Background:Mammalian cells possess molecular clocks,the adequate functioning of which is decisive for metabolic health.Exercise is known to modulate these clocks,potentially having distinct effects on metabolism depen...Background:Mammalian cells possess molecular clocks,the adequate functioning of which is decisive for metabolic health.Exercise is known to modulate these clocks,potentially having distinct effects on metabolism depending on the time of day.This study aimed to investigate the impact of morning vs.evening moderate-intensity aerobic exercise on glucose regulation and energy metabolism in healthy men and women.It also aimed to elucidate molecular mechanisms within skeletal muscle.Methods:Using a randomized crossover design,healthy men(n=18)and women(n=17)performed a 60-min bout of moderate-intensity aerobic exercise in the morning and evening.Glucose regulation was continuously monitored starting 24 h prior to the exercise day and continuing until 48 h post-exercise for each experimental condition.Energy expenditure and substrate oxidation were measured by indirect calorimetry during exercise and at rest before and after exercise for 30 min.Skeletal muscle biopsies were collected immediately before and after exercise to assess mitochondrial function,transcriptome,and mitochondrial proteome.Results:Results indicated similar systemic glucose,energy expenditure,and substrate oxidation during and after exercise in both sexes.Notably,transcriptional analysis,mitochondrial function,and mitochondrial proteomics revealed marked sexual dimorphism and time of day variations.Conclusion:The sexual dimorphism and time of day variations observed in the skeletal muscle in response to exercise may translate into observable systemic effects with higher exercise-intensity or chronic exercise interventions.This study provides a foundational molecular framework for precise exercise prescription in the clinical setting.展开更多
Dementia is one of the greatest global challenges for health and social care in the 21st century.Alzheimer’s disease(AD),the most common type of dementia,is by no means an inevitable consequence of growing old.Severa...Dementia is one of the greatest global challenges for health and social care in the 21st century.Alzheimer’s disease(AD),the most common type of dementia,is by no means an inevitable consequence of growing old.Several lifestyle factors may increase,or reduce,an individual’s risk of developing AD.Much has been written over the ages about the benefits of exercise and physical activity.Among the risk factors associated with AD is a low level of physical activity.The relationship between physical and mental health was established several years ago.In this review,we discuss the role of exercise(aerobic and resistance)training as a therapeutic strategy for the treatment and prevention of AD.Older adults who exercise are more likely to maintain cognition.We address the main protective mechanism on brain function modulated by physical exercise by examining both human and animal studies.We will pay especial attention to the potential role of exercise in the modulation of amyloid b turnover,inflammation,synthesis and release of neurotrophins,and improvements in cerebral blood flow.Promoting changes in lifestyle in presymptomatic and predementia disease stages may have the potential for delaying one-third of dementias worldwide.Multimodal interventions that include the adoption of an active lifestyle should be recommended for older populations.展开更多
Background Cardiorespiratory fitness(CRF)is inversely associated with mortality in apparently healthy subjects and in some clinical populations,but evidence for the association between CRF and all-cause and/or cardiov...Background Cardiorespiratory fitness(CRF)is inversely associated with mortality in apparently healthy subjects and in some clinical populations,but evidence for the association between CRF and all-cause and/or cardiovascular disease(CVD)mortality in patients with established CVD is lacking.This study aimed to quantify this association.Methods We searched for prospective cohort studies that measured CRF with cardiopulmonary exercise testing in patients with CVD and that examined all-cause and CVD mortality with at least 6 months of follow-up.Pooled hazard ratios(HRs)were calculated using random-effect inverse-variance analyses.Results Data were obtained from 21 studies and included 159,352 patients diagnosed with CVD(38.1%female).Pooled HRs for all-cause and CVD mortality comparing the highest vs.lowest category of CRF were 0.42(95%confidence interval(95%CI):0.28–0.61)and 0.27(95%CI:0.16–0.48),respectively.Pooled HRs per 1 metabolic equivalent(1-MET)increment were significant for all-cause mortality(HR=0.81;95%CI:0.74–0.88)but not for CVD mortality(HR=0.75;95%CI:0.48–1.18).Coronary artery disease patients with high CRF had a lower risk of all-cause mortality(HR=0.32;95%CI:0.26–0.41)than did their unfit counterparts.Each 1-MET increase was associated with lower all-cause mortality risk among coronary artery disease patients(HR=0.83;95%CI:0.76–0.91)but not lower among those with heart failure(HR=0.69;95%CI:0.36–1.32).Conclusion A better CRF was associated with lower risk of all-cause mortality and CVD.This study supports the use of CRF as a powerful predictor of mortality in this population.展开更多
Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.Methods:A systematic search for relevant studie...Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.Methods:A systematic search for relevant studies was performed in 3 databases.Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included:adiponectin,apelin,brain-derived neurotrophic factor,fetuin-A,fibroblast growth factor-21,follistatin,ghrelin,interleukin(IL)-6,IL-8,IL-10,IL-15,IL-18,leptin,myostatin,omentin,resistin,retinol-binding protein 4,tumor necrosis factor-α,and visfatin.Results:Forty randomized controlled trials were selected for data extraction(n=2160).Exercise training induces changes in adiponectin,fetuin-A,fibroblast growth factor-21,IL-6,IL-10,leptin,resistin,and tumor necrosis factor-a levels but has no significant effects on apelin,IL-18,and ghrelin compared to controls.Physical exercise training favored large and positive changes in pooled exerkines(i.e.,an overall effect size calculated from several exerkine s)(Hedge’s g=1.02,95%confidence interval(95%CI):0.76-1.28),which in turn were related to changes in glycated hemoglobin(mean difference(MD)=-0.81%,95%CI:-0.95%to-0.67%),fasting glucose(MD=-23.43 mg/dL,95%CI:-30.07 mg/dL to-16.80 mg/dL),waist circumference(MD=-3.04 cm,95%CI:-4.02 cm to-2.07 cm),and body mass(MD=-1.93 kg,95%CI:-2.00 kg to-1.86 kg).Slightly stronger effects were observed with aerobic,resistance,or high-intensity interval protocols at moderate-to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session.Conclusion:Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.展开更多
The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulat...The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and hematopoiesis.Curiously,the regenerative effect of MSC is partly due to their paracrine activity.This has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient cells.Interestingly,contents of EV can be modulated by preconditioning MSC under different culture conditions.Among them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) concentrations.HIF has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell apoptosis.Expression of these genes is reflected in the contents of secreted EV.Interestingly,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia.In this review,we show the implications of hypoxia responses in relation to tissue regeneration.In addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.展开更多
Purpose:This study aimed to examine the associations of accelerometer-derived steps volume and intensity with hospitalizations and all-cause mortality in older adults.Methods:This prospective cohort study involved 768...Purpose:This study aimed to examine the associations of accelerometer-derived steps volume and intensity with hospitalizations and all-cause mortality in older adults.Methods:This prospective cohort study involved 768 community-dwelling Spanish older adults(78.8±4.9 years,mean±SD;53.9% females)from the Toledo Study for Healthy Aging(2012-2017).The number of steps per day and step cadence(steps/min) were derived from a hip-mounted accelerometer worn for at least 4 days at baseline.Participants were followed-up over a mean period of 3.1 years for hospitalization and 5.7 years for all-cause mortality.Cox proportional hazards regression models were used to estimate the individual and joint associations between daily steps and stepping intensity with hospitalizations and all-cause mortality.Results:Included participants walked 5835± 3445 steps/day with an intensity of 7.3± 4.1 steps/min.After adjusting for age,sex,body mass index(BMI),education,income,marital status and comorbidities,higher step count(hazard ratio(HR)=0.95,95% confidence interval(95%CI:0.90-1.00,and HR=0.87,95%CI:0.81-0.95 per additional 1000 steps) and higher step intensity(HR=0.95,95%CI:0.91-0.99,and HR=0.89,95%CI:0.84-0.95 per each additional step/min) were associated with fewer hospitalizations and all-cause mortality risk,respectively.Compared to the group having low step volume and intensity,individuals in the group having high step volume and intensity had a lower risk of hospitalization(HR=0.72,95%CI:0.52-0.98) and all-cause mortality(HR=0.60,95%CI:0.37-0.98).Conclusion:Among older adults,both high step volume and step intensity were significantly associated with lower hospitalization and all-cause mortality risk.Increasing step volume and intensity may benefit older people.展开更多
Background Elderly patients with non-ST-segment elevation acute coronary syndromes(NSTE-ACS)may present delirium but its clinical relevance is unknown.This study aimed at detennining the clinical associated factors,an...Background Elderly patients with non-ST-segment elevation acute coronary syndromes(NSTE-ACS)may present delirium but its clinical relevance is unknown.This study aimed at detennining the clinical associated factors,and prognostic implications of delirium in old-aged patients admitted for NSTE-ACS.Methods LONGEVO-SCA is a prospective multicenter registry including unselected patients with NSTE-ACS aged>80 years.Clinical variables and a complete geriatric evaluation were assessed during hospitalization.The association between delirium and 6-month mortality was assessed by a Cox regression model weighted for a propensity score including the potential confounding variables.We also analysed its association with 6-month bleeding and cognitive or functional decline.Results Among 527 patients included,thirty-seven(7%)patients presented delirium during the hospitalization.Delirium was more frequent in patients with dementia or depression and in those from nursing homes(27.0%vs.3.1%,24.3%vs.11.6%,and 11.1%V5.2.2%,respectively;all P<0.05).Delirium was significantly associated with in-hospital infections(27.0%vs.5.3%,P<0.001)and usage of diuretics(70.3%vs.49.8%,P=0.02).Patients with delirium had longer hospitalizations[median 8.5(5.5-14)vs.6.0(4.0-10)days,P=0.02]and higher incidence of 6-month bleeding and mortality(32.3%vs.10.0%and 24.3%vs.10.8%,respectively;both P<0.05)but similar cognitive or functional decline.Delirium was independently associated with 6-month mortality(HR=1.47,95%CI:1.02-2.13,P=0.04)and 6-month bleeding events(OR=2.87;95%CI:1.98-4」6,P<0.01).Conclusions In-hospital delirium in elderly patients with NSTE-ACS is associated with some preventable risk factors and it is an independent predictor of 6-month mortality.展开更多
Non-alcoholic fatty liver disease(NAFLD)prevalence has increased drastically in recent decades,affecting up to 25%of the world’s population.NAFLD is a spectrum of different diseases that starts with asymptomatic stea...Non-alcoholic fatty liver disease(NAFLD)prevalence has increased drastically in recent decades,affecting up to 25%of the world’s population.NAFLD is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis,which can progress to fibrosis.Several molecular and metabolic changes are required for the hepatocyte to finally vary its function;hence a“multiple hit”hypothesis seems a more accurate proposal.Previous studies and current knowledge suggest that in most cases,NAFLD initiates and progresses through most of nine hallmarks of the disease,although the triggers and mechanisms for these can vary widely.The use of animal models remains crucial for understanding the disease and for developing tools based on biological knowledge.Among certain requirements to be met,a good model must imitate certain aspects of the human NAFLD disorder,be reliable and reproducible,have low mortality,and be compatible with a simple and feasible method.Metabolism studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the disease.Metabolomics seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological understanding.In this review,we provide a brief introduction to NAFLD hallmarks,the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD.展开更多
Extra virgin olive oil is characterized by its high content of unsaturated fatty acid residues in triglycerides,mainly oleic acid,and the presence of bioactive and antioxidant compounds.Its consumption is associated w...Extra virgin olive oil is characterized by its high content of unsaturated fatty acid residues in triglycerides,mainly oleic acid,and the presence of bioactive and antioxidant compounds.Its consumption is associated with lower risk of suffering chronic diseases and unwanted processes linked to aging,due to the antioxidant capacity and capability of its components to modulate cellular signaling pathways.Consumption of olive oil can alter the physiology of mesenchymal stem cells(MSCs).This may explain part of the healthy effects of olive oil consumption,such as prevention of unwanted aging processes.To date,there are no specific studies on the action of olive oil on MSCs,but effects of many components of such food on cell viability and differentiation have been evaluated.The objective of this article is to review existing literature on how different compounds of extra virgin olive oil,including residues of fatty acids,vitamins,squalene,triterpenes,pigments and phenols,affect MSC maintenance and differentiation,in order to provide a better understanding of the healthy effects of this food.Interestingly,most studies have shown a positive effect of these compounds on MSCs.The collective findings support the hypothesis that at least part of the beneficial effects of extra virgin olive oil consumption on health may be mediated by its effects on MSCs.展开更多
Background: Evidence shows an association between grip strength and health;however, grip strength cut-offs for the detection of metabolic syndrome(MetS) in Latin American populations are scarce. The purpose of this st...Background: Evidence shows an association between grip strength and health;however, grip strength cut-offs for the detection of metabolic syndrome(MetS) in Latin American populations are scarce. The purpose of this study was to determine cut-offs of normalized grip strength(NGS)for the detection of MetS in a large nonrepresentative sample of a collegiate student population from Colombia.Methods: A total of 1795 volunteers(61.4% female;age = 20.68 ± 3.10 years, mean ± SD), ranging between 18 and 30 years of age participated in the study. Strength was estimated using a handheld dynamometer and normalized to body mass(handgrip strength(kg)/body mass(kg)). Anthropometrics, serum lipids indices, blood pressure, and fasting plasma glucose were measured. Body composition was measured by bioelectrical impedance analysis. MetS was defined as including ≥3 of the 5 metabolic abnormalities according to the International Diabetes Federation definition. A metabolic risk score was computed from the following components: waist circumference, triglycerides, high-density lipoprotein cholesterol, glucose, and systolic and diastolic blood pressure.Results: Receiver operating curve analysis showed significant discriminatory accuracy of NGS in identifying the thresholds and risk categories.Lower strength was associated with increased prevalence of MetS. In males, weak, intermediate, and strong NGS values at these points were<0.466, 0.466-0.615, >0.615, respectively. In females, these cut-off points were <0.332, 0.332-0.437, >0.437, respectively.Conclusion: Our sex-specific cut-offs of NGS could be incorporated into a clinical setting for identifying college students at cardiometabolic disease risk.展开更多
Dear Editor,We have read with interest the commentary by McAvoy and Tudor-Locke on our article entitled "Association of accelerometer-derived step volume and intensity with ho spitalizations and mortality in olde...Dear Editor,We have read with interest the commentary by McAvoy and Tudor-Locke on our article entitled "Association of accelerometer-derived step volume and intensity with ho spitalizations and mortality in older adults:A prospective cohort study". The authors expressed some concerns about our methodology used to define accelerometer-derived step intensity and the analytical approach applied in our study.展开更多
Objectives To assess the effects of an exercise training program combining power-oriented resistance training(RT)and high-intensity interval training(HIIT)on metabolic syndrome(MetS)markers in older people with COPD.M...Objectives To assess the effects of an exercise training program combining power-oriented resistance training(RT)and high-intensity interval training(HIIT)on metabolic syndrome(MetS)markers in older people with COPD.Methods Twenty-nine older people(66–90 years old)with COPD were randomly assigned to 12 weeks of exercise training(ET;power-oriented RT+HIIT)or a control group(CON).Waist circumference,diastolic(DBP)and systolic blood pressure(SBP),and serum fasting glucose,triglycerides and HDL cholesterol levels were assessed at baseline and after 12 weeks.Linear mixed-effects models were used to assess the effects of the intervention,and data were reported as mean and 95%confidence interval values.Results Waist circumference increased in the CT group,but not in the ET group(2.0[0.2,3.7]vs.1.0[−1.3,3.2]cm,respectively).No changes in fasting glucose(−4.1[−10.3,2.1]vs.−1.0[−8.7,6.7]mg dL−1),triglycerides(3.9[−13.4,21.3]vs.−13.9[−35.6,7.7]mg dL−1)or HDL cholesterol(1.0[−3.4,5.4]vs.2.9[−2.6,8.4]mg dL−1)were found in the CT or ET group,respectively.The ET group exhibited decreased DBP(−5.2[−9.5,−0.8]mmHg)and SBP(−2.7[−22.7,−2.7]mmHg),while no changes were found in the CT group(0.3[−3.2,3.7]and−3.5[−11.4,4.5]mmHg).MetS z-score declined in ET but remained unchanged in CT(−0.88[−1.74,−0.03]vs.0.07[−0.62,0.76],respectively).Conclusions A 12-week exercise training program led to a reduction in blood pressure and MetS z-score in older people with COPD.展开更多
BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and adipocytes.MSC tend to differentiate into adipocytes,instead of osteoblasts,with aging.This favors the loss of bone mass and d...BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and adipocytes.MSC tend to differentiate into adipocytes,instead of osteoblasts,with aging.This favors the loss of bone mass and development of osteoporosis.Hypoxia induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and angiogenesis.That allows a better adaptation to low O2 conditions.Sustained hypoxia has negative effects on bone metabolism,favoring bone resorption.Yet,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in aging.AIM To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in elderly.METHODS MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,respectively.In addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain reaction.The in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray absorptiometry.RESULTS CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,respectively.However,both parameters were not significantly affected by the other shorter hypoxia times assessed.The longest periods of hypoxia downregulated the expression of genes related to extracellular matrix formation,in MSC induced to differentiate into osteoblasts.Interestingly,osteocalcin(associated to energy metabolism)was upregulated.Vascular endothelial growth factor an expression and low-density lipoprotein receptor related protein 5/6/dickkopf Wnt signaling pathway inhibitor 1(associated to Wnt/β-catenin pathway activation)increased in osteoblasts.Yet,they decreased in adipocytes after CH treatments,mainly with the longest hypoxia times.However,the same CH treatments increased the osteoprotegerin/receptor activator for nuclear factor kappa B ligand ratio in both cell types.An increase in total bone mineral density was observed in elderly people exposed to CH,but not in specific regions.The percentage of fat did not vary between groups.CONCLUSION CH may have positive effects on bone health in the elderly,due to its possible inhibitory effect on bone resorption,by increasing the osteoprotegerin/receptor activator for nuclear factor kappa B ligand ratio.展开更多
Purpose:The present work examines the associations of dietary habits,sedentarism,physical activity(PA)levels and sleep habits,with thyroid function in young euthyroid adults.Methods:A total of 105 young euthyroid adul...Purpose:The present work examines the associations of dietary habits,sedentarism,physical activity(PA)levels and sleep habits,with thyroid function in young euthyroid adults.Methods:A total of 105 young euthyroid adults participated in this cross-sectional study.Thyroid function was determined in fasting conditions(>6 h).Dietary habits were measured by a food frequency questionnaire and three non-consecutive 24 h recalls,and different dietary intake and patterns were then estimated.The time spent in sedentary,PA levels and sleep habits were objectively measured using a wrist-worn accelerometer.Results:Energy and carbohydrate intake were positively associated with thyroid stimulating hormone(TSH)(β=0.222;R^(2)=0.102;P=0.022 andβ=0.425;R^(2)=0.129;P=0.007,respectively)whereas fat intake was negatively associated with TSH(β=-0.428;R^(2)=0.137;P=0.004).Energy intake was also positively associated with free triiodothyronine(β=0.277;R^(2)=0.137;P=0.004).Further,adherence to the Mediterranean diet was negatively related to TSH and free thyroxine(FT4)(β=-0.221;R^(2)=0.113;P=0.020 andβ=-0.268;R^(2)=0.071;P=0.007,respectively).Vigorous-intensity and overall PA were negatively associated with FT4(β=-0.227;R^(2)=0.052;P=0.022 andβ=-0.204;R^(2)=0.042;P=0.041,respectively).In contrast,no associations were found between sleep parameters and thyroid function.Conclusions:Lifestyle factors such as dietary intake and PA levels seems to be related to thyroid function even in young euthyroid adults.展开更多
Nuclear receptor subfamily 1,group D,member 1(NR1D1,also known as REV-ERBα)belongs to the nuclear receptor(NR)family,and is a heme-binding component of the circadian clock that consolidates circadian oscillators.In a...Nuclear receptor subfamily 1,group D,member 1(NR1D1,also known as REV-ERBα)belongs to the nuclear receptor(NR)family,and is a heme-binding component of the circadian clock that consolidates circadian oscillators.In addition to repressing the transcription of multiple clock genes associated with circadian rhythms,NR1D1 has a wide range of downstream target genes that are intimately involved in many physiopathological processes,including autophagy,immunity,inflammation,metabolism,and aging in multiple organs.This review focuses on the pivotal role of NR1D1 as a key transcription factor in the gene regulatory network,with particular emphasis on the milestones of the latest discoveries of NR1D1 ligands.NR1D1 is considered as a promising drug target for treating diverse diseases and may contribute to research on innovative biomarkers and therapeutic targets for organ injury-related diseases.Further research on NR1D1 ligands in prospective human trials may pave the way for their clinical application in many organ injury-related disorders.展开更多
In a recent study published in Cell,Woo et al.1 investigated the role of the immunoproteasome and the metabolic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)in neurons in the context of mult...In a recent study published in Cell,Woo et al.1 investigated the role of the immunoproteasome and the metabolic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)in neurons in the context of multiple sclerosis(MS)-related IFNγsignaling,finding new therapeutic targets for neurodegeneration in MS and possibly other related neuroinflammatory neurodegenerative disorders.展开更多
The SARS-CoV-2-caused COVID-19 pandemic has resulted in a devastating threat to human society in terms of health,economy,and lifestyle.Although the virus usually first invades and infects the lung and respiratory trac...The SARS-CoV-2-caused COVID-19 pandemic has resulted in a devastating threat to human society in terms of health,economy,and lifestyle.Although the virus usually first invades and infects the lung and respiratory track tissue,in extreme cases,almost all major organs in the body are now known to be negatively impacted often leading to severe systemic failure in some people.Unfortunately,there is currently no effective treatment for this disease.Pre-existing pathological conditions or comorbidities such as age are a major reason for premature death and increased morbidity and mortality.The immobilization due to hospitalization and bed rest and the physical inactivity due to sustained quarantine and social distancing can downregulate the ability of organs systems to resist to viral infection and increase the risk of damage to the immune,respiratory,cardiovascular,musculoskeletal systems and the brain.The cellular mechanisms and danger of this“second wave”effect of COVID-19 to the human body,along with the effects of aging,proper nutrition,and regular physical activity,are reviewed in this article.展开更多
Cocoa is the main component of chocolate.It is widely accepted that cocoa quality largely depends on the processing,especially the fermentation step.Traditionally,fermentation takes place spontaneously by the endogeno...Cocoa is the main component of chocolate.It is widely accepted that cocoa quality largely depends on the processing,especially the fermentation step.Traditionally,fermentation takes place spontaneously by the endogenous microbiota;however,the process can lead to poor quality and heterogeneity of the final product.In this study,we evaluated the influence of the starter culture on the profile of volatiles during fermentation of commercial volumes of Mexican cocoa.Volatiles were also analyzed in post-fermented cocoa samples obtained after drying,roasting,and conching.Our results revealed a most desirable volatile profile in cocoa fermented with starter culture,mainly due to the higher relative content of alcohols(40%)and aldehydes(3.5%),but also due to a lower acidity(<1%)as compared to endogenous fermentation(acids,65%;alcohols,2%;and aldehydes<0.5%).Additionally,it is remarkable,the higher content of pyrazines in the inoculated samples after processing.展开更多
Demographic aging is one of the most serious challenges facing our society.Although we live longer,we do not live better because it is considered that approximately 16–20%of our life is spent in late-life morbidity.O...Demographic aging is one of the most serious challenges facing our society.Although we live longer,we do not live better because it is considered that approximately 16–20%of our life is spent in late-life morbidity.Older people have the greatest risk of developing frailty increasing the risk of presenting various adverse health events such as low quality of life,disability,hospitalization and even death.Frail men and women over 65 years old have lower muscle quality and muscle mass and higher percentage of body fat than non-frail people of the same age.In this review we will address the main physiological changes in the muscular and nervous system associated to aging.More specifically we will review the changes in muscle mass,quality,and strength relating them with the decrease in capillarization and muscular oxidative capacity as well as with the alterations in protein synthesis in the muscle with aging.The last section of the manuscript will be devoted to the animal models of frailty and the indexes developed to measure frailty in these models.We will finally address the importance of exercise training as an intervention to delay or even reverse frailty.展开更多
基金funded by the Spanish Ministry of Culture and Sport,Consejo Superior de Deportes,Plan de Recuperación,Transformación y Resiliencia,Unión Europea,Next Generation EUAyudas Europeas a Proyectos de Investigaci on Aplicada a la Actividad Física Beneficiosa para la Salud y la Medicina Deportiva(EXP_77437)+9 种基金by the Spanish Ministry of Science and Innovation(PID2022-141506OB-I00)the European Regional Development Funds(ERDF)by the University of Granada Plan Propio de Investigación-Excellence actions:Unit of Excellence on Exercise Nutrition and Health(UCEENS)supported by the Spanish Ministry of Education,Culture and Sport(FPU19/03745 and FPU20/05530,respectively)supported by the Juan de la Cierva Formación Grant FJC2020-044453-I funded by Ministerio de Ciencia e Innovaci on/Agencia Estatal de Investigaci on MCIN/AEI/10.13039/501100011033European Union Next Generation,Plan de Recuperación,Transformación y Resilencia(EU/PRTR)“Ramón y Cajal fellowship 2013-2017”funded by MCIN/AEI/10.13039/501100011033 and“El Fondo Social Europeo invierte en tu futuro”partially supported by the Grant PID2020-114054RA-I001001100482funded by MCIN/AEI/10.13039/501100011033supported by a grant from the MCIN/AEI/10.13039/501100011033,Spain,and the ERDF(PID2021-126788OB-I00).
文摘Background:Mammalian cells possess molecular clocks,the adequate functioning of which is decisive for metabolic health.Exercise is known to modulate these clocks,potentially having distinct effects on metabolism depending on the time of day.This study aimed to investigate the impact of morning vs.evening moderate-intensity aerobic exercise on glucose regulation and energy metabolism in healthy men and women.It also aimed to elucidate molecular mechanisms within skeletal muscle.Methods:Using a randomized crossover design,healthy men(n=18)and women(n=17)performed a 60-min bout of moderate-intensity aerobic exercise in the morning and evening.Glucose regulation was continuously monitored starting 24 h prior to the exercise day and continuing until 48 h post-exercise for each experimental condition.Energy expenditure and substrate oxidation were measured by indirect calorimetry during exercise and at rest before and after exercise for 30 min.Skeletal muscle biopsies were collected immediately before and after exercise to assess mitochondrial function,transcriptome,and mitochondrial proteome.Results:Results indicated similar systemic glucose,energy expenditure,and substrate oxidation during and after exercise in both sexes.Notably,transcriptional analysis,mitochondrial function,and mitochondrial proteomics revealed marked sexual dimorphism and time of day variations.Conclusion:The sexual dimorphism and time of day variations observed in the skeletal muscle in response to exercise may translate into observable systemic effects with higher exercise-intensity or chronic exercise interventions.This study provides a foundational molecular framework for precise exercise prescription in the clinical setting.
基金TagedPThis work was supported by the following grants:Instituto de Salud Carlos III and co-funded by FEDER(Grant number PIE15/00013)SAF2016-75508-R from the Spanish Ministry of Education and Science(MEC)+2 种基金CB16/10/00435(CIBERFES)PROMETEOII2014/056 from Conselleria,de Sanitat de la Generalitat Valenciana and EU Funded CM1001 and FRAILOMICHEALTH.2012.2.1.1-2ADVANTAGE-724099 Join Action(HP-JA)3rd EU Health Programme and DIALBFRAIL-LATAM(825546 H2020-SC1-BHC).
文摘Dementia is one of the greatest global challenges for health and social care in the 21st century.Alzheimer’s disease(AD),the most common type of dementia,is by no means an inevitable consequence of growing old.Several lifestyle factors may increase,or reduce,an individual’s risk of developing AD.Much has been written over the ages about the benefits of exercise and physical activity.Among the risk factors associated with AD is a low level of physical activity.The relationship between physical and mental health was established several years ago.In this review,we discuss the role of exercise(aerobic and resistance)training as a therapeutic strategy for the treatment and prevention of AD.Older adults who exercise are more likely to maintain cognition.We address the main protective mechanism on brain function modulated by physical exercise by examining both human and animal studies.We will pay especial attention to the potential role of exercise in the modulation of amyloid b turnover,inflammation,synthesis and release of neurotrophins,and improvements in cerebral blood flow.Promoting changes in lifestyle in presymptomatic and predementia disease stages may have the potential for delaying one-third of dementias worldwide.Multimodal interventions that include the adoption of an active lifestyle should be recommended for older populations.
基金AGH is a Miguel Servet Fellow at the Instituto de Salud Carlos III(CP18/0150)RRV is funded in part by a Postdoctoral Fellowship(Resolution ID 420/2019)from the Universidad Pública de Navarra.
文摘Background Cardiorespiratory fitness(CRF)is inversely associated with mortality in apparently healthy subjects and in some clinical populations,but evidence for the association between CRF and all-cause and/or cardiovascular disease(CVD)mortality in patients with established CVD is lacking.This study aimed to quantify this association.Methods We searched for prospective cohort studies that measured CRF with cardiopulmonary exercise testing in patients with CVD and that examined all-cause and CVD mortality with at least 6 months of follow-up.Pooled hazard ratios(HRs)were calculated using random-effect inverse-variance analyses.Results Data were obtained from 21 studies and included 159,352 patients diagnosed with CVD(38.1%female).Pooled HRs for all-cause and CVD mortality comparing the highest vs.lowest category of CRF were 0.42(95%confidence interval(95%CI):0.28–0.61)and 0.27(95%CI:0.16–0.48),respectively.Pooled HRs per 1 metabolic equivalent(1-MET)increment were significant for all-cause mortality(HR=0.81;95%CI:0.74–0.88)but not for CVD mortality(HR=0.75;95%CI:0.48–1.18).Coronary artery disease patients with high CRF had a lower risk of all-cause mortality(HR=0.32;95%CI:0.26–0.41)than did their unfit counterparts.Each 1-MET increase was associated with lower all-cause mortality risk among coronary artery disease patients(HR=0.83;95%CI:0.76–0.91)but not lower among those with heart failure(HR=0.69;95%CI:0.36–1.32).Conclusion A better CRF was associated with lower risk of all-cause mortality and CVD.This study supports the use of CRF as a powerful predictor of mortality in this population.
文摘Background:This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.Methods:A systematic search for relevant studies was performed in 3 databases.Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included:adiponectin,apelin,brain-derived neurotrophic factor,fetuin-A,fibroblast growth factor-21,follistatin,ghrelin,interleukin(IL)-6,IL-8,IL-10,IL-15,IL-18,leptin,myostatin,omentin,resistin,retinol-binding protein 4,tumor necrosis factor-α,and visfatin.Results:Forty randomized controlled trials were selected for data extraction(n=2160).Exercise training induces changes in adiponectin,fetuin-A,fibroblast growth factor-21,IL-6,IL-10,leptin,resistin,and tumor necrosis factor-a levels but has no significant effects on apelin,IL-18,and ghrelin compared to controls.Physical exercise training favored large and positive changes in pooled exerkines(i.e.,an overall effect size calculated from several exerkine s)(Hedge’s g=1.02,95%confidence interval(95%CI):0.76-1.28),which in turn were related to changes in glycated hemoglobin(mean difference(MD)=-0.81%,95%CI:-0.95%to-0.67%),fasting glucose(MD=-23.43 mg/dL,95%CI:-30.07 mg/dL to-16.80 mg/dL),waist circumference(MD=-3.04 cm,95%CI:-4.02 cm to-2.07 cm),and body mass(MD=-1.93 kg,95%CI:-2.00 kg to-1.86 kg).Slightly stronger effects were observed with aerobic,resistance,or high-intensity interval protocols at moderate-to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session.Conclusion:Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.
基金Supported by “Instituto de Salud Carlos III”(ISCIII)“Ministerio de Economía y Competitividad”(MINECO) and European Union (EU),No. PI18/01659 and No. PI21/01935
文摘The use of mesenchymal stem-cells(MSC)in cell therapy has received considerable attention because of their properties.These properties include high expansion and differentiation in vitro,low immunogenicity,and modulation of biological processes,such as inflammation,angiogenesis and hematopoiesis.Curiously,the regenerative effect of MSC is partly due to their paracrine activity.This has prompted numerous studies,to investigate the therapeutic potential of their secretome in general,and specifically their extracellular vesicles(EV).The latter contain proteins,lipids,nucleic acids,and other metabolites,which can cause physiological changes when released into recipient cells.Interestingly,contents of EV can be modulated by preconditioning MSC under different culture conditions.Among them,exposure to hypoxia stands out;these cells respond by activating hypoxia-inducible factor(HIF)at low O_(2) concentrations.HIF has direct and indirect pleiotropic effects,modulating expression of hundreds of genes involved in processes such as inflammation,migration,proliferation,differentiation,angiogenesis,metabolism,and cell apoptosis.Expression of these genes is reflected in the contents of secreted EV.Interestingly,numerous studies show that MSC-derived EV conditioned under hypoxia have a higher regenerative capacity than those obtained under normoxia.In this review,we show the implications of hypoxia responses in relation to tissue regeneration.In addition,hypoxia preconditioning of MSC is being evaluated as a very attractive strategy for isolation of EV,with a high potential for clinical use in regenerative medicine that can be applied to different pathologies.
基金supported by the Biomedical Research Networking Center on Frailty and Healthy Aging (CIBERFES)by European Regional Development Fund (FEDER) funds from the European Union (CB16/10/00477,CB16/10/00456, and CB16/10/00464)+4 种基金further funded by grants from the government of Castilla-La Mancha (PI2010/020Institute of Health Sciences,03031-00)the Spanish government (Spanish Ministry of Economy and Competitiveness (Ministerio de Economia y Competitividad)Institute of Health Carlos Ⅲ (Instituto de Salud Carlos Ⅲ),PI10/01532, PI031558,PI 11/01068)by European grants (Seventh Framework Programme:FRAILOMIC FP7-305483-2)。
文摘Purpose:This study aimed to examine the associations of accelerometer-derived steps volume and intensity with hospitalizations and all-cause mortality in older adults.Methods:This prospective cohort study involved 768 community-dwelling Spanish older adults(78.8±4.9 years,mean±SD;53.9% females)from the Toledo Study for Healthy Aging(2012-2017).The number of steps per day and step cadence(steps/min) were derived from a hip-mounted accelerometer worn for at least 4 days at baseline.Participants were followed-up over a mean period of 3.1 years for hospitalization and 5.7 years for all-cause mortality.Cox proportional hazards regression models were used to estimate the individual and joint associations between daily steps and stepping intensity with hospitalizations and all-cause mortality.Results:Included participants walked 5835± 3445 steps/day with an intensity of 7.3± 4.1 steps/min.After adjusting for age,sex,body mass index(BMI),education,income,marital status and comorbidities,higher step count(hazard ratio(HR)=0.95,95% confidence interval(95%CI:0.90-1.00,and HR=0.87,95%CI:0.81-0.95 per additional 1000 steps) and higher step intensity(HR=0.95,95%CI:0.91-0.99,and HR=0.89,95%CI:0.84-0.95 per each additional step/min) were associated with fewer hospitalizations and all-cause mortality risk,respectively.Compared to the group having low step volume and intensity,individuals in the group having high step volume and intensity had a lower risk of hospitalization(HR=0.72,95%CI:0.52-0.98) and all-cause mortality(HR=0.60,95%CI:0.37-0.98).Conclusion:Among older adults,both high step volume and step intensity were significantly associated with lower hospitalization and all-cause mortality risk.Increasing step volume and intensity may benefit older people.
基金supported by the funding from the Spanish Society of Cardiology
文摘Background Elderly patients with non-ST-segment elevation acute coronary syndromes(NSTE-ACS)may present delirium but its clinical relevance is unknown.This study aimed at detennining the clinical associated factors,and prognostic implications of delirium in old-aged patients admitted for NSTE-ACS.Methods LONGEVO-SCA is a prospective multicenter registry including unselected patients with NSTE-ACS aged>80 years.Clinical variables and a complete geriatric evaluation were assessed during hospitalization.The association between delirium and 6-month mortality was assessed by a Cox regression model weighted for a propensity score including the potential confounding variables.We also analysed its association with 6-month bleeding and cognitive or functional decline.Results Among 527 patients included,thirty-seven(7%)patients presented delirium during the hospitalization.Delirium was more frequent in patients with dementia or depression and in those from nursing homes(27.0%vs.3.1%,24.3%vs.11.6%,and 11.1%V5.2.2%,respectively;all P<0.05).Delirium was significantly associated with in-hospital infections(27.0%vs.5.3%,P<0.001)and usage of diuretics(70.3%vs.49.8%,P=0.02).Patients with delirium had longer hospitalizations[median 8.5(5.5-14)vs.6.0(4.0-10)days,P=0.02]and higher incidence of 6-month bleeding and mortality(32.3%vs.10.0%and 24.3%vs.10.8%,respectively;both P<0.05)but similar cognitive or functional decline.Delirium was independently associated with 6-month mortality(HR=1.47,95%CI:1.02-2.13,P=0.04)and 6-month bleeding events(OR=2.87;95%CI:1.98-4」6,P<0.01).Conclusions In-hospital delirium in elderly patients with NSTE-ACS is associated with some preventable risk factors and it is an independent predictor of 6-month mortality.
文摘Non-alcoholic fatty liver disease(NAFLD)prevalence has increased drastically in recent decades,affecting up to 25%of the world’s population.NAFLD is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis,which can progress to fibrosis.Several molecular and metabolic changes are required for the hepatocyte to finally vary its function;hence a“multiple hit”hypothesis seems a more accurate proposal.Previous studies and current knowledge suggest that in most cases,NAFLD initiates and progresses through most of nine hallmarks of the disease,although the triggers and mechanisms for these can vary widely.The use of animal models remains crucial for understanding the disease and for developing tools based on biological knowledge.Among certain requirements to be met,a good model must imitate certain aspects of the human NAFLD disorder,be reliable and reproducible,have low mortality,and be compatible with a simple and feasible method.Metabolism studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the disease.Metabolomics seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological understanding.In this review,we provide a brief introduction to NAFLD hallmarks,the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD.
基金Supported by grants "Fragilidad y Envejecimiento Saludable"(CIBERFES)of "Instituto de Salud Carlos Ⅲ"(ISCⅢ)No.PI15/01857,PI18/01659 and CIBER
文摘Extra virgin olive oil is characterized by its high content of unsaturated fatty acid residues in triglycerides,mainly oleic acid,and the presence of bioactive and antioxidant compounds.Its consumption is associated with lower risk of suffering chronic diseases and unwanted processes linked to aging,due to the antioxidant capacity and capability of its components to modulate cellular signaling pathways.Consumption of olive oil can alter the physiology of mesenchymal stem cells(MSCs).This may explain part of the healthy effects of olive oil consumption,such as prevention of unwanted aging processes.To date,there are no specific studies on the action of olive oil on MSCs,but effects of many components of such food on cell viability and differentiation have been evaluated.The objective of this article is to review existing literature on how different compounds of extra virgin olive oil,including residues of fatty acids,vitamins,squalene,triterpenes,pigments and phenols,affect MSC maintenance and differentiation,in order to provide a better understanding of the healthy effects of this food.Interestingly,most studies have shown a positive effect of these compounds on MSCs.The collective findings support the hypothesis that at least part of the beneficial effects of extra virgin olive oil consumption on health may be mediated by its effects on MSCs.
基金part of the project entitled Body Adiposity Index and Biomarkers of Endothelial and Cardiovascular Health in Adults,which was funded by the Centre for Studies on Measurement of Physical Activity,School of Medicine and Health Sciences,Universidad del Rosario(Code N°FIUR DNBG001)Universidad de Boyacá(Code N°RECT 60)。
文摘Background: Evidence shows an association between grip strength and health;however, grip strength cut-offs for the detection of metabolic syndrome(MetS) in Latin American populations are scarce. The purpose of this study was to determine cut-offs of normalized grip strength(NGS)for the detection of MetS in a large nonrepresentative sample of a collegiate student population from Colombia.Methods: A total of 1795 volunteers(61.4% female;age = 20.68 ± 3.10 years, mean ± SD), ranging between 18 and 30 years of age participated in the study. Strength was estimated using a handheld dynamometer and normalized to body mass(handgrip strength(kg)/body mass(kg)). Anthropometrics, serum lipids indices, blood pressure, and fasting plasma glucose were measured. Body composition was measured by bioelectrical impedance analysis. MetS was defined as including ≥3 of the 5 metabolic abnormalities according to the International Diabetes Federation definition. A metabolic risk score was computed from the following components: waist circumference, triglycerides, high-density lipoprotein cholesterol, glucose, and systolic and diastolic blood pressure.Results: Receiver operating curve analysis showed significant discriminatory accuracy of NGS in identifying the thresholds and risk categories.Lower strength was associated with increased prevalence of MetS. In males, weak, intermediate, and strong NGS values at these points were<0.466, 0.466-0.615, >0.615, respectively. In females, these cut-off points were <0.332, 0.332-0.437, >0.437, respectively.Conclusion: Our sex-specific cut-offs of NGS could be incorporated into a clinical setting for identifying college students at cardiometabolic disease risk.
基金funded by the University of Castilla-La Mancha (MS2021)
文摘Dear Editor,We have read with interest the commentary by McAvoy and Tudor-Locke on our article entitled "Association of accelerometer-derived step volume and intensity with ho spitalizations and mortality in older adults:A prospective cohort study". The authors expressed some concerns about our methodology used to define accelerometer-derived step intensity and the analytical approach applied in our study.
文摘Objectives To assess the effects of an exercise training program combining power-oriented resistance training(RT)and high-intensity interval training(HIIT)on metabolic syndrome(MetS)markers in older people with COPD.Methods Twenty-nine older people(66–90 years old)with COPD were randomly assigned to 12 weeks of exercise training(ET;power-oriented RT+HIIT)or a control group(CON).Waist circumference,diastolic(DBP)and systolic blood pressure(SBP),and serum fasting glucose,triglycerides and HDL cholesterol levels were assessed at baseline and after 12 weeks.Linear mixed-effects models were used to assess the effects of the intervention,and data were reported as mean and 95%confidence interval values.Results Waist circumference increased in the CT group,but not in the ET group(2.0[0.2,3.7]vs.1.0[−1.3,3.2]cm,respectively).No changes in fasting glucose(−4.1[−10.3,2.1]vs.−1.0[−8.7,6.7]mg dL−1),triglycerides(3.9[−13.4,21.3]vs.−13.9[−35.6,7.7]mg dL−1)or HDL cholesterol(1.0[−3.4,5.4]vs.2.9[−2.6,8.4]mg dL−1)were found in the CT or ET group,respectively.The ET group exhibited decreased DBP(−5.2[−9.5,−0.8]mmHg)and SBP(−2.7[−22.7,−2.7]mmHg),while no changes were found in the CT group(0.3[−3.2,3.7]and−3.5[−11.4,4.5]mmHg).MetS z-score declined in ET but remained unchanged in CT(−0.88[−1.74,−0.03]vs.0.07[−0.62,0.76],respectively).Conclusions A 12-week exercise training program led to a reduction in blood pressure and MetS z-score in older people with COPD.
基金Supported by Government of Extremadura GAEDAF Research Group,No.GR18003Ministerio de Educación,Cultura y Deporte,No.FPU15/00452and Instituto de Salud Carlos III,No.PI15/01857 and No.PI18/01659.
文摘BACKGROUND Mesenchymal stem cells(MSC)of bone marrow are the progenitor of osteoblasts and adipocytes.MSC tend to differentiate into adipocytes,instead of osteoblasts,with aging.This favors the loss of bone mass and development of osteoporosis.Hypoxia induces hypoxia inducible factor 1αgene encoding transcription factor,which regulates the expression of genes related to energy metabolism and angiogenesis.That allows a better adaptation to low O2 conditions.Sustained hypoxia has negative effects on bone metabolism,favoring bone resorption.Yet,surprisingly,cyclic hypoxia(CH),short times of hypoxia followed by long times in normoxia,can modulate MSC differentiation and improve bone health in aging.AIM To evaluate the CH effect on MSC differentiation,and whether it improves bone mineral density in elderly.METHODS MSC cultures were induced to differentiate into osteoblasts or adipocytes,in CH(3%O2 for 1,2 or 4 h,4 d a week).Extracellular-matrix mineralization and lipid-droplet formation were studied in MSC induced to differentiate into osteoblast or adipocytes,respectively.In addition,gene expression of marker genes,for osteogenesis or adipogenesis,have been quantified by quantitative real time polymerase chain reaction.The in vivo studies with elderly(>75 years old;n=10)were carried out in a hypoxia chamber,simulating an altitude of 2500 m above sea level,or in normoxia,for 18 wk(36 CH sessions of 16 min each).Percentages of fat mass and bone mineral density from whole body,trunk and right proximal femur(femoral,femoral neck and trochanter)were assessed,using dual-energy X-ray absorptiometry.RESULTS CH(4 h of hypoxic exposure)inhibited extracellular matrix mineralization and lipid-droplet formation in MSC induced to differentiate into osteoblasts or adipocytes,respectively.However,both parameters were not significantly affected by the other shorter hypoxia times assessed.The longest periods of hypoxia downregulated the expression of genes related to extracellular matrix formation,in MSC induced to differentiate into osteoblasts.Interestingly,osteocalcin(associated to energy metabolism)was upregulated.Vascular endothelial growth factor an expression and low-density lipoprotein receptor related protein 5/6/dickkopf Wnt signaling pathway inhibitor 1(associated to Wnt/β-catenin pathway activation)increased in osteoblasts.Yet,they decreased in adipocytes after CH treatments,mainly with the longest hypoxia times.However,the same CH treatments increased the osteoprotegerin/receptor activator for nuclear factor kappa B ligand ratio in both cell types.An increase in total bone mineral density was observed in elderly people exposed to CH,but not in specific regions.The percentage of fat did not vary between groups.CONCLUSION CH may have positive effects on bone health in the elderly,due to its possible inhibitory effect on bone resorption,by increasing the osteoprotegerin/receptor activator for nuclear factor kappa B ligand ratio.
基金funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud CarlosⅢ(PI13/01393)by the Retos de la Sociedad program(DEP2016-79512-R)+7 种基金European Regional Development Funds(ERDF)the Spanish Ministry of Education(FPU13/04365 and FPU19/01609)the Fundación Iberoamericana de Nutrición(FINUT)the Redes Temáticas de Investigación Cooperativa RETIC(Red SAMID RD16/0022)the Astra Zeneca Health Care Foundationthe University of Granada Plan Propio de Investigación 2016-Excellence actions:Unit of Excellence on Exercise and Health(UCEES)-and Plan Propio de Investigación 2018-the Programa Contratos-Puente and Contratos Perfeccionamiento de Doctoresthe Junta de Andalucía,Consejería de Conocimiento,Investigacióny Universidades(ERDF,ref.SOMM17/6107/UGR)the Fundación Alfonso Martín Escudero(grant awarded to GSD)。
文摘Purpose:The present work examines the associations of dietary habits,sedentarism,physical activity(PA)levels and sleep habits,with thyroid function in young euthyroid adults.Methods:A total of 105 young euthyroid adults participated in this cross-sectional study.Thyroid function was determined in fasting conditions(>6 h).Dietary habits were measured by a food frequency questionnaire and three non-consecutive 24 h recalls,and different dietary intake and patterns were then estimated.The time spent in sedentary,PA levels and sleep habits were objectively measured using a wrist-worn accelerometer.Results:Energy and carbohydrate intake were positively associated with thyroid stimulating hormone(TSH)(β=0.222;R^(2)=0.102;P=0.022 andβ=0.425;R^(2)=0.129;P=0.007,respectively)whereas fat intake was negatively associated with TSH(β=-0.428;R^(2)=0.137;P=0.004).Energy intake was also positively associated with free triiodothyronine(β=0.277;R^(2)=0.137;P=0.004).Further,adherence to the Mediterranean diet was negatively related to TSH and free thyroxine(FT4)(β=-0.221;R^(2)=0.113;P=0.020 andβ=-0.268;R^(2)=0.071;P=0.007,respectively).Vigorous-intensity and overall PA were negatively associated with FT4(β=-0.227;R^(2)=0.052;P=0.022 andβ=-0.204;R^(2)=0.042;P=0.041,respectively).In contrast,no associations were found between sleep parameters and thyroid function.Conclusions:Lifestyle factors such as dietary intake and PA levels seems to be related to thyroid function even in young euthyroid adults.
基金supported by the National Natural Science Foundation of China(82070422,82200330)the China Postdoctoral Science Foundation(2023T160526 and 2022M722571)+2 种基金the Research Plan Project of Shaanxi Institute of Basic Science(22JHQ053)the High-end Foreign Expert Introduction Program of National Science and Technology(G2022040014L)the Qinchuangyuan Traditional Chinese Medicine Innovation Research and Development Transformation Project(2022-QCYZH-036).
文摘Nuclear receptor subfamily 1,group D,member 1(NR1D1,also known as REV-ERBα)belongs to the nuclear receptor(NR)family,and is a heme-binding component of the circadian clock that consolidates circadian oscillators.In addition to repressing the transcription of multiple clock genes associated with circadian rhythms,NR1D1 has a wide range of downstream target genes that are intimately involved in many physiopathological processes,including autophagy,immunity,inflammation,metabolism,and aging in multiple organs.This review focuses on the pivotal role of NR1D1 as a key transcription factor in the gene regulatory network,with particular emphasis on the milestones of the latest discoveries of NR1D1 ligands.NR1D1 is considered as a promising drug target for treating diverse diseases and may contribute to research on innovative biomarkers and therapeutic targets for organ injury-related diseases.Further research on NR1D1 ligands in prospective human trials may pave the way for their clinical application in many organ injury-related disorders.
基金supported by Spanish Ministry of Science and Innovation(MCIN/AEI/10.13039/501100011033/FEDER,UE)grants PID2021-123141OB-I00 to J.J.L.and PID2022-138813OB-I00 to J.P.B.
文摘In a recent study published in Cell,Woo et al.1 investigated the role of the immunoproteasome and the metabolic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3)in neurons in the context of multiple sclerosis(MS)-related IFNγsignaling,finding new therapeutic targets for neurodegeneration in MS and possibly other related neuroinflammatory neurodegenerative disorders.
文摘The SARS-CoV-2-caused COVID-19 pandemic has resulted in a devastating threat to human society in terms of health,economy,and lifestyle.Although the virus usually first invades and infects the lung and respiratory track tissue,in extreme cases,almost all major organs in the body are now known to be negatively impacted often leading to severe systemic failure in some people.Unfortunately,there is currently no effective treatment for this disease.Pre-existing pathological conditions or comorbidities such as age are a major reason for premature death and increased morbidity and mortality.The immobilization due to hospitalization and bed rest and the physical inactivity due to sustained quarantine and social distancing can downregulate the ability of organs systems to resist to viral infection and increase the risk of damage to the immune,respiratory,cardiovascular,musculoskeletal systems and the brain.The cellular mechanisms and danger of this“second wave”effect of COVID-19 to the human body,along with the effects of aging,proper nutrition,and regular physical activity,are reviewed in this article.
文摘Cocoa is the main component of chocolate.It is widely accepted that cocoa quality largely depends on the processing,especially the fermentation step.Traditionally,fermentation takes place spontaneously by the endogenous microbiota;however,the process can lead to poor quality and heterogeneity of the final product.In this study,we evaluated the influence of the starter culture on the profile of volatiles during fermentation of commercial volumes of Mexican cocoa.Volatiles were also analyzed in post-fermented cocoa samples obtained after drying,roasting,and conching.Our results revealed a most desirable volatile profile in cocoa fermented with starter culture,mainly due to the higher relative content of alcohols(40%)and aldehydes(3.5%),but also due to a lower acidity(<1%)as compared to endogenous fermentation(acids,65%;alcohols,2%;and aldehydes<0.5%).Additionally,it is remarkable,the higher content of pyrazines in the inoculated samples after processing.
基金supported by the following grants:Instituto de Salud Carlos III and co-funded by FEDER[grant number PIE15/00013]SAF2016-75508-R from the Spanish Ministry of Education and Science(MEC),CB16/10/00435(CIBERFES),PROMETEOII2014/056 from“Conselleria,de Sanitat de la Generalitat Valenciana(GV/2018/118)EU Funded CM1001 and FRAILOMIC-HEALTH.2012.2.1.1-2,ADVANTAGE-724099 Join Action(HP-JA)3rd EU Health Programme and DIALBFRAIL-LATAM(825546 H2020-SC1-BHC).A.S-P was funded with a FPU grant from the Spanish MECD.
文摘Demographic aging is one of the most serious challenges facing our society.Although we live longer,we do not live better because it is considered that approximately 16–20%of our life is spent in late-life morbidity.Older people have the greatest risk of developing frailty increasing the risk of presenting various adverse health events such as low quality of life,disability,hospitalization and even death.Frail men and women over 65 years old have lower muscle quality and muscle mass and higher percentage of body fat than non-frail people of the same age.In this review we will address the main physiological changes in the muscular and nervous system associated to aging.More specifically we will review the changes in muscle mass,quality,and strength relating them with the decrease in capillarization and muscular oxidative capacity as well as with the alterations in protein synthesis in the muscle with aging.The last section of the manuscript will be devoted to the animal models of frailty and the indexes developed to measure frailty in these models.We will finally address the importance of exercise training as an intervention to delay or even reverse frailty.
