177,667 research outputs found
Experimental colitis: decreased Octn2 and Atb0+ expression in rat colonocytes induces carnitine depletion that is reversible by catnitine-loaded liposomes.
No full textCarnitine transporters have recently been implicated in susceptibility to inflammatory bowel disease (IBD). Because carnitine is required for beta-oxidation, it was suggested that decreased carnitine transporters, and hence reduced carnitine uptake, could lead to impaired fatty acid oxidation in intestinal epithelial cells, and to cell injury. We investigated this issue by examining the expression of the carnitine transporters OCTN2 and ATB0+, and butyrate metabolism in colonocytes in a rat model of IBD induced by trinitrobenzene sulfonic acid (TNBS). We found that Octn2 and Atb0+ expression was decreased in inflammatory samples at translational and functional level. Butyrate oxidation, evaluated based on CO2 production and acetyl-coenzyme A synthesis, was deranged in colonocytes from TNBS-treated rats. Treatment with carnitine-loaded liposomes corrected the butyrate metabolic alterations in vitro and reduced the severity of colitis in vivo. These results suggest that carnitine depletion in colonocytes is associated with the inability of mitochondria to maintain normal butyrate beta-oxidation. Our data indicate that carnitine is a rate-limiting factor for the maintenance of physiological butyrate oxidation in colonic cells. This hypothesis could also explain the contradictory therapeutic efficacy of butyrate supplementation observed in clinical trials of IBD.-D'Argenio, G., Calvani, M., Casamassimi, A., Petillo, O., Margarucci, S., Rienzo, M., Peluso, I., Calvani, R., Ciccodicola, A., Caporaso, N., and Peluso, G. Experimental colitis: decreased Octn2 and Atb0+ expression in rat colonocytes induces carnitine depletion that is reversible by carnitine-loaded liposomes
Anorexia of Aging: Metabolic Changes and Biomarker Discovery
No full textAnna Picca,1 Riccardo Calvani,1 Hélio José Coelho-Júnior,2 Francesco Landi,1,2 Emanuele Marzetti1,2 1Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy; 2Department of Geriatrics and Orthopedics, Università Cattolica Del Sacro Cuore, Rome, ItalyCorrespondence: Riccardo Calvani, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Largo A. Gemelli 8, Rome, 00168, Italy, Tel +39-06-3015-5559, Fax +39-06-3051911, Email [email protected]: The age-associated decrease in appetite and food intake is referred to as “anorexia of aging”. Older adults with anorexia show changes in the quantity/quality of energy supplied to the organism which eventually may cause a mismatch between ingested calories and physiological energy demands. Therefore, a state of malnutrition and impaired metabolism may ensue which renders older people more vulnerable to stressors and more prone to incur negative health outcomes. These latter cover a wide range of conditions including sarcopenia, low engagement in physical activity, and more severe consequences such as disability, loss of independence, hospitalization, nursing home placement, and mortality. Malnutrition has been recognized by the European Society of Clinical Nutrition (ESPEN) among the chief risk factors for the development of frailty. Frailty refers to a state of increased vulnerability to stressors stemming from reduced physiologic reserve, and according to ESPEN, is also nutrition-based. Alike frailty, anorexia is highly prevalent among older adults, and its multifactorial nature includes metabolic changes that develop in older age and possibly underly the condition. Circulating factors, including hormones (eg, cholecystokinin, ghrelin, leptin, and inflammatory and microbial mediators of gut dysbiosis), have been proposed as biomarkers for this condition to support early identification and develop personalized nutritional interventions. Additional studies are needed to untangle the interrelationship between gut microbiota and appetite regulation in older adults operating through brain–gut crosstalk. Furthermore, the contribution of the genetic background to appetite regulation and specific nutritional needs warrants investigation. Here, we provide an overview on anorexia of aging in the context of age-related metabolic changes. A special focus is placed on candidate biomarkers that may be used to assist in the early identification of anorexia of aging and in the development of personalized nutritional counseling.Keywords: frailty, geroscience, inflammation, muscle, nutrition, sarcopeni
Un caso di uveite, trombosi cerebrale, iperomocistinemia e mutazione in eterozigoti 677CÞT per MTHFR: aumentata penetranza fenotipica?
No full textNot available
Sarcopenia in Primary Care: Screening, Diagnosis, Management
No full textDetection of sarcopenia in primary care is a first and essential step in community-dwelling older adults before implementing preventive interventions against the onset of disabling conditions. In fact, leaving this condition undiagnosed and untreated can impact on the individual’s quality of life and function, as well as on healthcare costs. This article summarizes the many instruments today available for promoting an earlier and prompter detection of sarcopenia in primary care, combining insights about its clinical management. Primary care physicians may indeed play a crucial role in the identification of individuals exposed to the risk of sarcopenia or already presenting this condition. To confirm the suspected diagnosis, several possible techniques may be advocated, but it is important that strategies are specifically calibrated to the needs, priorities and resources of the setting where the evaluation is conducted. To tackle sarcopenia, nutritional counselling and physical activity programs are today the two main interventions to be proposed. Multicomponent and personalized exercise programs can (and should) be prescribed by primary care physicians, taking advantage of validated programs ad hoc designed for this purpose (e.g., the Vivifrail protocol). It is possible that, in the next future, new pharmacological treatments may become available for tackling the skeletal muscle decline. These will probably find application in those individuals non-responding to lifestyle interventions
Molecular mechanism and pathogenesis of sarcopenia: an overview
No full text: Sarcopenia involves a progressive age-related decline of skeletal muscle mass and strength/function [...]
A Novel Multi-marker Discovery Approach Identifies New Biomarkers for Parkinson's Disease in Older Peoples: an EXosomes in PArkiNson Disease (EXPAND) Ancillary Study
No full textDopaminergic nigrostriatal denervation and widespread intracellular α‐synuclein accumulation are neuropathologic hallmarks of Parkinson’s disease (PD). A constellation of peripheral processes, including metabolic and inflammatory changes, are thought to contribute to neurodegeneration. In the present study, we sought to obtain insight into the multifaceted pathophysiology of PD through the application of a multi‐marker discovery approach. Fifty older adults aged 70+, 20 with PD and 30 age‐matched controls were enrolled as part of the EXosomes in PArkiNson Disease (EXPAND) study. A panel of 68 circulating mediators of inflammation, neurogenesis and neural plasticity, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO‐CovSel), a multi‐platform regression method developed to handle highly correlated variables organized in multi‐block datasets. The SO‐CovSel model with the best prediction ability using the smallest number of variables was built with seven biomolecules. The model allowed correct classification of 94.2 ± 3.1% participants with PD and 100% controls. The biomarker profile of older adults with PD was defined by higher circulating levels of interleukin (IL) 8, macrophage inflammatory protein (MIP)‐1β, phosphoethanolamine, and proline, and by lower concentrations of citrulline, IL9, and MIP‐1α. Our innovative approach allowed identifying and evaluating the classification performance of a set of potential biomarkers for PD in older adults. Future studies are warranted to establish whether these biomolecules could serve as valuable biomarkers for PD as well as unveil new targets for interventions. Support or Funding Information Innovative Medicine Initiative‐Joint Undertaking (IMI‐JU #115621
Protein-amino acid metabolism disarrangements: The hidden enemy of chronic age-related conditions
No full textProteins are macro-molecules crucial for cell life, which are made up of amino acids (AAs). In healthy people, protein synthesis and degradation are well balanced. However, in the presence of hypercatabolic stimulation (i.e., inflammation), protein breakdown increases as the resulting AAs are consumed for metabolic proposes. Indeed, AAs are biochemical totipotent molecules which, when deaminated, can be transformed into energy, lipids, carbohydrates, and/or biochemical intermediates of fundamental cycles, such as the Krebs' cycle. The biochemical consequence of hyper-catabolism is protein disarrangement, clinically evident with signs such as sarcopenia, hypalbuminemia, anaemia, infection, and altered fluid compartmentation, etc. Hypercatabolic protein disarrangement (HPD) is often underestimated by clinicians, despite correlating with increased mortality, hospitalization, and morbidity quite independent of the primary disease. Simple, cheap, repeatable measurements can be used to identify HPD. Therefore, identification and treatment of proteins' metabolic impairment with appropriate measurements and therapy is a clinical strategy that could improve the prognosis of patients with acute/chronic hypercatabolic inflammatory disease. Here, we describe the metabolism of protein and AAs in hypercatabolic syndrome, illustrating the clinical impact of protein disarrangement. We also illustrate simple, cheap, repeatable, and worldwide available measurements to identify these conditions. Finally, we provide scientific evidence for HPD nutritional treatment
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