Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortal...Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortality.Mitochondrial dysfunction,a major hallmark of aging,plays a central role in the loss of muscle mass and strength observed in frailty and sarcopenia.With age,mitochondrial quality control processes,including biogenesis,mitophagy,and dynamics,become dysregulated,impairing energy metabolism and muscle homeostasis.Mitochondrial dysfunction correlates with clinical biomarkers of sarcopenia and frailty,such as the decrease in walking speed and muscle strength,making it a therapeutic target for mitohormesis-based strategies aimed at preserving functional capacity.Mitohormetic agents induce reversible mitochondrial stress,triggering adaptive responses that enhance function.Among these interventions,physical exercise,particularly endurance and resistance training(RT),has been reported to be among the most effective,as it may modulate mitochondrial biogenesis,dynamics,and mitophagy through increases in proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)and mitochondrial transcription factor A(TFAM)expression,mitochondrial deoxyribonucleic acid(mtDNA)copy number,and mitochondrial content.Chronic RT can also elevate fusion and fission markers,potentially as a compensatory mechanism to mitigate mitochondrial damage.Apart from exercise,mitohormetic compounds such as harmol and piceid are emerging as promising supplements in the aging field.By modulating mitochondrial bioenergetics and dynamics,they may complement lifestyle-based interventions to improve mitochondrial fitness and extend health span.展开更多
Background:Low relative sit-to-stand(STS)power has emerged as a critical predictor of adverse health outcomes,such as frailty and disability,in older adults.However,its impact on falls,fractures,hospitalizations,and a...Background:Low relative sit-to-stand(STS)power has emerged as a critical predictor of adverse health outcomes,such as frailty and disability,in older adults.However,its impact on falls,fractures,hospitalizations,and all-cause mortality remains unclear.Therefore,this longitudinal study aimed to investigate the potential associations between low relative STS power and these adverse health outcomes in older adults.Methods:A total of 1876 older adults(aged≥65 years,56.4%women)were included from the Toledo Study for Healthy Aging.Relative STS power was assessed using the 30-s STS test and the Alcazar equation.Participants were categorized as having low relative STS power based on previously established cut-off points(2.53 W/kg for men and 2.01 W/kg for women).Falls and fractures(hip and all-type)within the previous year were recorded.Hospitalizations and all-cause mortality were obtained during a follow-up of 6.8±3.1 years(mean±SD;median=7.8 years;interquartile range:3.9-10.1 years)and 9.7±3.5 years(median=10.9 years;interquartile range:8.2-12.5 years),respectively.Generalized linear mixed models,binary logistic regression,and proportional hazards regression adjusted for age,educational level,and comorbidities were used.Results:In men,low relative STS power was significantly associated with an increased likelihood of history of falls(odds ratio(OR)=1.73,95%confidence interval(95%CI):1.08-2.75,p=0.022)and all-type fractures(OR=1.86,95%CI:1.21-2.84,p=0.004)in the previous year.In women,low relative STS power was associated with a higher probability of hip fractures within the previous year(OR=3.25,95%CI:1.07-9.86,p=0.038).Low relative STS power predicted hospitalizations in women(hazard ratio(HR)=1.29,95%CI:1.06-1.58,p=0.012)and longer hospital stays in both men(p=0.020)and women(p=0.033).Low relative STS power significantly increased all-cause mortality in both men(HR=1.57,95%CI:1.26-1.97,p<0.001)and women(HR=2.04,95%CI:1.51-2.74,p<0.001).Conclusion:Low relative STS power was associated with history of hip fractures in women,whereas in men it was associated with history of falls and all-type fractures.Low relative STS power predicted hospitalizations in women but not in men.In both men and women,low relative STS power was associated with longer hospital stays and increased risk of all-cause mortality.展开更多
In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflamma...In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.展开更多
Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level...Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level.However,the recently described multiple cell differentiation dynamics suggest that some bone cells are indeed the progeny of cartilage cells,or chondrocyte-derived osteoblasts.We hypothesized that the cartilage-to-bone phenotype transition is triggered by specific molecular events.First,the process was assessed in mouse bone tissue,and then,it was mimicked using in vivo cell implantation and in vitro serial differentiation protocols.Data indicates that cartilage cells transition to bone cell phenotype during postnatal physiological bone formation.This process can be reproduced using cartilage precursor cells coupled to specific implantation procedures or differentiation protocols.Gene expression profiling reveals that NOTCH,BMP and MAPK signaling pathways are relevant at the phenotype-switch,while the transcription factors Mesp1,Alx1,Grhl3 and Hmx3 are the feasible driver genes for chondrocyte-derived osteoblasts formation.Altogether,this report shows that endochondral ossification can be modeled using primary cell cultures and data indicate that this process is regulated by specific molecular events,previously described at skeleton morphogenesis during embryo development,and from now on also linkable to postnatal bone development and regeneration processes.展开更多
The purpose of this article is to provide a follow-up review of the impact of the SARS-CoV-2 Disease or Coronavirus Disease 2019(COVID-19)pandemic on human health and the role of physical activity(PA)during the 5-year...The purpose of this article is to provide a follow-up review of the impact of the SARS-CoV-2 Disease or Coronavirus Disease 2019(COVID-19)pandemic on human health and the role of physical activity(PA)during the 5-year pandemic.We aim to cover the immune system,the cardiopulmonary system,the musculoskeletal system,and the central nervous system(brain function),particularly among older adults,college students,and individuals with post-acute sequelae of COVID-19(Long-COVID).The COVID-19 pandemic has given us many lessons,learned from the death of six million lives and tremendous disturbance to human life.First,we need to continue to investigate cellular and molecular mechanisms that mediate various organistic failures resulting from the viral infection.Such investigations are the only way to completely understand the etiology of the diseases and to develop new drugs and vaccines.The molecular pathways that transmit the signals of viral infection to each organ system are different requiring both basic and clinical research.Available evidence suggests that mitochondrial dysfunction,reduced microcirculation and latent immune activation play a major role,eventually impairing cardiovascular tolerance and peripheral bioenergetics.Second,the COVID-19 pandemic has manifested major disturbances to human lifestyles with reduced PA and exercise standing out as a major factor.Conversely,physical inactivity due to social confinement and mental/psychological stresses has been clearly linked to intensified pathogenic symptoms and amplification of adverse effects on multiple physiological systems.If not intervened,this interaction can lead to Long-COVID,a dangerous futile circle to cause systemic failure.Finally,the COVID-19 pandemic has exerted differential impacts on different populations.Thus,the strategy to develop and conduct to cope with the negativity of pandemic needs to be specific,flexible and tailored to fit different patient populations.展开更多
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
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
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
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
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
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
基金Instituto de Salud CarlosⅢCB16/10/00435(CIBERFES)(PID2022-142470OB-I00)from the Spanish Ministry of Innovation and Science+3 种基金PROMETEO(CIPROM/2022/56)de"Consellería de Educación,Universidades,y Empleo de la Generalitat Valenciana"EU Funded H2020-DIABFRAIL-LATAM(Ref:825546)Red EXERNET-RED DE EJERCICIO FISICO Y SALUD(RED2022-134800-T)Agencia Estatal de Investigacion(Ministerio de Ciencias e Innovación)funded by Generalitat Valenciana and co-financed with FEDER funds(OP FEDER of Comunitat Valenciana 2014–2020).A.G-G(FPU22/02539)and S.S-R(PREP2022-000563)received a predoctoral grant financed by the Spanish Ministry of Universities.
文摘Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortality.Mitochondrial dysfunction,a major hallmark of aging,plays a central role in the loss of muscle mass and strength observed in frailty and sarcopenia.With age,mitochondrial quality control processes,including biogenesis,mitophagy,and dynamics,become dysregulated,impairing energy metabolism and muscle homeostasis.Mitochondrial dysfunction correlates with clinical biomarkers of sarcopenia and frailty,such as the decrease in walking speed and muscle strength,making it a therapeutic target for mitohormesis-based strategies aimed at preserving functional capacity.Mitohormetic agents induce reversible mitochondrial stress,triggering adaptive responses that enhance function.Among these interventions,physical exercise,particularly endurance and resistance training(RT),has been reported to be among the most effective,as it may modulate mitochondrial biogenesis,dynamics,and mitophagy through increases in proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)and mitochondrial transcription factor A(TFAM)expression,mitochondrial deoxyribonucleic acid(mtDNA)copy number,and mitochondrial content.Chronic RT can also elevate fusion and fission markers,potentially as a compensatory mechanism to mitigate mitochondrial damage.Apart from exercise,mitohormetic compounds such as harmol and piceid are emerging as promising supplements in the aging field.By modulating mitochondrial bioenergetics and dynamics,they may complement lifestyle-based interventions to improve mitochondrial fitness and extend health span.
基金supported by Centro de Investigaci on Biom edica en Red Fragilidad y Envejecimiento Saludable(CIBERFES)(Grant Nos.CB16/10/00477,CB16/10/00456,and CB16/10/00464)Plan Propio de Investigaci on of the University of Castilla-La Mancha,and Fondo Europeo de Desarrollo Regional(FEDER)funds from the European Union(Grant No.2022-GRIN-34296)+3 种基金further funded by grants from the Instituto de Salud Carlos III(Grant Nos.PI031558,PI07/90637,PI07/90306,RD 06/0013,and PI18/00972)the Government of Castilla-La Mancha(Grant Nos.03031 and SBPLY/19/180501/000312)Red EXERNETRED DE EJERCICIO FISICO Y SALUD:RED2022-134800T from the Spanish Ministry of Innovation and Sciencesupported by a research grant from the University of Castilla-La Mancha(Programa Investigo,Grant No.2024INVGO-12359)。
文摘Background:Low relative sit-to-stand(STS)power has emerged as a critical predictor of adverse health outcomes,such as frailty and disability,in older adults.However,its impact on falls,fractures,hospitalizations,and all-cause mortality remains unclear.Therefore,this longitudinal study aimed to investigate the potential associations between low relative STS power and these adverse health outcomes in older adults.Methods:A total of 1876 older adults(aged≥65 years,56.4%women)were included from the Toledo Study for Healthy Aging.Relative STS power was assessed using the 30-s STS test and the Alcazar equation.Participants were categorized as having low relative STS power based on previously established cut-off points(2.53 W/kg for men and 2.01 W/kg for women).Falls and fractures(hip and all-type)within the previous year were recorded.Hospitalizations and all-cause mortality were obtained during a follow-up of 6.8±3.1 years(mean±SD;median=7.8 years;interquartile range:3.9-10.1 years)and 9.7±3.5 years(median=10.9 years;interquartile range:8.2-12.5 years),respectively.Generalized linear mixed models,binary logistic regression,and proportional hazards regression adjusted for age,educational level,and comorbidities were used.Results:In men,low relative STS power was significantly associated with an increased likelihood of history of falls(odds ratio(OR)=1.73,95%confidence interval(95%CI):1.08-2.75,p=0.022)and all-type fractures(OR=1.86,95%CI:1.21-2.84,p=0.004)in the previous year.In women,low relative STS power was associated with a higher probability of hip fractures within the previous year(OR=3.25,95%CI:1.07-9.86,p=0.038).Low relative STS power predicted hospitalizations in women(hazard ratio(HR)=1.29,95%CI:1.06-1.58,p=0.012)and longer hospital stays in both men(p=0.020)and women(p=0.033).Low relative STS power significantly increased all-cause mortality in both men(HR=1.57,95%CI:1.26-1.97,p<0.001)and women(HR=2.04,95%CI:1.51-2.74,p<0.001).Conclusion:Low relative STS power was associated with history of hip fractures in women,whereas in men it was associated with history of falls and all-type fractures.Low relative STS power predicted hospitalizations in women but not in men.In both men and women,low relative STS power was associated with longer hospital stays and increased risk of all-cause mortality.
基金part of the EU consortium DCog Plast ‘Diet Cognition and Plasticity” funded by the Joint Programming Initiative “A Health Diet for a Healthy Life”(JPI-HDHL) via the BMWFW (BMWFW-10.420/0009-WF/V/3c/2015 and the Medical Research Council UK:MR/N030087/1)(to LA and ST)supported by the PMU-FFF Research Fund (A-16/01/019-AIG)+9 种基金BA by the PMU-Research and Innovation Fund (PMU-RIF)(project 2023-PRE-008-Altendorfer)supported by the Center for Urban Mental Healthby Alzheimer Nederlandthe Zon MW Program Mechanisms Of DEMentia (MODEM)by the Gravitation program iCNS of the Dutch Research Council (NWO)supported by Grant PID2020-114921RB-C21Maria de Maeztu Unit of Excellence grant CEX2021-001234-M funded by MCIU/AEI/and CIBERFESCB16/10/00269, from the Instituto de Salud Carlos III all of them by “ERDF A way of making Europe”the Generalitat de Catalunya’s Agency AGAUR of 2021SGR00687ICREA Award
文摘In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.
基金funded by Grants PID2021-127191OB-I00,RTI2018-101708-A-I00,PRE2018-084542 and PRE2022-102680 funded by MCIN/AEI/10.13039/501100011033 and by“ERDF A way of making Europe”Grant RYC2018-025502-I is funded by MCIN/AEI/10.13039/501100011033 and by“ESF Investing in your future”+1 种基金Grant MDM-20170720 Maria de Maeztu Units of Excellence Program funded by the Spanish State Research Agencysupported by Instituto de Salud CarlosⅢ,Infrastructure of Precision Medicine associated with Science and Technology(IMPaCT)of the Strategic Action in Health(iDATA-MP)。
文摘Endochondral ossification is a physiological process involving a sequential formation of cartilage and bone tissues.Classically,cartilage and bone formation have been considered independent processes at cellular level.However,the recently described multiple cell differentiation dynamics suggest that some bone cells are indeed the progeny of cartilage cells,or chondrocyte-derived osteoblasts.We hypothesized that the cartilage-to-bone phenotype transition is triggered by specific molecular events.First,the process was assessed in mouse bone tissue,and then,it was mimicked using in vivo cell implantation and in vitro serial differentiation protocols.Data indicates that cartilage cells transition to bone cell phenotype during postnatal physiological bone formation.This process can be reproduced using cartilage precursor cells coupled to specific implantation procedures or differentiation protocols.Gene expression profiling reveals that NOTCH,BMP and MAPK signaling pathways are relevant at the phenotype-switch,while the transcription factors Mesp1,Alx1,Grhl3 and Hmx3 are the feasible driver genes for chondrocyte-derived osteoblasts formation.Altogether,this report shows that endochondral ossification can be modeled using primary cell cultures and data indicate that this process is regulated by specific molecular events,previously described at skeleton morphogenesis during embryo development,and from now on also linkable to postnatal bone development and regeneration processes.
文摘The purpose of this article is to provide a follow-up review of the impact of the SARS-CoV-2 Disease or Coronavirus Disease 2019(COVID-19)pandemic on human health and the role of physical activity(PA)during the 5-year pandemic.We aim to cover the immune system,the cardiopulmonary system,the musculoskeletal system,and the central nervous system(brain function),particularly among older adults,college students,and individuals with post-acute sequelae of COVID-19(Long-COVID).The COVID-19 pandemic has given us many lessons,learned from the death of six million lives and tremendous disturbance to human life.First,we need to continue to investigate cellular and molecular mechanisms that mediate various organistic failures resulting from the viral infection.Such investigations are the only way to completely understand the etiology of the diseases and to develop new drugs and vaccines.The molecular pathways that transmit the signals of viral infection to each organ system are different requiring both basic and clinical research.Available evidence suggests that mitochondrial dysfunction,reduced microcirculation and latent immune activation play a major role,eventually impairing cardiovascular tolerance and peripheral bioenergetics.Second,the COVID-19 pandemic has manifested major disturbances to human lifestyles with reduced PA and exercise standing out as a major factor.Conversely,physical inactivity due to social confinement and mental/psychological stresses has been clearly linked to intensified pathogenic symptoms and amplification of adverse effects on multiple physiological systems.If not intervened,this interaction can lead to Long-COVID,a dangerous futile circle to cause systemic failure.Finally,the COVID-19 pandemic has exerted differential impacts on different populations.Thus,the strategy to develop and conduct to cope with the negativity of pandemic needs to be specific,flexible and tailored to fit different patient populations.
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.
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.
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 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.
