RESUMO
Mitochondrial remodeling is crucial to meet the bioenergetic demand to support muscle contractile activity during daily tasks and muscle regeneration following injury. A set of mitochondrial quality control (MQC) processes, including mitochondrial biogenesis, dynamics, and mitophagy, are in place to maintain a well-functioning mitochondrial network and support muscle regeneration. Alterations in any of these pathways compromises mitochondrial quality and may potentially lead to impaired myogenesis, defective muscle regeneration, and ultimately loss of muscle function. Among MQC processes, mitophagy has gained special attention for its implication in the clearance of dysfunctional mitochondria via crosstalk with the endo-lysosomal system, a major cell degradative route. Along this pathway, additional opportunities for mitochondrial disposal have been identified that may also signal at the systemic level. This communication occurs via inclusion of mitochondrial components within membranous shuttles named mitochondrial-derived vesicles (MDVs). Here, we discuss MDV generation and release as a mitophagy-complementing route for the maintenance of mitochondrial homeostasis in skeletal myocytes. We also illustrate the possible role of muscle-derived MDVs in immune signaling during muscle remodeling and adaptation.
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Mitocôndrias , Músculo Esquelético , Mitocôndrias/metabolismo , Músculo Esquelético/metabolismo , Mitofagia/fisiologia , Adaptação Fisiológica , Transdução de SinaisRESUMO
Functional hypothalamic amenorrhea (FHA) is characterized by estrogen deficiency that significantly impacts metabolic, bone, cardiovascular, mental, and reproductive health. Given the importance of environmental factors such as stress and body composition, and particularly considering the importance of estrogens in regulating the gut microbiota, some changes in the intestinal microenvironment are expected when all of these factors occur simultaneously. We aimed to assess whether the gut microbiota composition is altered in FHA and to determine the potential impact of hormonal replacement therapy (HRT) on the gut microbiota. This prospective observational study included 33 patients aged 18-34 yr with FHA and 10 age-matched healthy control women. Clinical, hormonal, and metabolic evaluations were performed at baseline for the FHA group only, whereas gut microbiota profile was assessed by 16S rRNA gene amplicon sequencing for both groups. All measurements were repeated in patients with FHA after receiving HRT for 6 mo. Gut microbiota alpha diversity at baseline was significantly different between patients with FHA and healthy controls (P < 0.01). At the phylum level, the relative abundance of Fusobacteria was higher in patients with FHA after HRT (P < 0.01), as was that of Ruminococcus and Eubacterium at the genus level (P < 0.05), which correlated with a decrease in circulating proinflammatory cytokines. FHA is a multidimensional disorder that is interconnected with dysbiosis through various mechanisms, particularly involving the gut-brain axis. HRT appears to induce a favorable shift in the gut microbiota in patients with FHA, which is also associated with a reduction in the systemic inflammatory status.NEW & NOTEWORTHY Our study marks the first comprehensive analysis of gut microbiota composition in FHA and the impact of HRT on it, along with biochemical, anthropometric, and psychometric aspects. Our results indicate distinct gut microbiota composition in patients with FHA compared with healthy individuals. Importantly, HRT prompts a transition toward a more beneficial gut microbiota profile and reduced inflammation. This study validates the concept of FHA as a multifaceted disorder interlinked with dysbiosis, particularly involving the gut-brain axis.
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Microbioma Gastrointestinal , Humanos , Feminino , Amenorreia , Disbiose/metabolismo , RNA Ribossômico 16S/genética , Estrogênios/farmacologiaRESUMO
OBJECTIVE: Neurodegeneration and neuroinflammation are two intertwined mechanisms contributing to the pathophysiology of Parkinson's disease. Whether circulating biomarkers reflecting those two processes differ according to disease duration remains to be established. The present study was conducted to characterize the biomarkers individuals with PD with short (≤5 years) or long disease duration (>5 years). METHODS: We consecutively enrolled 104 patients with Parkinson's disease and evaluated them using validated clinical scales (MDS-UPDRS, Hoehn and Yahr staging, MMSE). Serum samples were assayed for the following biomarkers: neurofilament light chain (NfL), brain-derived neurotrophic factor (BDNF), interleukin (IL-) 1ß, 4, 5, 6, 10, 17, interferon-γ, and tumor necrosis factor α. RESULTS: Mean age of participants was 66.0 ± 9.6 years and 45 (34%) were women. The average disease duration was 8 ± 5 years (range 1 to 19 years). Patients with short disease duration (≤ 5 years) showed a pro-inflammatory profile, with significantly higher levels of pro-inflammatory IL-1ß and lower concentrations of IL-5, IL-10 and IL-17 (p < 0.05). NfL serum levels showed a positive correlation with disease duration and age (respectively rho = 0.248, p = 0.014 and rho = 0.559, p < 0.001) while an opposite pattern was detected for BDNF (respectively rho -0,187, p = 0.034 and rho = -0.245, p = 0.014). CONCLUSIONS: Our findings suggest that a pro-inflammatory status may be observed in PD patients in the early phases of the disease, independently from age.
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Citocinas , Doença de Parkinson , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Fator Neurotrófico Derivado do Encéfalo , Fator de Necrose Tumoral alfa , Biomarcadores , Interleucina-1betaRESUMO
PURPOSE OF REVIEW: Lactose malabsorption and intolerance are very common conditions. However, their optimal approach, including the diagnostic assessment, remains a matter of debate, especially in advanced age. In this brief review, we focused on current knowledge, concerns, and impact in clinical practice of lactose malabsorption and intolerance in elderly. RECENT FINDINGS: Older adults are at high risk of malnutrition, owing to frequent occurrence of cognitive impairment, loss of appetite, dysphagia, and poor oral health. A significant decrease in the consumption of dairy products may lead to inadequate intake of high-quality protein and minerals, with a consequent impact on muscle and bone health. Testing for lactose malabsorption may be challenging in older adults, if not useless. Instead, a detailed clinical evaluation should always be pursued to identify both lactose intolerance and all confounding factors mimicking the same clinical picture. SUMMARY: The management of lactose malabsorption and intolerance in older adults deserves a personalized approach. Because of the importance of maintaining an adequate nutritional status in this age group, efforts should be put forth to avoid excessively restrictive diets.
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Intolerância à Lactose , Desnutrição , Humanos , Intolerância à Lactose/diagnóstico , Idoso , Desnutrição/diagnóstico , Estado NutricionalRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2DM) and frailty are associated with functional decline in older population. OBJECTIVE: To explore the individual response to a multimodal intervention on functional performance. DESIGN: A cluster-randomised multicentre clinical trial. SETTING: Outpatients in hospital or primary care. SUBJECTS: 843 (77.83 years, 50.65% men) prefrail and frail individuals ≥70 years with T2DM. METHODS: Participants were allocated to usual care group (UCG) or a multicomponent intervention group (IG): 16-week progressive resistance training, seven nutritional and diabetological educational sessions and achievement of glycated haemoglobin (7-8%) and blood pressure (<150 mmHg) targets. Functional performance was assessed with the Short Physical Performance Battery (SPPB) at 1 year. We used multivariate binomial and multinomial logistic regression models to explore the effect of the IG, and adherence on the outcomes studied, in several adjusted models. RESULTS: 53.7% in the IG versus 38.0% in the UCG improved by at least 1 point in their SPPB score [OR (95% CI): 2.07 (1.43, 2.98), P value <0.001]. Age, SPPB score and number of frailty criteria met decreased the probability of improving the SPPB score. Factors associated with worsening were pertaining to IG (decreased), age, SPPB score and the number of frailty criteria (increased). An adherence ≥84% was needed to achieve benefits, reaching the peak in the probability of improving SPPB when this was ≥85% [OR(95%CI): 2.38 (1.29, 4.79), P value 0.014]. CONCLUSIONS: Factors predicting the likelihood of improvement in a multimodal programme in pre-frail and frail older adults with diabetes are age, basal SPPB score, the number of frailty criteria and adherence.
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Diabetes Mellitus Tipo 2 , Fragilidade , Masculino , Idoso , Humanos , Feminino , Idoso Fragilizado , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Fragilidade/diagnóstico , Fragilidade/terapia , Pressão Sanguínea , EscolaridadeRESUMO
BACKGROUND: Falls in older adults significantly impact overall health and healthcare costs. Intrinsic capacity (IC) reflects functional reserve and is an indicator of healthy aging. AIMS: To explore the association between IC and recent falls (≤ 90 days) in community-dwelling octogenarians from the Aging and Longevity in the Sirente geographic area (IlSIRENTE) study. METHODS: The Minimum Data Set for Home Care (MDS-HC) and supplementary questionnaires and tests were used to assess the five IC domains: locomotion, cognition, vitality, psychology, and sensory. Scores in each domain were rescaled using the percent of maximum possible score method and averaged to obtain an overall IC score (range 0-100). RESULTS: The study included 319 participants (mean age 85.5 ± 4.8 years, 67.1% women). Mean IC score was 80.5 ± 14.2. The optimal IC score cut-off for predicting the two-year risk of incident loss of at least one activity of daily living (ADL) was determined and validated in a subset of 240 individuals without ADL disability at baseline (mean age 84.7 ± 4.4 years, 67.1% women). Participants were then stratified into low (< 77.6) and high (≥ 77.6) IC categories. Those with high IC (63.9%) were younger, more often males, and had lower prevalence of recent falls, disability, multimorbidity, and polypharmacy. Logistic regression models including IC as a continuous variable revealed a significant association between higher IC and lower odds of falls. This association was significant in the unadjusted (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94-0.98, p < 0.001), age- and sex-adjusted (OR 0.96, 95% CI 0.94-0.98, p < 0.001), and fully adjusted models (OR 0.96, 95% CI 0.93-0.99, p = 0.003). When considering IC as a categorical variable, unadjusted logistic regression showed a strong association between high IC and lower odds of falls (OR 0.31, 95% CI 0.16-0.60, p < 0.001). This association remained significant in both the age- and sex-adjusted (OR 0.30, 95% CI 0.15-0.59, p < 0.001) and fully adjusted models (OR 0.33, 95% CI 0.16-0.82, p = 0.007). The locomotion domain was independently associated with falls in the unadjusted (OR 0.98, 95% CI 0.97-0.99, p < 0.001), age- and sex-adjusted (OR 0.97, 95% CI 0.96-0.99, p < 0.001), and fully adjusted model (OR 0.98, 95% CI 0.96-0.99, p < 0.001). DISCUSSION: This is the first study using an MDS-HC-derived instrument to assess IC. Individuals with higher IC were less likely to report recent falls, with locomotion being an independently associated domain. CONCLUSIONS: Lower IC is linked to increased odds of falls. Interventions to maintain and improve IC, especially the locomotion domain, may reduce fall risk in community-dwelling octogenarians.
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Acidentes por Quedas , Atividades Cotidianas , Vida Independente , Humanos , Acidentes por Quedas/estatística & dados numéricos , Feminino , Masculino , Idoso de 80 Anos ou mais , Avaliação Geriátrica/métodos , Fatores de Risco , Envelhecimento/fisiologiaRESUMO
BACKGROUND: Individuals with Down syndrome (DS) experience premature aging. Whether accelerated aging involves changes in body composition parameters and is associated with early development of sarcopenia is unclear. AIMS: To compare parameters of body composition and the prevalence of sarcopenia between adults with DS and the general population. METHODS: Body composition was assessed by whole-body dual-energy X-ray absorptiometry (DXA). Fat mass (FMI) and skeletal mass indices (SMI) were calculated as the ratio between total body fat mass and appendicular lean mass and the square of height, respectively. Fat mass distribution was assessed by the android/gynoid fat ratio (A/G). Sarcopenia was defined according to the criteria and cut-points recommended by the European Working Group on Sarcopenia in Older People 2 (EWGSOP2). Data on age- and sex-matched non-DS controls were retrieved from the 2001-2002 National Health and Nutrition Examination Survey (NHANES) population. RESULTS: Sixty-four DS adults (mean age 37.2 ± 12.0 years, 20.3% women) were enrolled and compared with age- and sex-matched NHANES participants (n = 256), in a 1:4 ratio. FMI (7.96 ± 3.18 kg/m2 vs. 8.92 ± 4.83 kg/m2, p = 0.135), SMI (7.38 ± 1.01 kg/m2 vs. 7.46 ± 2.77 kg/m2, p = 0.825) and A/G (0.98 ± 0.17 vs. 1.01 ± 0.22, p = 0.115) were not significantly different between DS and control participants. When the sample was stratified by sex, women with DS had a higher FMI compared with their NHANES controls (10.16 ± 4.35 kg/m2 vs. 8.11 ± 4.29 kg/m2, p < 0.001), while men with DS had lower A/G ratio (1.04 ± 0.16 vs. 1.11 ± 0.22, p = 0.002). Sarcopenia was more frequent in individuals with DS than in controls (35.6% vs. 19.9%, p = 0.007). This association was stronger in men 40 years and older. CONCLUSIONS: Adults with DS have a higher prevalence of sarcopenia compared with the general population. This finding suggests that DS is associated with early muscle aging and calls for the design of interventions targeting the skeletal muscle to prevent or treat sarcopenia.
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Síndrome de Down , Sarcopenia , Masculino , Humanos , Feminino , Idoso , Sarcopenia/complicações , Sarcopenia/epidemiologia , Sarcopenia/diagnóstico , Inquéritos Nutricionais , Estudos de Casos e Controles , Síndrome de Down/complicações , Índice de Massa Corporal , Composição Corporal , Absorciometria de FótonRESUMO
BACKGROUND: Declining physical performance in old age is associated with a wide range of negative health-related outcomes. However, it is unclear which physical capabilities should be prioritized to obtain prognostic information in older adults. AIMS: To examine the associations between the performance on several physical function tests and falls, disability, and death in a well-characterized sample of very old Italian adults. METHODS: This was a prospective cohort study of older adults who lived in the mountain community of the Sirente geographic area in Central Italy. Physical performance was assessed using isometric handgrip strength (IHG), walking speed (WS) at a usual and fast pace, 5-time sit-to-stand test (5STS), and sit-to-stand power measures. Appendicular skeletal muscle mass was estimated from calf circumference using a validated equation. History of falls, incident falls, and disability status according to basic Activities of Daily Living (ADLs) were recorded over two years. Survival status was obtained from the participants' general practitioners and was confirmed by the National Death Registry over 10 years from enrolment. Linear, binary, and Cox regressions were performed to evaluate the association between physical performance measures and health outcomes. RESULTS: The mean age of the 255 participants was 84.2 ± 5.1 years, and 161 (63.1%) were women. Logistic regression indicated that IHG was significantly associated with incident ADL disability, whereas specific sit-to-stand muscle power was an independent predictor of death. No significant associations were observed between physical function and falls. CONCLUSIONS: Our findings indicate selective associations between physical function tests and the occurrence of negative events in very old adults, with poor IHG predicting disability and specific sit-to-stand muscle power being longitudinally associated with death.
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Atividades Cotidianas , Força da Mão , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Força da Mão/fisiologia , Estudos Longitudinais , Estudos Prospectivos , Desempenho Físico FuncionalRESUMO
Biological aging results from an accumulation of damage in the face of reduced resilience. One major driver of aging is cell senescence, a state in which cells remain viable but lose their proliferative capacity, undergo metabolic alterations, and become resistant to apoptosis. This is accompanied by complex cellular changes that enable the development of a senescence-associated secretory phenotype (SASP). Mitochondria, organelles involved in energy provision and activities essential for regulating cell survival and death, are negatively impacted by aging. The age-associated decline in mitochondrial function is also accompanied by the development of chronic low-grade sterile inflammation. The latter shares some features and mediators with the SASP. Indeed, the unloading of damage-associated molecular patterns (DAMPs) at the extracellular level can trigger sterile inflammatory responses and mitochondria can contribute to the generation of DAMPs with pro-inflammatory properties. The extrusion of mitochondrial DNA (mtDNA) via mitochondrial outer membrane permeabilization under an apoptotic stress triggers senescence programs. Additional pathways can contribute to sterile inflammation. For instance, pyroptosis is a caspase-dependent inducer of systemic inflammation, which is also elicited by mtDNA release and contributes to aging. Herein, we overview the molecular mechanisms that may link mitochondrial dyshomeostasis, pyroptosis, sterile inflammation, and senescence and discuss how these contribute to aging and could be exploited as molecular targets for alleviating the cell damage burden and achieving healthy longevity.
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Sobrevivência Celular , Senescência Celular , Mitocôndrias , Transdução de Sinais , Humanos , Mitocôndrias/metabolismo , Animais , DNA Mitocondrial/metabolismo , DNA Mitocondrial/genética , Inflamação/metabolismo , Inflamação/patologia , Morte Celular , Apoptose , Piroptose , Envelhecimento/metabolismoRESUMO
Alterations in cellular signaling, chronic inflammation, and tissue remodeling contribute to hepatocellular carcinoma (HCC) development. The release of damage-associated molecular patterns (DAMPs) upon tissue injury and the ensuing sterile inflammation have also been attributed a role in HCC pathogenesis. Cargoes of extracellular vesicles (EVs) and/or EVs themselves have been listed among circulating DAMPs but only partially investigated in HCC. Mitochondria-derived vesicles (MDVs), a subpopulation of EVs, are another missing link in the comprehension of the molecular mechanisms underlying the onset and progression of HCC biology. EVs have been involved in HCC growth, dissemination, angiogenesis, and immunosurveillance escape. The contribution of MDVs to these processes is presently unclear. Pyroptosis triggers systemic inflammation through caspase-dependent apoptotic cell death and is implicated in tumor immunity. The analysis of this process, together with MDV characterization, may help capture the relationship among HCC development, mitochondrial quality control, and inflammation. The combination of immune checkpoint inhibitors (i.e., atezolizumab and bevacizumab) has been approved as a synergistic first-line systemic treatment for unresectable or advanced HCC. The lack of biomarkers that may allow prediction of treatment response and, therefore, patient selection, is a major unmet need. Herein, we overview the molecular mechanisms linking mitochondrial dysfunction, inflammation, and pyroptosis, and discuss how immunotherapy targets, at least partly, these routes.
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Carcinoma Hepatocelular , Vesículas Extracelulares , Inflamação , Neoplasias Hepáticas , Mitocôndrias , Piroptose , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Vesículas Extracelulares/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Mitocôndrias/metabolismo , AnimaisRESUMO
Sarcopenia, the age-associated decline in skeletal muscle mass and strength, is a condition with a complex pathophysiology. Among the factors underlying the development of sarcopenia are the progressive demise of motor neurons, the transition from fast to slow myosin isoform (type II to type I fiber switch), and the decrease in satellite cell number and function. Mitochondrial dysfunction has been indicated as a key contributor to skeletal myocyte decline and loss of physical performance with aging. Several systems have been implicated in the regulation of muscle plasticity and trophism such as the fine-tuned and complex regulation between the stimulator of protein synthesis, mechanistic target of rapamycin (mTOR), and the inhibitor of mTOR, AMP-activated protein kinase (AMPK), that promotes muscle catabolism. Here, we provide an overview of the molecular mechanisms linking mitochondrial signaling and quality with muscle homeostasis and performance and discuss the main pathways elicited by their imbalance during age-related muscle wasting. We also discuss lifestyle interventions (i.e., physical exercise and nutrition) that may be exploited to preserve mitochondrial function in the aged muscle. Finally, we illustrate the emerging possibility of rescuing muscle tissue homeostasis through mitochondrial transplantation.
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Sarcopenia , Humanos , Idoso , Sarcopenia/metabolismo , Mitocôndrias/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Músculo Esquelético/metabolismoRESUMO
BACKGROUND AND AIMS: Hypercholesterolemia is frequent in people with primary biliary cholangitis (PBC); however, it does not seem to confer an increased risk of cardiovascular disease. We aimed to evaluate the prevalence of peripheral arterial disease in PBC women and its association with the gut-liver axis and systemic inflammation. METHODS: Thirty patients affected by PBC and hypercholesterolemia were enrolled, with equal-sized groups of women with non-alcoholic fatty liver disease (NAFLD) and healthy controls (CTRL). All patients underwent Doppler ultrasound examination of peripheral arteries, assessment of flow-mediated dilation, quantification of circulating cytokines and vasoactive mediators and characterization of the gut microbiota. RESULTS: PBC patients had a higher prevalence of lower extremity arterial disease (LEAD) defined as atherosclerotic plaques in any of femoral, popliteal and/or tibial arteries compared with both NAFLD and CTRL women (83.3% vs. 53.3% and 50%, respectively; p = .01). Factors associated with LEAD at univariate analysis were VCAM-1 (p = .002), ICAM-1 (p = .003), and TNF-alpha (p = .04) serum levels, but only VCAM-1 (OR 1.1, 95% CI 1.0-1.1; p = .04) and TNF-alpha (OR 1.12, 95% CI 0.99-1.26; p = .04) were confirmed as independent predictors in the multivariate model. Gut microbiota analysis revealed that Acidaminococcus (FDR = 0.0008), Bifidobacterium (FDR = 0.001) and Oscillospira (FDR = 0.03) were differentially expressed among groups. Acidaminococcus, which was increased in PBC, was positively correlated with TNF-alpha serum levels. Down-regulation of metabolic pathways linked to fatty acid and butyrate metabolism, glyoxylate metabolism and branched-chain amino acids degradation was found in the functional gut metagenome of PBC women. CONCLUSIONS: LEAD is common in patients affected by PBC and is associated with inflammatory markers and alterations in the gut-liver axis.
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Aterosclerose , Hipercolesterolemia , Cirrose Hepática Biliar , Hepatopatia Gordurosa não Alcoólica , Humanos , Feminino , Cirrose Hepática Biliar/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Fator de Necrose Tumoral alfa , Hipercolesterolemia/complicações , Prevalência , Molécula 1 de Adesão de Célula Vascular , Aterosclerose/epidemiologia , Aterosclerose/complicações , Extremidade InferiorRESUMO
BACKGROUND: Lifestyle habits have a key role in cardiometabolic health. The effects of combined aerobic training (AT) and high protein intake (HPI) on cardiometabolic parameters in older adults are not well established. AIMS: To investigate the association of AT and HPI with blood pressure (BP), blood glucose, and total blood cholesterol levels in a sample of Italian older adults enrolled in the Longevity Check-up 7 + (Lookup 7 +) study. METHODS: Lookup 7 + is an ongoing project started in June 2015 and conducted in unconventional settings (e.g., exhibitions, malls, health promotion campaigns) across Italy with the aim of fostering adoption of healthy lifestyles in the general population. For the present investigation, analyses were conducted in participants 65 + years and with body mass index values ≥ 18.5 kg/m2 (n = 3219). Systolic (SBP) and diastolic BP (DBP), blood glucose, and total blood cholesterol were measured. Protein intake was estimated using a 12-item food frequency questionnaire. HPI was operationalized as a daily protein intake ≥ 0.8 g/kg of body weight. AT was operationalized as the practice of running and/or swimming for 60 + minutes at least twice weekly during the previous year. RESULTS: The mean age of the 3219 participants was 72.7 ± 5.7 years, and 55.2% were women. Adherence to AT combined with a HPI was negatively and independently associated with SPB (ß: - 4.976; 95% confidence interval: - 9.8 to - 0.08). No other significant associations were observed. DISCUSSION AND CONCLUSIONS: Our results indicate that AT combined with HPI was negatively associated with SBP in a large and relatively unselected sample of Italian older adults living in the community. These findings need confirmation by ad hoc designed studies.
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Glicemia , Hipotensão , Humanos , Feminino , Idoso , Masculino , Estudos Transversais , Pressão Sanguínea/fisiologia , ColesterolRESUMO
Aging is a complex and multifactorial process resulting, at least partly, from the generation and accrual of damage in the setting of reduced resilience [...].
RESUMO
Neurological disorders are a large and heterogeneous field of research that can be tackled through a variety of approaches, ranging from epidemiology to molecular biology, through clinical, biostatistical, and laboratory experiments [...].
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Doenças do Sistema Nervoso , Humanos , Doenças do Sistema Nervoso/genética , Biologia Molecular , LaboratóriosRESUMO
Mitophagy is crucial for maintaining mitochondrial quality. However, its assessment in vivo is challenging. The endosomal-lysosomal system is a more accessible pathway through which subtypes of extracellular vesicles (EVs), which also contain mitochondrial constituents, are released for disposal. The inclusion of mitochondrial components into EVs occurs in the setting of mild mitochondrial damage and during impairment of lysosomal function. By releasing mitochondrial-derived vesicles (MDVs), cells limit the unload of mitochondrial damage-associated molecular patterns with proinflammatory activity. Both positive and negative effects of EVs on recipient cells have been described. Whether this is due to the production of EVs other than those containing mitochondria, such as MDVs, holding specific biological functions is currently unknown. Evidence on the existence of different MDV subtypes has been produced. However, their characterization is not always pursued, which would be relevant to exploring the dynamics of mitochondrial quality control in health and disease. Furthermore, MDV classification may be instrumental in understanding their biological roles and promoting their implementation as biomarkers in clinical studies.
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Vesículas Extracelulares , Mitocôndrias , Alarminas , Endossomos , MitofagiaRESUMO
Altered l-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of l-arginine, citrulline, ornithine, monomethyl-l-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of l-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV-2-infection. l-arginine-derived markers of nitric oxide (NO) bioavailability (i.e., l-arginine/ADMA, l-arginine/citrulline+ornithine, and l-arginine/ornithine) were also assayed. Partial least squares discriminant analysis (PLS-DA) models were built to characterize systemic l-arginine metabolism and assess the effects of the supplementation. PLS-DA allowed discrimination of participants with long COVID from healthy controls with 80.2 ± 3.0% accuracy. Lower markers of NO bioavailability were found in participants with long COVID. After 28 days of l-arginine plus vitamin C supplementation, serum l-arginine concentrations and l-arginine/ADMA increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , Adulto , Ácido Ascórbico/uso terapêutico , Citrulina/metabolismo , SARS-CoV-2/metabolismo , Arginina/metabolismo , Óxido Nítrico/metabolismo , Ornitina , Suplementos NutricionaisRESUMO
PURPOSE OF REVIEW: Multisystem derangements, encompassing metabolic, musculoskeletal and stress-response systems, occur during aging and are associated with the development of physical frailty and sarcopenia. These modular changes are relevant sources for the identification of biomarkers for the two conditions. Here, we provide an up-to-date overview on existing biomarkers of physical frailty and sarcopenia and discuss emerging approaches for biomarker discovery. RECENT FINDINGS: Inflammatory, metabolic and hematologic markers are shared between physical frailty and sarcopenia. Gut microbial derivatives and damage-associated molecular patterns transferred via extracellular vesicles have been indicated as possible gut-muscle axis regulators and candidate markers of physical frailty and sarcopenia. SUMMARY: Mediators of metabolic, musculoskeletal and stress-response system dysregulation are shared by physical frailty and sarcopenia and indicate the existence of common pathophysiological pathways. Multiplatform biomarker analyses have been proposed as an innovating approach for tracking the multifaceted and dynamic nature of physical frailty and sarcopenia. Upon validation, the identified biomarkers may support diagnostic makeup and tracking of the two conditions in both research and clinical settings.
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Pesquisa Biomédica , Fragilidade , Sarcopenia , Idoso , Envelhecimento/fisiologia , Biomarcadores , Idoso Fragilizado , Fragilidade/diagnóstico , HumanosRESUMO
BACKGROUND: Sarcopenia is associated with adverse outcomes in older people. Several tools are recommended to assess muscle mass, muscle strength and physical performance, but are not always available in daily practice. OBJECTIVE: The aim of the present study is to evaluate if there is a correlation between the personal perception of physical performance (assessed through a question on personal functional status) and the effective presence of sarcopenia (according to the EWGSOP2 definition) using data from the Longevity Check-up 7 + project. DESIGN: Cross-sectional study. SETTING: The Longevity Check-up 7 + project is an ongoing study started in June 2015 and conducted in unconventional settings (i.e., exhibitions, malls, and health promotion campaigns). SUBJECTS: Candidate participants are eligible for enrollment if they are at least 18 years of age and provide written informed consent. For the present study subjects 65 years age old and older have been considered (n = 2901). METHODS: According to the most recent EWGSOP2 consensus definition, subjects were defined to be affected by probable sarcopenia when handgrip strength was less than 27 kg in male and less than 16 kg in female, respectively. Furthermore, a single question assessed the perceived health status regarding own physical performance: "Do you have any difficulty in walking 400 m?". RESULTS: Using the EWGSOP2 algorithm, 529 (18,9%) participants were identified as affected by probable sarcopenia with a significant higher prevalence among subjects with self-reported difficulty in walking 400 m compared to participant without any difficulty (33.6% versus 13.1%, respectively; p < 0.001). Relative to participants without self-reported difficulty, those subjects with self-reported difficulty in walking 400 m showed a significantly higher risk of sarcopenia (odds ratio [OR]: 3.34; 95% confidence interval [CI]: 2.75-4.07). CONCLUSIONS: A single "Red Flag" question such as "Do you have any difficulty in walking 400 m?" should be considered as a recommended method for screening probable sarcopenia risk.
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Sarcopenia , Idoso , Estudos Transversais , Feminino , Força da Mão/fisiologia , Humanos , Masculino , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Autorrelato , CaminhadaRESUMO
BACKGROUND: Cardiovascular disease still represents the leading cause of death worldwide. Management of risk factors remains crucial; despite this, hypercholesterolemia, which is one of the most important modifiable cardiovascular risk factor, is still high prevalent in general population. The aim of this study is to determine the prevalence of dyslipidemia and hypercholesterolemia awareness in a very large population. METHODS: More than 65 000 users completed the online, self-administered survey. It was structured like a 'journey' where each stage corresponded to a cardiovascular risk factor: blood pressure, body mass index, cholesterol, diet, physical exercise, smoke and blood sugar. At the end, the user received a final evaluation of his health status. RESULTS: The mean age was 52.5 years (SD 13.9, range 18-98), with 35 402 (53.7%) men. About 56% of all participants believed to have normal cholesterol values, when only 40% of them really showed values <200 mg/dl. Only about 30% of all participants self-predicted to have abnormal cholesterol values whereas we found high cholesterol levels in about 60% of people. CONCLUSIONS: Dyslipidemia is very prevalent and half of the people with high cholesterol is not aware of having high values.