Metabolic View on Human Healthspan: A Lipidome-Wide Association Study.

As ageing is a major risk factor for the development of non-communicable diseases, extending healthspan has become a medical and societal necessity. Precise lipid phenotyping that captures metabolic individuality could support healthspan extension strategies. This study applied 'omic-scale lipid profiling to characterise sex-specific age-related differences in the serum lipidome composition of healthy humans. A subset of the COmPLETE-Health study, composed of 73 young (25.2 ± 2.6 years, 43% female) and 77 aged (73.5 ± 2.3 years, 48% female) clinically healthy individuals, was investigated, using an untargeted liquid chromatography high-resolution mass spectrometry approach. Compared to their younger counterparts, aged females and males exhibited significant higher levels in 138 and 107 lipid species representing 15 and 13 distinct subclasses, respectively. Percentage of difference ranged from 5.8% to 61.7% (females) and from 5.3% to 46.0% (males), with sphingolipid and glycerophophospholipid species displaying the greatest amplitudes. Remarkably, specific sphingolipid and glycerophospholipid species, previously described as cardiometabolically favourable, were found elevated in aged individuals. Furthermore, specific ether-glycerophospholipid and lyso-glycerophosphocholine species displayed higher levels in aged females only, revealing a more favourable lipidome evolution in females. Altogether, age determined the circulating lipidome composition, while lipid species analysis revealed additional findings that were not observed at the subclass level

Investigating the circulating sphingolipidome response to a single high-intensity interval training session within healthy females and males in their twenties (SphingoHIIT): Protocol for a randomised controlled trial.

Introduction: Growing scientific evidence indicates that sphingolipids predict cardiometabolic risk, independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, it remains largely unknown if and how exercise, a simple, low-cost, and patient-empowering modality to optimise cardiometabolic health, influences sphingolipid levels. The SphingoHIIT study aims to assess the response of circulating sphingolipid species to a single session of high-intensity interval training (HIIT). Methods: This single-centre randomised controlled trial (RCT) will last 11 days per participant and aim to include 32 young and healthy individuals aged 20-29 (50% females). Participants will be randomly allocated to the HIIT (n= 16) or control groups (physical rest, n= 16). Participants will self-sample fasted dried blood spots for three consecutive days before the intervention (HIIT versus rest) to determine baseline sphingolipid levels. Dried blood spots will also be collected at five time points (2, 15, 30, 60min, and 24h) following the intervention (HIIT versus rest). To minimise the dietary influence, participants will receive a standardised diet for four days, starting 24 hours before the first dried blood sampling. For females, interventions will be timed to fall within the early follicular phase to minimise the menstrual cycle's influence on sphingolipid levels. Finally, physical activity will be monitored for the whole study duration using a wrist accelerometer. Ethics and dissemination: The Ethics Committee of Northwest and Central Switzerland approved this protocol (ID 2022-00513). Findings will be disseminated in scientific journals and meetings. Trial Registration The trial was registered on www.clinicaltrials.gov (NCT05390866, https://clinicaltrials.gov/ct2/show/NCT05390866) on May 25, 2022

How Ceramides Orchestrate Cardiometabolic Health-An Ode to Physically Active Living.

Cardiometabolic diseases (CMD) represent a growing socioeconomic burden and concern for healthcare systems worldwide. Improving patients' metabolic phenotyping in clinical practice will enable clinicians to better tailor prevention and treatment strategy to individual needs. Recently, elevated levels of specific lipid species, known as ceramides, were shown to predict cardiometabolic outcomes beyond traditional biomarkers such as cholesterol. Preliminary data showed that physical activity, a potent, low-cost, and patient-empowering means to reduce CMD-related burden, influences ceramide levels. While a single bout of physical exercise increases circulating and muscular ceramide levels, regular exercise reduces ceramide content. Additionally, several ceramide species have been reported to be negatively associated with cardiorespiratory fitness, which is a potent health marker reflecting training level. Thus, regular exercise could optimize cardiometabolic health, partly by reversing altered ceramide profiles. This short review provides an overview of ceramide metabolism and its role in cardiometabolic health and diseases, before presenting the effects of exercise on ceramides in humans

The metabolic signature of cardiorespiratory fitness: a protocol for a systematic review and meta-analysis.

A low cardiorespiratory fitness (CRF) is a strong and independent predictor of cardiometabolic, cancer and all-cause mortality. To date, the mechanisms linking CRF with reduced mortality remain largely unknown. Metabolomics, which is a powerful metabolic phenotyping technology to unravel molecular mechanisms underlying complex phenotypes, could elucidate how CRF fosters human health. This study aims at systematically reviewing and meta-analysing the literature on metabolites of any human tissue sample, which are positively or negatively associated with CRF. Studies reporting estimated CRF will not be considered. No restrictions will be placed on the metabolomics technology used to measure metabolites. PubMed, Web of Science and EMBASE will be searched for relevant articles published until the date of the last search. Two authors will independently screen full texts of selected abstracts. References and citing articles of included articles will be screened for additional relevant publications. Data regarding study population, tissue samples, analytical technique, quality control, data processing, metabolites associated to CRF, cardiopulmonary exercise test protocol and exercise exhaustion criteria will be extracted. Methodological quality will be assessed using a modified version of QUADOMICS. Narrative synthesis as well as tabular/charted presentation of the extracted data will be included. If feasible, meta-analyses will be used to investigate the associations between identified metabolites and CRF. Potential sources of heterogeneity will be explored in meta-regressions. No ethics approval is required. The results will be published in a peer-reviewed journal and as conference presentation. CRD42020214375

The Metabolic Signature of Cardiorespiratory Fitness: A Systematic Review.

Cardiorespiratory fitness (CRF) is a potent health marker, the improvement of which is associated with a reduced incidence of non-communicable diseases and all-cause mortality. Identifying metabolic signatures associated with CRF could reveal how CRF fosters human health and lead to the development of novel health-monitoring strategies. This article systematically reviewed reported associations between CRF and metabolites measured in human tissues and body fluids. PubMed, EMBASE, and Web of Science were searched from database inception to 3 June, 2021. Metabolomics studies reporting metabolites associated with CRF, measured by means of cardiopulmonary exercise test, were deemed eligible. Backward and forward citation tracking on eligible records were used to complement the results of database searching. Risk of bias at the study level was assessed using QUADOMICS. Twenty-two studies were included and 667 metabolites, measured in plasma (n = 619), serum (n = 18), skeletal muscle (n = 16), urine (n = 11), or sweat (n = 3), were identified. Lipids were the metabolites most commonly positively (n = 174) and negatively (n = 274) associated with CRF. Specific circulating glycerophospholipids (n = 85) and cholesterol esters (n = 17) were positively associated with CRF, while circulating glycerolipids (n = 152), glycerophospholipids (n = 42), acylcarnitines (n = 14), and ceramides (n = 12) were negatively associated with CRF. Interestingly, muscle acylcarnitines were positively correlated with CRF (n = 15). Cardiorespiratory fitness was associated with circulating and muscle lipidome composition. Causality of the revealed associations at the molecular species level remains to be investigated further. Finally, included studies were heterogeneous in terms of participants' characteristics and analytical and statistical approaches. CRD42020214375

Metabolic Impairment in Coronary Artery Disease: Elevated Serum Acylcarnitines Under the Spotlights.

Coronary artery disease (CAD) remains the leading cause of death worldwide. Expanding patients' metabolic phenotyping beyond clinical chemistry investigations could lead to earlier recognition of disease onset and better prevention strategies. Additionally, metabolic phenotyping, at the molecular species level, contributes to unravel the roles of metabolites in disease development. In this cross-sectional study, we investigated clinically healthy individuals (n = 116, 65% male, 70.8 ± 8.7 years) and patients with CAD (n = 54, 91% male, 67.0 ± 11.5 years) of the COmPLETE study. We applied a high-coverage quantitative liquid chromatography-mass spectrometry approach to acquire a comprehensive profile of serum acylcarnitines, free carnitine and branched-chain amino acids (BCAAs), as markers of mitochondrial health and energy homeostasis. Multivariable linear regression analyses, adjusted for confounders, were conducted to assess associations between metabolites and CAD phenotype. In total, 20 short-, medium- and long-chain acylcarnitine species, along with L-carnitine, valine and isoleucine were found to be significantly (adjusted p ≤ 0.05) and positively associated with CAD. For 17 acylcarnitine species, associations became stronger as the number of affected coronary arteries increased. This implies that circulating acylcarnitine levels reflect CAD severity and might play a role in future patients' stratification strategies. Altogether, CAD is characterized by elevated serum acylcarnitine and BCAA levels, which indicates mitochondrial imbalance between fatty acid and glucose oxidation

Mikrobielle Verminderung von Methanemissionen. Teilvorhaben 1: Entwicklung eines Biofilterverfahrens zum Abbau von Methan, Geruechen und Spurengasen bei der aktiven Deponieentgasung. Teilvorhaben 2: Entwicklung eines Biofilterverfahrens zum Abbau von Methan, Geruechen und Spurengasen bei der passiven Deponieentgasung. Teilvorhaben 3: Planung, Entwicklung und Realisation halb- und grosstechnischer Biofilteranlagen an aktiven und passiven Entgasungssystemen Abschlussbericht und Anhang

Old landfills may emit considerable amounts of methane, carbon dioxide and trace gases. However, gas flow rate and methane content are usually too low for energetic utilization or flaring of the landfill gas. Microbial degradation is considered an alternative treatment for the reduction of methane emissions from those sites. The project aimed in the investigation of the suitability of actively vented biofilters for this purpose and the collection of operational experience and dimensioning data for large scale applications of the process. Different experimental plants were operated in laboratory scale (filter volume: 60 L) and container scale (filter volume: 4 m"3). The laboratory scale plant was operated with synthetic methane, whereas the container scale plant was set up at an old landfill and operated with real landfill gas. For each plant, the gas was diluted with ambient air prior to feeding into the closed biofilters, thus sufficient oxygen for methane oxidation was present throughout the filter material. At first, fine-grained compost as biofilter material was investigated. A biofilter unit of 15 m"3 size containing porous clay pellets as filter material was integrated into the recultivation layer of a Hamburg harbour sludge landfill. The parameters of landfill gas emission as well as the abiotic parameters of biofilter operation were monitored by a high-resolution automatic data collection system and gas distribution and gas emissions via the biofilter surface measured regularly. In addition, microbiological laboratory studies and studies concerning physical questions of biofilter operations were conducted. (orig.)Published in 2 volumesSIGLEAvailable from TIB Hannover: F04B412: F04B413 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung und Forschung, Berlin (Germany); Forschungszentrum Juelich GmbH (Germany)DEGerman

Recovery of mobility function and life-space mobility after ischemic stroke : the MOBITEC-Stroke study protocol

Background: Stroke is a major cause of disability and stroke incidence increases with age. Stroke frequently results in permanent limitations of mobility, and, consequently, the need for the help of others in activities of daily living. In order to optimize rehabilitative efforts and their functional outcomes, detailed knowledge of the functional recovery process, regarding mobility, is needed. Objectives of the MOBITEC-Stroke study are: 1.) To characterize mobility, including lower extremity physical function (LEPF) and life space (the geospatial extent of all of a person's movements), and changes in mobility within the first year after stroke. 2.) To identify and characterize subgroups with different mobility trajectories. 3.) To evaluate whether changes in LEPF are associated with changes in life-space. 4.) To evaluate participants' reasons for going outdoors, transportation use, and assistance needed for outdoor movement. Methods: Patients with incident first stroke who live in their own homes (target N = 59, based on sample size calculation) will be included in this cohort study. At 3, 6, 9, and 12 months after stroke a battery of mobility tests will be performed at the study centre, including laboratory-based tests of balance and strength, and quantitative gait analysis. Life-space assessment (including 1-week GPS measurements) will be performed in participants' real life. Semantic information on visited locations (reasons for going outdoors, transportation use, assistance needed) will be collected by using interactive digital maps. Linear mixed effects models will be used to model the trajectories of mobility measures for the total sample and for predefined subgroups. As an exploratory analysis, growth mixture models (GMMs) will be used to identify relevant subgroups with different trajectories. Linear mixed effect models will be used to test whether changes in LEPF parameters are associated with changes in life-space. Participants' motivation for going outdoors, transportation use, and assistance needed for outdoor mobility will be analysed descriptively. Discussion: A comprehensive and detailed knowledge of recovery patterns will enable the planning of targeted and adaptively tailored rehabilitation measures. Information about patients' reasons for outdoor mobility will provide the opportunity to define individualized and patient-oriented rehabilitation goals.peerReviewe