1,720,981 research outputs found
Effect of amino acid supplementation on skeletal muscle during acute immobilization in hospitalized elderly subjects: possible impact on mitochondria
Full text linkObjective: Older patients are frequently subjected to prolonged hospitalization and extended bed rest, with a negative effect on physical activity and caloric intake. This results in a consistent loss of muscle mass and function, which is associated with functional decline and high mortality. Furthermore, acute muscle disuse can precipitate sarcopenia, defined as the age-dependent loss of muscle mass and function. The aim of this study was to investigate the effect of oral amino acid (AA) supplementation in acute immobilization. We also aimed to characterize the effect and mechanism of the AA mixture in a rodent model of skeletal muscle atrophy, focusing on mitochondrial function.
Methods: In the human study, hospitalized older patients (69-87) were included in the control group (n = 50) or were administered 25 g of AA mixture (n = 44) twice daily throughout 7 d of low mobility. We collected data related to length of stay as primary outcome measure. In-hospital mortality, 90-d post-discharge mortality, 90-d post-discharge rehospitalization, and falls also were considered. Moreover, variations of anthropometric measures, body composition and muscle architecture/strength, circulating interleukins, and oxidative stress markers between the beginning and the end of the supplementation period were analyzed as secondary outcomes. In the animal study, C57/Bl6 mice underwent immobilization of one hindlimb by stapling the foot exploiting normal dorsotibial flexion. Age-matched mice that never had their hindlimbs immobilized were used as controls. Sub-groups of mice subjected to the immobilization procedure were administered the AA mixture in drinking water (I+A) and were compared to a placebo group (I+P). After 10 days, muscle function was studied by both endurance running and grip strength tests. Tibialis anterior (TA) muscles were excised and used for mitochondrial isolation.
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Results: Similar values were reported between the two groups regarding age, body weight, and body mass index. Although no difference in terms of in-hospital, 90-d post-discharge, or overall mortality rate was observed between the two groups, a reduction in length of stay, 90-d post-discharge hospitalization, and falls was observed in the AA supplementation group rather than in controls. Furthermore, the AA mixture limited muscle architecture/strength impairment and circulating oxidative stress, which occurred during hospitalization-related bed rest. The latter data was associated with increased circulating levels of anti-inflammatory cytokines interleukin-4 and -10. In animals, hindlimb immobilization reduced maximal running times and distances, along with limb grip strength; however, the extent of reduction was lower in I+A than I+P mice. Immobilization resulted in TA atrophy, characterized by a reduction in both wet weight and TA/body weight ratio. Interestingly, these alterations were slightly observed in mice treated with the AA mixture. The mitochondrial yield from TA of I+P mice was lower than controls; of note, the mitochondrial yield from TA of I+A animals was similar to controls. AA mixture administration also preserved mitochondrial bioenergetics and oxidative damage in TA muscle, which was disrupted in I+P mice with respect to controls.
Conclusions: These results suggest that the AA mixture limits several alterations associated with low mobility in older hospitalized patients, such as length of stay, 90-d post-discharge hospitalization, and falls, preventing the loss of muscle function, as well as the increase of circulating interleukins and oxidative stress markers. Furthermore, this study demonstrates that the AA mixture prevents loss of muscle mass and function in skeletal muscle atrophy by protecting mitochondria. Other than providing a further link between mitochondria and proteostatic maintenance to muscle atrophy, these results encourage further research aimed at targeting mitochondria to treat sarcopenia
Hepatic Mitochondria-Gut Microbiota Interactions in Metabolism-Associated Fatty Liver Disease
No full textThe prevalence of metabolism-associated fatty liver disease (MAFLD) represents an urgent pandemic, complicated by a higher risk of morbidity and mortality as well as an increased socio-economic burden. There is growing evidence proving the impact of gut microbiota modifications on the development and progression of MAFLD through changes in metabolic pathways, modulation of the immune response, and activation of pro-inflammatory signals. Concurrently, metabolites produced by gut microbiota consisting of short chain fatty acids and bile acids contribute to the regulation of hepatic homeostasis by interacting with mitochondria. Evolving research indicates that innovative therapeutic targets for MAFLD may focus on gut microbiota–mitochondria interplay to regulate hepatic homeostasis. Recent investigations have explored the potential of new treatment strategies, such as prebiotics, probiotics, and metabolites, to change the composition of gut microbiota and simultaneously exert a positive impact on mitochondrial function to improve MAFLD. This review summarizes the significance of mitochondria and reports modifications in the composition of gut microbiota and its metabolites in MAFLD in order to illustrate the fascinating interplay between liver mitochondria and intestinal microbiota, discussing the potential effects of innovative treatments to modulate gut microbiota
Muscle Delivery of Mitochondria-Targeted Drugs for the Treatment of Sarcopenia: Rationale and Perspectives
No full textAn impairment in mitochondrial homeostasis plays a crucial role in the process of aging and contributes to the incidence of age-related diseases, including sarcopenia, which is defined as an age-dependent loss of muscle mass and strength. Mitochondrial dysfunction exerts a negative impact on several cellular activities, including bioenergetics, metabolism, and apoptosis. In sarcopenia, mitochondria homeostasis is disrupted because of reduced oxidative phosphorylation and ATP generation, the enhanced production of reactive species, and impaired antioxidant defense. This review re-establishes the most recent evidence on mitochondrial defects that are thought to be relevant in the pathogenesis of sarcopenia and that may represent promising therapeutic targets for its prevention/treatment. Furthermore, we describe mechanisms of action and translational potential of promising mitochondria-targeted drug delivery systems, including molecules able to boost the metabolism and bioenergetics, counteract apoptosis, antioxidants to scavenge reactive species and decrease oxidative stress, and target mitophagy. Even though these mitochondria-delivered strategies demonstrate to be promising in preclinical models, their use needs to be promoted for clinical studies. Therefore, there is a compelling demand to further understand the mechanisms modulating mitochondrial homeostasis, to characterize powerful compounds that target muscle mitochondria to prevent sarcopenia in aged people
Controlling Nutritional Status (CONUT) Score as a Predictive Marker in Hospitalized Frail Elderly Patients
No full text: The Controlling Nutritional Status (CONUT) score is a simple screening tool able to detect altered nutritional status as well as to predict clinical adverse outcomes in specific populations. No data are available in frail patients. This study aims to investigate the predictive role of the CONUT score on mortality and length of stay (LOS) in frail patients admitted to an Internal Medicine Department. We consecutively enrolled 246 patients aged 65 years or older, divided into two groups based on frailty status. The two groups were further divided according to low (<5) or high (≥5) CONUT score. Length of stay (LOS) was higher in frail patients than not-frail patients, as well as in the frail group with high CONUT scores compared to the frail group with low CONUT scores. Multiple linear regression showed an increase of 2.1 days for each additional point to the CONUT score. In-hospital mortality was higher in frail compared to not-frail patients, but it did not differ between frail patients with high CONUT scores and frail patients with low CONUT scores. An analysis of the survival curve for 30-day mortality showed a higher mortality rate for frail/high-CONUT-score patients as compared to the not-frail/low-CONUT-score group. The CONUT score shows high prognostic value for higher LOS-but not mortality-in the clinical setting of internal medicine departments for old frail patients
Prognostic Nutritional Index and Instant Nutritional Assessement Are Associated with Clinical Outcomes in a Geriatric Cohort of Acutely Inpatients
No full textBackground: Among elderly inpatients, malnutrition is one of the most important predictive factors affecting length of stay (LOS), mortality, and risk of re-hospitalization. Methods: We conducted an observational, retrospective study on a cohort of 2206 acutely inpatients. Serum albumin and lymphocytes were evaluated. Instant Nutritional Assessment (INA) and the Prognostic Nutritional Index (PNI) were calculated to predict in-hospital mortality, LOS, and risk of rehospitalization. Results: An inverse relationship between LOS, serum albumin, and PNI were found. Deceased patients had lower albumin levels, lower PNI values, and third- and fourth-degree INA scores. An accurate predictor of mortality was PNI (AUC = 0.785) after ROC curve analysis; both lower PNI values (HR = 3.56) and third- and fourth-degree INA scores (HR = 3.12) could be independent risk factors for mortality during hospitalization after Cox regression analysis. Moreover, among 309 subjects with a lower PNI value or third- and fourth-class INA, hospitalization was re-hospitalization. Conclusions: PNI and INA are two simple and quick-to-calculate tools that can help in classifying the condition of hospitalized elderly patients also based on their nutritional status, or in assessing their mortality risk. A poor nutritional status at the time of discharge may represent an important risk factor for rehospitalization in the following thirty days. This study confirms the importance of evaluating nutritional status at the time of hospitalization, especially in older patients. This study also confirms the importance for adequate training of doctors and nurses regarding the importance of maintaining a good nutritional status as an integral part of the therapeutic process of hospitalization in acute departments
C-Reactive Protein to Albumin Ratio Predicts Early Mortality in Hospitalized Older Patients, Independent of the Admission Diagnosis
No full textBackground: Malnutrition and systemic inflammation are prevalent among older hospitalized patients and are associated with increased morbidity and mortality. The C-reactive protein to albumin (CRP/Alb) ratio reflects inflammatory and nutritional status and may serve as a useful prognostic biomarker. Objective: To evaluate the prognostic value of the CRP/Alb ratio in predicting early in-hospital mortality in a large cohort of elderly patients, independent of the admission diagnosis. Methods: This retrospective observational study examined the clinical data and serum values of serum C-reactive protein (CRP), albumin, and the CRP/Alb ratio, detected at the time of admission, in a cohort of 2780 patients over sixty-five admitted to the Internal Medicine and Aging Department of the “Policlinico Riuniti” University Hospital Trust in Foggia, between 2019 and 2024. The predictive power of the CRP/Alb ratio for 7- and 30-day hospital mortality was evaluated by ROC curve analysis, Cox regression, and Kaplan–Meier survival analysis. Results: In total, 444 patients died (16%) during their in-hospital stay. The CRP/Alb ratio was significantly higher among deceased subjects (p < 0.001) than in non-deceased patients. The CRP/Alb ratio was strongly associated with mortality, particularly during the first 7 days from admission (AUC = 0.888). A CRP/Alb ratio >8 was an independent and significant predictor of mortality within 30 days (HR = 3.82, 95% CI: 2.91–5.01), but particularly within the first 7 days from hospitalization (HR = 10.17, 95% CI: 6.05–17.08). Similar results were observed among re-hospitalized patients. Conclusions: The CRP/Alb ratio is a significant and independent predictor of early in-hospital mortality in elderly patients, regardless of admission diagnosis. A threshold value >8 identifies individuals at high risk, particularly within the first week of hospitalization. This simple, cost-effective biomarker may support early risk stratification and guide targeted interventions in geriatric care
The Mediterranean Diet Slows Down the Progression of Aging and Helps to Prevent the Onset of Frailty: A Narrative Review
No full textThe aging population is rapidly increasing all over the world. This results in significant implications for the planning and provision of health and social care. Aging is physiologically characterized by a decrease in lean mass, bone mineral density and, to a lesser extent, fat mass. The onset of sarcopenia leads to weakness and a further decrease in physical activity. An insufficient protein intake, which we often observe in patients of advanced age, certainly accelerates the progression of sarcopenia. In addition, many other factors (e.g., insulin resistance, impaired protein digestion and absorption of amino acids) reduce the stimulation of muscle protein synthesis in the elderly, even if the protein intake is adequate. Inadequate intake of foods can also cause micronutrient deficiencies that contribute to the development of frailty. We know that a healthy eating style in middle age predisposes to so-called “healthy and successful” aging, which is the condition of the absence of serious chronic diseases or of an important decline in cognitive or physical functions, or mental health. The Mediterranean diet is recognized to be a “healthy food” dietary pattern; high adherence to this dietary pattern is associated with a lower incidence of chronic diseases and lower physical impairment in old age. The aim of our review was to analyze observational studies (cohort and case–control studies) that investigated the effects of following a healthy diet, and especially the effect of adherence to a Mediterranean diet (MD), on the progression of aging and on onset of frailty
Cardioprotective Effects of Resveratrol in the Mediterranean Diet: A Short Narrative Review
No full textThe beneficial effects of a Mediterranean diet are due to the numerous active compounds in the food and, particularly, the high concentration of compounds with synergistically acting antioxidant properties. Resveratrol, a stilbenoid nonflavonoid phenol, is an antioxidant that is naturally produced by numerous plants as a defensive agent in response to attacks from pathogens, such as bacteria and fungi. Resveratrol has several effects on human health, including on the lipid profile, where it primarily downregulates the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase, reducing the synthesis of cholesterol. Resveratrol also increases the expression of LDL receptors in the liver, contributing to the reduction in the LDL-cholesterol levels. This short narrative review, based on relevant articles written in English from a PubMed search, using the keywords “resveratrol”, “atherosclerosis”, “cardiovascular disease”, and “Mediterranean Diet“, focuses on the possible effects of this molecule on cardiovascular disease, lipid metabolism, and atherosclerosis
Impact of sodium glucose cotransporter-2 inhibitors on liver steatosis/fibrosis/inflammation and redox balance in non-alcoholic fatty liver disease
No full textBACKGROUND: Sodium glucose cotransporter-2 inhibitors (SGLT2-I) are the most recently approved drugs for type 2 diabetes (T2D). Recent clinical trials of these compounds reported beneficial cardiovascular (CV) and renal outcomes. A major cause of vascular dysfunction and CV disease in diabetes is hyperglycemia associated with inflammation and oxidative stress. Pre-clinical studies demonstrated that SGLT2-I reduce glucotoxicity and promote anti-inflammatory effects by lowering oxidative stress. AIM: To investigate the effects of SGLT2-I on markers of oxidative stress, inflammation, liver steatosis, and fibrosis in patients of T2D with non-alcoholic fatty liver disease (NAFLD). METHODS: We referred fifty-two consecutive outpatients treated with metformin monotherapy and exhibiting poor glycemic control to our centre. We introduced the outpatients to an SGLT2-I (dapagliflozin, empagliflozin, or canagliflozin; n = 26) or a different hypoglycemic drug [other glucose-lowering drugs (OTHER), n = 26]. We evaluated circulating interleukins and serum hydroxynonenal (HNE)- or malondialdehyde (MDA)-protein adducts, fatty liver index (FLI), NAFLD fibrosis score, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST-to-platelet-ratio index (APRI), and fibrosis-4 on the day before (T0) and following treatment for six months (T1). We also performed transient elastography at T0 and T1. RESULTS: Add-on therapy resulted in improved glycemic control and reduced fasting blood glucose in both groups. Of note, following treatment for six months, a reduction of FLI and APRI, as well as of the FibroScan result, was reported in patients treated with SGLT2-I, but not in the OTHER group; furthermore, in the SGLT2-I group, we reported lower circulating levels of interleukin (IL)-1β, IL-6, tumor necrosis factor, vascular endothelial growth factor, and monocyte chemoattractant protein-1, and higher levels of IL-4 and IL-10. We did not observe any modification in circulating interleukins in the OTHER group. Finally, serum HNE- and MDA-protein adducts decreased significantly in SGLT2-I rather than OTHER patients and correlated with liver steatosis and fibrosis scores. CONCLUSION: The present data indicate that treatment with SGLT2-I in patients with T2D and NAFLD is associated with improvement of liver steatosis and fibrosis markers and circulating pro-inflammatory and redox status, more than optimizing glycemic control
Association between Controlling Nutritional Status (CONUT) Score and Body Composition, Inflammation and Frailty in Hospitalized Elderly Patients (Q1 WoS)
No full textUnlabelled: The Controlling Nutritional Status (CONUT) score has demonstrated its ability to identify patients with poor nutritional status and predict various clinical outcomes. Our objective was to assess the association between the CONUT score, inflammatory status, and body composition, as well as its ability to identify patients at risk of frailty in hospitalized elderly patients. Methods: a total of 361 patients were retrospectively recruited and divided into three groups based on the CONUT score. Results: patients with a score ≥5 exhibited significantly higher levels of inflammatory markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Neutrophil/Lymphocytes ratio (NLR), main platelet volume (MPV), and ferritin, compared to those with a lower score. Furthermore, these patients showed unfavorable changes in body composition, including a lower percentage of skeletal muscle mass (MM) and fat-free mass (FFM) and a higher percentage of fatty mass (FM). A positive correlation was found between the CONUT score and inflammatory markers, Geriatric Depression Scale Short Form (GDS-SF), and FM. Conversely, the Mini Nutritional Assessment (MNA), Mini-Mental Status Examination, activity daily living (ADL), instrumental activity daily living (IADL), Barthel index, FFM, and MM showed a negative correlation. Frailty was highly prevalent among patients with a higher CONUT score. The receiver operating characteristic (ROC) curve demonstrated high accuracy in identifying frail patients (sensitivity). Conclusions: a high CONUT score is associated with a pro-inflammatory status as well as with unfavorable body composition. Additionally, it is a good tool to identify frailty among hospitalized elderly patients
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