OUTO study
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer, Abdominal Aortic Aneurysm
PROVIDER: 19960 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:Interventions: Prehabilitation program, optimising physical health, nutritional health, factors of frailty and haemoglobin levels
Primary outcome(s): Incidence of delirium
Study Design: Non-randomized controlled trial, Open (masking not used), Active, Other
| 20031 | ecrin-mdr-crc
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:Frailty in aging is driven by the dysregulation of multiple biological pathways. Protectin DX (PDX) is a docosahexaenoic acid (DHA)-derived molecule that alleviates many chronic inflammatory disorders, but its potential effects on frailty remain unknown. Our goal is to identify age-related impairments in metabolic systems and to evaluate the therapeutic potential of PDX on frailty, physical performance, and health parameters. A set of 22-month-old C57BL/6 male and female mice were assigned to vehicle (Old) or PDX daily gavage treatment for 8 weeks, whereas 6-monthold (Adult) mice received only vehicle. Forelimb and hindlimb strength, endurance, voluntary wheel activity and walking speed determined physical performance and were combined with a frailty index score and body weight loss to determine frailty status. Our data shows that old vehicle-treated mice from both sexes had body weight loss paralleling visceromegaly, and old females also had impaired insulin clearance as compared to the Adult group. Aging was associated with physical performance decline together with higher odds of frailty development. There was also age-driven mesangial expansion and glomerular hypertrophy as well as bone mineral density loss. All of the in vivo and in vitro impairments observed with aging co-occurred with upregulation of inflammatory pathways and Myc signaling as well as downregulation of genes related to adipogenesis and oxidative phosphorylation in liver. PDX attenuated the age-driven physical performance (strength, exhaustion, walking speed) decline, promoted robustness, prevented bone losses and partially reversed changes in hepatic expression of Myc targets and metabolic genes. In conclusion, our data provides evidence of the beneficial therapeutic effect of PDX against features of frailty in mice. Further studies are warranted to investigate the mechanisms of action and the potential for human translation.
2023-04-05 | GSE228901 | GEO
Project description:AbstractBackground: A decreased intramuscular carnitine status with aging may contribute to frailty and fatigue, but studies are often confounded by sex-heterogeneity and lack of control groups. We hypothesize that muscle carnitine deficiency is associated with (pre-)frailty, diminished physical performance and altered mitochondrial function, possibly in a sex-dependent manner. This was tested in well-matched age groups, allowing gender-specific analyses. Methods: A cross-sectional study was performed in well-matched fit (n = 15) and (pre-)frail (n = 13) old males as well as in fit (n = 15) and (pre-)frail (n = 11) old females, using young males (n = 13) and females (n = 13) as healthy controls. In the elderly, frailty was assessed according to the Fried criteria and physical performance was determined by 400-m walk test, short physical performance battery and handgrip strength. Acylcarnitine status was assessed in muscle biopsies and blood plasma using liquid chromatography-tandem mass spectrometry. Muscle mitochondrial gene expression was analyzed. Results: Intramuscular total carnitine levels and short chain acylcarnitine levels were lower in (pre-)frail old females compared to fit old females and young females, whereas no differences were observed in males. Intramuscular short chain acylcarnitine levels were associated with low physical performance in females, even after correction for muscle mass (%), whereas in males no such association was found. The decline in short chain acylcarnitine levels in (pre-)frail old females was associated with low expression of genes involved in mitochondrial energy production and mitochondrial functionality. Conclusions: In (pre-)frail old females, intramuscular total carnitine levels and short chain acylcarnitine levels are decreased and this decrease is accompanied by reduced physical performance and low expression of a wide range of genes involved in mitochondrial function.
2023-02-04 | GSE144304 | GEO
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:Sarcopenia is an age-related condition characterized by progressive decline in muscle mass, strength, and physical performance, contributing to frailty and adverse health outcomes. Despite increasing interest in molecular biomarkers, longitudinal data with external validation are limited. This study utilized high-throughput proteomic analysis to identify and validate biomarkers associated with progression of sarcopenia in prospective cohorts.
2026-03-09 | PXD072647 | Pride
Project description:Frailty is a geriatric syndrome that represents a state of vulnerability with increased risk of negative health outcomes. In the last years, independent studies attempted to identify biomarkers of frailty at biological level, but no consensus has been reached to date. In this work, we performed a transcriptomic analysis of 25 robust and frail community-dwelling individuals based on Timed Up and Go, Gait Speed and Tilburg Frailty Indicator scales. The comparison between individuals classified as frail or robust by the three tools revealed the expression of 35 transcripts associated with frailty status. These include genes linked to inflammation- and hypoxia-related pathways, immune response or microRNAs. Among them, additional analyses showed that the expression of a 3-gene pattern, increased EGR1 and reduced DDX11L1 and miR454, was able to identify frail individuals with an area under the curve (AUC) of 0.86
2020-07-31 | GSE140358 | GEO
Project description:Poor parental health can influence the development and eventual health outcomes of their offspring. Many studies have detailed the maternal role yet a father’s health requires further examination as his poor nutritional status has also been shown to have negative consequences on fetal development and impact the long-term health of his offspring. The present study examined how preimplantation embryo development was altered by sub-optimal paternal diet, with specific focus on sperm- and seminal plasma-mediated mechanisms. To address this, male mice were fed a diet to model either under (low protein diet (LPD)) or over (high fat/sugar ‘Western’ diet (WD)) nutrition, LPD or WD supplemented with methyl-donors or a control diet (CD) before mating. Embryo development was assessed using in vitro time-lapse imaging of preimplantation embryos which revealed a significant increase in embryo development rates in all experimental groups when compared to CD embryos. Further analysis of the semen revealed a significant number of differentially expressed seminal plasma proteins in all groups (LPD: 13, MD-LPD: 27, WD: 24, MD-WD: 19) when compared to control. This study highlights a role for paternal nutritional status influencing embryonic development and the maternal reproductive tract via changes to his metabolic and reproductive health. These findings demonstrate potential direct (sperm-mediated) and indirect (seminal plasma-mediated) pathways in which a father's poor diet could shape the long-term health of his offspring
2024-07-25 | PXD044980 | Pride
Project description:The importance of parental diet in relation to eventual offspring health is increasing in prominence due to the increased frequency of reproductive age adults consuming poor diets. Whilst maternal health and offspring outcome have been studied in some detail, the paternal impacts are not as well understood. A father’s poor nutritional status has been shown to have negative consequences on fetal growth and development and ultimately impact the long-term adult health of the offspring. In this study we examined sperm and seminal plasma mediated mechanisms of preimplantation embryo development alterations in response to sub-optimal paternal diets. Male mice were fed a diet to model either under (low protein diet (LPD)) or over (high fat/sugar (Western) diet (WD)) nutrition, LPD or WD supplemented with methyl-donors or a control diet before mating with age-matched control fed females. Male metabolic health was influenced by WD and MD-WD; with significant changes in serum lipids and hepatic 1-carbon metabolites. Sperm RNA sequencing revealed significant changes to mRNA profiles in all groups when compared to CD (LPD: 32, MD-LPD: 17, WD: 53, MD-WD: 35). In vitro embryo development was revealed all sub-optimal diets with and without methyl-donors increased the rate of embryo development. As embryo development can be directed by sperm and seminal plasma mediated mechanism, we also examined the proteomic profile of the seminal plasma, revealing a significant number of changes in all groups compared to control (LPD: 13, MD-LPD: 27, WD: 24, MD-WD: 19). Male diet also altered uterine gene expression examined via qPCR, specifically alterations in Cd14 and Ptgs1 were observed in response to male WD matings. Our current study shows that paternal nutritional status has the potential to influence male metabolic and reproductive factors, which can ultimately alter embryonic development and the post-mating maternal environment. This study highlights potential direct (sperm mediated) and indirect (semen mediated) pathways in which a father's poor diet could shape the long-term health of his offspring.
2024-07-18 | GSE241404 | GEO
Project description:Frailty is defined as a clinical syndrome. It reflects a decrease in physiological reserve capacities that alters the mechanisms of adaptation to stress. Its clinical expression is modulated by biological, physiological, social and environmental changes. Thus, the accumulation of declines in these multiple systems leads to vulnerability to adverse outcomes (Fried et al., 2001; Nourhashémi et al., 2001). Indeed, frailty increases the risk of disability, falls, hospitalization and death. Age is currently a major determinant of frailty but does not explain this syndrome alone. It has been estimated that the prevalence of frailty is 4% in people aged 65-69 years and increases to 26% in people aged over 85 years (Clegg et al., 2013). However, this parameter is not sufficient to understand why long-lived people can preserve their physical function even at extreme ages (Ayers et al., 2017). The characterization of frailty has therefore become a priority in order to put in place actions to reduce or delay its harmful consequences. Early diagnostic methods are needed to identify those at risk. The search for biomarkers is part of this approach. As a result, the search for biomarkers of frailty has led to the identification of several types of molecules linked to the inflammatory response (e.g. IL-6, CRP, TNF-α and homocysteine), to nutritional status (e.g. vitamin D, albumin) or even endocrine. metabolism (e.g. IGF-1 and testosterone) (Picca et al., 2022; Mailliez et al., 2020; Alvarez-Sanchez et al, 2020). The development of new analytical techniques now allows multiplexed analysis rather than an individual biomarker to characterize a biological profile of this complex and dynamic frailty syndrome (Picca et al., 2022). Proteomic analysis is the technique of choice for studying the complete protein content of a biological sample. This technique has already proven itself in the discovery of new biomarkers in age-related diseases such as Parkinson's disease (Raghunathan et al., 2022) and Alzheimer's disease (Bai et al., 2021). Several studies have already described the plasma proteomic profile of frailty (Shamsi et al., 2012; Lin et al., 2017; Landino et al., 2021; Sathyan et al., 2020; Verghese et al., 2021), highlighting the importance of biological pathways associated with frailty: immune response, coagulation pathway or lipid metabolism. On the other hand, the determination of the level of frailty of the patients thanks to a proteomic analysis could also make it possible to improve the prediction of this syndrome as well as its phenotyping. In a first work on plasma samples, Sathyan et al. constructed a frailty prediction model that was more strongly correlated with chronological age than observed clinical frailty (Sathyan et al., 2020). Cognitive impairment plays a key role in determining vulnerability to adverse outcomes (Cesari et al., 2013), leading to the proposal in 2013 of a concept and operational definition of “cognitive frailty”. (Sugimoto et al., 2022). Proteomic analysis of cerebrospinal fluid (CSF) is therefore an approach of choice for understanding brain responses to aging and frailty syndrome. Its analysis could allow the identification of new biomarkers linked to the frailty syndrome. Indeed, many of the CSF proteins are released by the various cells of the central nervous system (CNS). This biofluid thus reflects the molecular content of neuronal and glial cells. For this reason, any change in the composition of the CSF reflects the pathophysiological state of the brain (inflammation, infection, neurodegeneration...). CSF proteomics is therefore a technique of choice to comprehensively understand the cerebral pathogenic pathways linked to frailty. The PROLIPHYC cohort is composed of patients suspected of normal pressure hydrocephalus (NPH). We have previously shown that there is an association in these patients between an alteration of the biomechanical properties of the CNS and the frailty index, and that homocysteine is the only plasma macromolecule associated with these two clinical and biomechanical parameters (Vallet et al., 2020; Guillotin et al., 2022). In this new study, we sought to characterize the protein composition of CSF related to frailty by quantitative proteomic analysis. The second objective was to develop a model for predicting frailty from the abundance of CSF proteins. This model was then compared to the frailty estimated by the frailty index. Together, our results enabled us to highlight a possible link between inhibition of the expression of proteins involved in neurogenesis and the frailty index, then to propose a first proteomic profile of frailty in the CSF and a model for predicting frailty based on the biological signature of the CNS.
2024-08-10 | PXD043497 | Pride