty. Our findings clearly indicate that metabolite profiles efficiently distinguish frailty from non-frailty. Importantly, the antioxidant, ergothioneine, which decreases in frailty, is neuroprotective. Oxidative stress resulting from diminished antioxidant levels, could be a key vulnerability for pathogenesis of frailty, exacerbating illnesses related to human aging.
2020-05-01 | MTBLS1540 | MetaboLights