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1.
Artigo em Inglês | MEDLINE | ID: mdl-31912990

RESUMO

BACKGROUND: There has been limited longitudinal assessment of the relationship between moderate-to-vigorous physical activity (MVPA) and sedentary behaviour (SB) with frailty, and no studies have explored the possibility of reverse causality. This study aimed to determine the potential bidirectionality of the relationship between accelerometer-assessed MVPA, SB, and frailty over time in older adults. METHODS: Participants were from the Toledo Study for Healthy Aging. We analysed 186 older people aged 67 to 90 (76.7 ± 3.9; 52.7% female participants) over a 4-year period. Time spent in SB and MVPA was assessed by accelerometry. Frailty Trait Scale was used to determine frailty levels. A cross-lagged panel model design was used to test the reciprocal relationships between MVPA/SB and frailty. RESULTS: Frailty Trait Scale score changed from 35.4 to 43.8 points between the two times (P < 0.05). We also found a reduction of 7 min/day in the time spent on MVPA (P < 0.05), and participants tended to spend more time on SB (P = 0.076). Our analyses revealed that lower levels of initial MVPA predicted higher levels of later frailty [std. ß = -0.126; confidence interval (CI) = -0.231, -0.021; P < 0.05], whereas initial spent time on SB did not predict later frailty (std. ß = -0.049; CI = -0.185, 0.087; P = 0.48). Conversely, an initial increased frailty status predicted higher levels of later SB (std. ß = 0.167; CI = 0.026, 0.307; P < 0.05) but not those of MVPA (std. ß = 0.071; CI = -0.033, 0.175; P = 0.18). CONCLUSIONS: Our observations suggest that the relationship between MVPA/SB and frailty is unidirectional: individuals who spent less time on MVPA at baseline are more likely to increase their frailty score, and individuals who are more frail are more likely to spent more time on SB at follow-up. Interventions and policies should aim to increase MVPA levels from earlier stages to promote successful aging.

2.
BMC Geriatr ; 19(1): 270, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615446

RESUMO

BACKGROUND: Physical activity and sedentary behaviour have been suggested to independently affect a number of health outcomes. To what extent different combinations of physical activity and sedentary behaviour may influence physical function and frailty outcomes in older adults is unknown. The aim of this study was to examine the combination of mutually exclusive categories of accelerometer-measured physical activity and sedentary time on physical function and frailty in older adults. METHODS: 771 older adults (54% women; 76.8 ± 4.9 years) from the Toledo Study for Healthy Aging participated in this cross-sectional study. Physical activity and sedentary time were measured by accelerometry. Physically active was defined as meeting current aerobic guidelines for older adults proposed by the World Health Organization. Low sedentary was defined as residing in the lowest quartile of the light physical activity-to-sedentary time ratio. Participants were then classified into one of four mutually exclusive movement patterns: (1) 'physically active & low sedentary', (2) 'physically active & high sedentary', (3) 'physically inactive & low sedentary', and (4) 'physically inactive & high sedentary'. The Short Physical Performance Battery was used to measure physical function and frailty was assessed using the Frailty Trait Scale. RESULTS: 'Physically active & low sedentary' and 'physically active & high sedentary' individuals had significantly higher levels of physical function (ß = 1.73 and ß = 1.30 respectively; all p < 0.001) and lower frailty (ß = - 13.96 and ß = - 8.71 respectively; all p < 0.001) compared to 'physically inactive & high sedentary' participants. Likewise, 'physically inactive & low sedentary' group had significantly lower frailty (ß = - 2.50; p = 0.05), but significance was not reached for physical function. CONCLUSIONS: We found a dose-response association of the different movement patterns analysed in this study with physical function and frailty. Meeting the physical activity guidelines was associated with the most beneficial physical function and frailty profiles in our sample. Among inactive people, more light intensity relative to sedentary time was associated with better frailty status. These results point out to the possibility of stepwise interventions (i.e. targeting less strenuous activities) to promote successful aging, particularly in inactive older adults.

3.
Gut ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530714

RESUMO

OBJECTIVE: Liver fibrosis constitutes a major health problem worldwide due to its rapidly increasing prevalence and the lack of specific and effective treatments. Growing evidence suggests that signalling through cytokine-activated Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways regulates liver fibrosis and regeneration. Rilpivirine (RPV) is a widely used anti-HIV drug not reported to produce hepatotoxicity. We aimed to describe the potential hepatoprotective effects of RPV in different models of chronic liver injury, focusing on JAK-STAT signalling regulation. DESIGN: The effects of RPV on hepatic steatosis, inflammation and fibrogenesis were studied in a nutritional mouse model of non-alcoholic fatty liver disease, carbon tetrachloride-induced fibrosis and bile duct ligation-induced fibrosis. Primary human hepatic stellate cells (hHSC) and human cell lines LX-2 and Hep3B were used to investigate the underlying molecular mechanisms. RESULTS: RPV exerted a clear anti-inflammatory and antifibrotic effect in all the in vivo models of liver injury employed, and enhanced STAT3-dependent proliferation in hepatocytes and apoptosis in HSC through selective STAT1 activation. These results were reproduced in vitro; RPV undermined STAT3 activation and triggered STAT1-mediated pathways and apoptosis in HSC. Interestingly, this selective pro-apoptotic effect completely disappeared when STAT1 was silenced. Conditioned medium experiments showed that HSC apoptosis activated STAT3 in hepatocytes in an interleukin-6-dependent mechanism. CONCLUSION: RPV ameliorates liver fibrosis through selective STAT1-dependent induction of apoptosis in HSC, which exert paracrinal effects in hepatocytes, thus promoting liver regeneration. RPV's actions may represent an effective strategy to treat chronic liver diseases of different aetiologies and help identify novel therapeutic targets.

4.
J Cachexia Sarcopenia Muscle ; 10(6): 1339-1346, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31436047

RESUMO

BACKGROUND: A poor fat-soluble micronutrient (FMN) and a high oxidative stress status are associated with frailty. Our aim was to determine the cross-sectional association of FMNs and oxidative stress biomarkers [protein carbonyls (PrCarb) and 3-nitrotyrosine] with the frailty status in participants older than 65 years. METHODS: Plasma levels of vitamins A (retinol), D3 , E (α-tocopherol and γ-tocopherol) and carotenoids (α-carotene and ß-carotene, lycopene, lutein/zeaxanthin, and ß-cryptoxanthin), PrCarb, and 3-nitrotyrosine were measured in 1450 individuals of the FRAILOMIC initiative. Participants were classified into robust, pre-frail, and frail using Fried's frailty criteria. Associations between biomarkers and frailty status were assessed by general linear and logistic regression models, both adjusted for cohort, season of blood sampling, gender, age, height, weight, and smoking. RESULTS: Robust participants had significantly higher vitamin D3 and lutein/zeaxanthin concentrations than pre-frail and frail subjects; had significantly higher γ-tocopherol, α-carotene, ß-carotene, lycopene, and ß-cryptoxanthin concentrations than frail subjects, and had significantly lower PrCarb concentrations than frail participants in multivariate linear models. Frail subjects were more likely to be in the lowest than in the highest tertile for vitamin D3 (adjusted odds ratio: 2.15; 95% confidence interval: 1.42-3.26), α-tocopherol (2.12; 1.39-3.24), α-carotene (1.69; 1.00-2.88), ß-carotene (1.84; 1.13-2.99), lycopene (1.94; 1.24-3.05), lutein/zeaxanthin (3.60; 2.34-5.53), and ß-cryptoxanthin (3.02; 1.95-4.69) and were more likely to be in the highest than in the lowest tertile for PrCarb (2.86; 1.82-4.49) than robust subjects in multivariate regression models. CONCLUSIONS: Our study indicates that both low FMN and high PrCarb concentrations are associated with pre-frailty and frailty.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31304964

RESUMO

High-sensitivity C-reactive protein (hsCRP) and homocysteine (Hcy) are inflammation markers but are also related to cardiovascular diseases, disability or higher risk of death. Although inflammation is considered to be associated with frailty, data regarding the association between hsCRP or Hcy and frailty are controversial or scarce, especially with respect to their association with pre-frailty. Thus, our objective was to study the association of hsCRP and Hcy with pre-frailty and frailty in 1211 Spanish men and women aged 65-98 years from the Toledo Study for Healthy Aging (TSHA) cohort, classified according to Fried's criteria. Hcy was independently associated with frailty (OR=1.06; 95% CI, 1.01 - 1.12), while hsCRP was independently associated with both pre-frailty (OR=1.03; 95% CI, 1.01 - 1.06) and frailty (OR=1.07; 95% CI, 1.02 - 1.12). Furthermore, both markers were positively correlated with the number of Fried's criteria that were met and were independently associated with the criteria of exhaustion (Hcy: OR=1.03, 95% CI, 1.00 - 1.06), weakness (hsCRP: OR=1.03, 95% CI, 1.01 - 1.05) and low physical activity (hsCRP: OR=1.04, 95% CI, 1.02 - 1.06). Thus, our results highlight the importance of inflammation in age-related physical decline and, in particular, its association with fatigue, low strength and decreased physical activity.

6.
Age Ageing ; 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31211360

RESUMO

OBJECTIVE: to evaluate the relationship between serum levels of the soluble Receptor for Advanced Glycation End-products (sRAGE) and mortality in frail and non-frail older adults. METHODS: we studied 691 subjects (141 frail and 550 non-frail) with a median age of 75 years from two population-based cohorts, the Toledo Study of Healthy Aging and the AMI study, who were enrolled to the FRAILOMIC initiative. Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between baseline sRAGE and mortality. RESULTS: during 6 years of follow-up 101 participants died (50 frail and 51 non-frail). Frail individuals who died had significantly higher sRAGE levels than those who survived (median [IQR]: 1563 [1015-2248] vs 1184 [870-1657] pg/ml, P = 0.006), whilst no differences were observed in the non-frail group (1262 [1056-1554] vs 1186 [919-1551] pg/ml, P = 0.19). Among frail individuals higher sRAGE levels were associated with an increased risk of death after adjustment for relevant covariates (HR = 2.72 per unit increment in ln-sRAGE, 95%CI 1.48-4.99, P = 0.001). In contrast, in non-frail individuals sRAGE showed no association with mortality. Survival curves demonstrated that among frail individuals the incidence of death was significantly higher in the top sRAGE quartile compared to the three lower quartiles (P = 0.002). Area under the ROC curve analysis demonstrated that for frail individuals, inclusion of sRAGE in the hazard model increased its predictive accuracy by ~3%. CONCLUSIONS: sRAGE is an independent predictor of mortality among frail individuals. Determination of sRAGE in frail subjects could be useful for prognostic assessment and treatment stratification.

7.
Scand J Med Sci Sports ; 29(10): 1591-1603, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31169924

RESUMO

Oxidative stress is associated with disease severity and limb muscle dysfunction in COPD. Our main goal was to assess the effects of exercise training on systemic oxidative stress and limb muscle dysfunction in older people with COPD. Twenty-nine outpatients with COPD (66-90 years) were randomly assigned to a 12-week exercise training (ET; high-intensity interval training (HIIT) plus power training) or a control (CT; usual care) group. We evaluated mid-thigh muscle cross-sectional area (CSA; computed tomography); vastus lateralis (VL) muscle thickness, pennation angle, and fascicle length (ultrasonography); peak VO2 uptake (VO2peak ) and work rate (Wpeak ) (incremental cardiopulmonary exercise test); rate of force development (RFD); maximal muscle power (Pmax ; force-velocity testing); systemic oxidative stress (plasma protein carbonylation); and physical performance and quality of life. ET subjects experienced changes in mid-thigh muscle CSA (+4%), VL muscle thickness (+11%) and pennation angle (+19%), VO2peak (+14%), Wpeak (+37%), RFD (+32% to 65%), Pmax (+38% to 51%), sit-to-stand time (-24%), and self-reported health status (+20%) (all P < 0.05). No changes were noted in the CT group (P > 0.05). Protein carbonylation decreased among ET subjects (-27%; P < 0.05), but not in the CT group (P > 0.05). Changes in protein carbonylation were associated with changes in muscle size and pennation angle (r = -0.44 to -0.57), exercise capacity (r = -0.46), muscle strength (r = -0.45), and sit-to-stand performance (r = 0.60) (all P < 0.05). The combination of HIIT and power training improved systemic oxidative stress and limb muscle dysfunction in older people with COPD. Changes in oxidative stress were associated with exercise-induced structural and functional adaptations.

8.
Exp Gerontol ; 124: 110637, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31199979

RESUMO

Frailty is a geriatric syndrome that leads not only to the loss of physical functions, but also to a generalized decline of the organism and a high risk of disability and dependency. Frailty's detection and management represent important goals for current gerontology. The advance in its rapid diagnosis could play a relevant role in taking measures to reduce the negative consequences it exerts on the body and to take preventive measures. microRNAs are the one of multiple epigenetic biomarkers that reflect functional changes in aged subject. In this review we analyze microRNAs as molecules involved in the control of the pathways leading to the development of frailty. miRNAs can be present in different body fluids, including plasma/serum and saliva, can be associated with organelles like the mitochondria, and can be expressed in tissues. Based on the multifactorial physiopathology of frailty, we analyzed here the microRNAs linked to "inflammaging" (inflamma-miRs), to musculoskeletal health (myomiRs), and microRNAs that can directly or indirectly affect the mitochondria (mitomiRs). Subsequently, we analyze those microRNAs that can be modified by physical exercise. In this review we will analyze the latest experimental studies carried out in animals, cell cultures, and human samples, with the aim to identify gaps in the research and in order to try to dazzle the information about the pathways regulated by each miRNA. Multiple studies revised here suggest that several miRs can be considered as possible markers of frailty, including miR-1, miR-21, miR-34a, miR-146a, miR-185, and miR-206, miR-223, among others. Normalization of miRNAs data and standardization of the protocols used for their measurement to avoid confounding variables influencing the results, are important to use miRNAs as disease biomarkers.

9.
Nat Chem ; 11(7): 638-643, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31133740

RESUMO

All real processes, be they chemical, mechanical or electrical, are thermodynamically irreversible and therefore suffer from thermodynamic losses. Here, we report the design and operation of a chemical reactor capable of approaching thermodynamically reversible operation. The reactor was employed for hydrogen production via the water-gas shift reaction, an important route to 'green' hydrogen. The reactor avoids mixing reactant gases by transferring oxygen from the (oxidizing) water stream to the (reducing) carbon monoxide stream via a solid-state oxygen reservoir consisting of a perovskite phase (La0.6Sr0.4FeO3-δ). This reservoir is able to remain close to equilibrium with the reacting gas streams because of its variable degree of non-stoichiometry and thus develops a 'chemical memory' that we employ to approach reversibility. We demonstrate this memory using operando, spatially resolved, real-time, high-resolution X-ray powder diffraction on a working reactor. The design leads to a reactor unconstrained by overall chemical equilibrium limitations, which can produce essentially pure hydrogen and carbon dioxide as separate product streams.

10.
J Am Med Dir Assoc ; 20(11): 1451-1457, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31078485

RESUMO

OBJECTIVES: Frailty is a geriatric syndrome that identifies individuals at higher risk of disability, institutionalization, and death. We previously reported that frailty is related to oxidative stress and cognitive impairment-related biomarkers. The aim of this study was to determine whether frailty is associated with genetic variants. DESIGN: Longitudinal population-based cohort of 2488 community-dwelling people from Toledo, Spain, aged 65 years or older. SETTING AND PARTICIPANTS: We obtained blood samples from 78 individuals with frailty and 74 nonfrail individuals who were nonfrail (according to Fried criteria) from the Toledo Study of Healthy Ageing and extracted DNA using the Chemagic DNA blood kit. MEASURES: Sample genotyping was carried out by means of Axiom Exome 319 Genotyping Array (Thermo Fisher Scientific), which contains 295,988 markers [single-nucleotide polymorphisms (SNPs) and rare variants], and transferred to the GeneTitan Instrument (Affymetrix). RESULTS: We found 15 SNPs (P < .001), 18 genes (P < .005), and 4 pathways (P < .05) related to cytokine-cytokine receptor interaction, natural killer cell-mediated cytotoxicity, regulation of autophagy, and renin-angiotensin system as the most strongly associated with frailty. CONCLUSIONS/IMPLICATIONS: The specific genetic features related to energy metabolism, biological processes regulation, cognition, and inflammation highlighted by this preliminary analysis offer useful insights for finding biologically meaningful biomarkers of frailty that allow early diagnosis and treatment. Further research is needed to confirm our novel findings in a larger population. Indeed, the EU-funded FRAILOMICS research effort will address this question.

11.
Histopathology ; 75(4): 496-507, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31025430

RESUMO

AIMS: To discern the differences in expression profiling of two histological subtypes of colorectal carcinoma (CRC) arising from the serrated route (serrated adenocarcinoma (SAC) and CRC showing histological and molecular features of a high level of microsatellite instability (hmMSI-H) both sharing common features (female gender, right-sided location, mucinous histology, and altered CpG methylation), but dramatically differing in terms of prognosis, development of an immune response, and treatment options. METHODS AND RESULTS: Molecular signatures of SAC and hmMSI-H were obtained by the use of transcriptomic arrays; quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were used to validate differentially expressed genes. An over-representation of innate immunity functions (granulomonocytic recruitment, chemokine production, Toll-like receptor signalling, and antigen processing and presentation) was obtained from this comparison, and intercellular cell adhesion molecule-1 (ICAM1) was more highly expressed in hmMSI-H, whereas two genes [those encoding calcitonin gene-related peptide-receptor component protein and C-X-C motif chemokine ligand 14 (CXCL14)] were more highly expressed in SAC. These array results were subsequently validated by qPCR, and by IHC for CXCL14 and ICAM1. Information retrieved from public databanks confirmed our findings. CONCLUSIONS: Our findings highlight specific functions and genes that provide a better understanding of the role of the immune response in the serrated pathological route and may be of help in identifying actionable molecules.

12.
Front Physiol ; 10: 316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30971950

RESUMO

This study aimed to evaluate the effect of the stretch-shortening cycle (SSC) on different portions of the force-velocity (F-V) relationship in older adults with and without chronic obstructive pulmonary disease (COPD), and to assess its association with physical function. The participants were 26 older adults with COPD (79 ± 7 years old; FEV1 = 53 ± 36% of predicted) and 10 physically active non-COPD (77 ± 4 years old) older adults. The F-V relationship was evaluated in the leg press exercise during a purely concentric muscle action and compared with that following an eccentric muscle action at 10% intervals of maximal unloaded shortening velocity (V0). Vastus lateralis (VL) muscle thickness, pennation angle (PA), and fascicle length (FL) were assessed by ultrasound. Habitual gait speed was measured over a 4-m distance. COPD subjects exhibited lower physical function and concentric maximal muscle power (Pmax) values compared with the non-COPD group (both p < 0.05). The SSC increased force and power values among COPD participants at 0-100 and 1-100% of V0, respectively, while the same was observed among non-COPD participants only at 40-90 and 30-90% of V0, respectively (all p < 0.05). The SSC induced greater improvements in force, but not power, among COPD compared with non-COPD subjects between 50 and 70% of V0 (all p < 0.05). Thus, between-group differences in muscle power were not statistically significant after the inclusion of the SSC (p > 0.05). The SSC-induced potentiation at 50-100% of V0 was negatively associated with physical function (r = -0.40-0.50), while that observed at 80-100% of V0 was negatively associated with VL muscle thickness and PA (r = -0.43-0.52) (all p < 0.05). In conclusion, older adults with COPD showed a higher SSC-induced potentiation compared with non-COPD subjects, which eliminated between-group differences in muscle power when performing SSC muscle actions. The SSC-induced potentiation was associated with lower physical function, VL muscle thickness, and VL PA values. The SSC-induced potentiation may help as a compensatory mechanism in those older subjects with a decreased ability to produce force/power during purely concentric muscle actions.

13.
Nutrients ; 11(3)2019 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-30857291

RESUMO

The aim of this study was to determine the relationship between bone mass (BM) and physical activity (PA) and sedentary behavior (SB) according to frailty status and sex using compositional data analysis. We analyzed 871 older people with an adequate nutritional status. Fried criteria were used to classify by frailty status. Time spent in SB, light intensity PA (LPA) and moderate-to-vigorous intensity PA (MVPA) was assessed from accelerometry for 7 days. BM was determined by dual-energy X-ray absorptiometry (DXA). The combined effect of PA and SB was significantly associated with BM in robust men and women (p ≤ 0.05). In relation to the other behaviors, SB was negatively associated with BM in robust men while BM was positively associated with SB and negatively with LPA and MVPA in robust women. Moreover, LPA also was positively associated with arm BM (p ≤ 0.01). Finally, in pre-frail women, BM was positively associated with MVPA. In our sample, to decrease SB could be a good strategy to improve BM in robust men. In contrast, in pre-frail women, MVPA may be an important factor to consider regarding bone health.


Assuntos
Composição Corporal/fisiologia , Densidade Óssea , Exercício/fisiologia , Fragilidade , Estado Nutricional , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino
14.
J Cachexia Sarcopenia Muscle ; 10(1): 188-198, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30920779

RESUMO

BACKGROUND: The associations between free-living physical activity (PA) and sedentary behaviour (SB) and sarcopenia in older people and its determinants are controversial. Self-reporting, the use of one-size-fits-all cut-points for intensity categorization when using accelerometers and the absence of a clear sarcopenia definition hampered explorations. The aim of this study is to describe the associations between objectively measured PA patterns and sarcopenia and its determinants. METHODS: Subjects aged >65 with valid accelerometry and sarcopenia-related measures from Toledo Study of Healthy Aging (TSHA) were included. Muscle mass (MM) was estimated by dual-energy X-ray absorptiometry. Handgrip strength (HS) was measured by dynamometry. Physical performance assessment relied on gait speed (GS). Sarcopenia presence was ascertained using Foundation for the National Institutes of Health (FNIH) criteria. PA and SB were estimated by ActiTrainer worn for 1 week and classified into time spent in SB and different PA intensity bands [light PA (LPA) and moderate-to-vigorous PA (MVPA)] using age-specific cut-points. Different multivariate linear and logistic regression models [(i) single-parameter, (ii) partition, and (iii) isotemporal substitution models] were used for estimating associations between PA, SB, and sarcopenia determinants and sarcopenia rates, respectively. All models adjusted for age, sex, co-morbidities (Charlson index), and functional ability (Katz and Lawton indexes). RESULTS: Five hundred twelve subjects from the TSHA had available data (78.08 ± 5.71 years of age; 54.3% women). FNIH sarcopenia assessment was performed in 497 subjects (23.3% were sarcopenic). In the linear regression, the single-parameter model showed an association between MVPA and all sarcopenia determinants. In the partition model, MVPA was associated with greater MM and GS. The isotemporal substitution showed that reallocating 1 h/day of MVPA displacing SB was associated with greater values in MM [ß = 0.014; 95% confidence interval (CI) = 0.004, 0.024; P < 0.01], GS (ß = 0.082; 95% CI = 0.054, 0.110; P < 0.001), and HS (ß = 0.888; 95% CI = 0.145, 1.631; P < 0.05). In the logistic regression, the single-parameter model yielded a significant association between 1 h/day increase in MVPA and sarcopenia reduction [odds ratio (OR) = 0.522; 95% CI = 0.367, 0.726; P < 0.001], as did the partition model (OR = 0.555; 95% CI = 0.376, 0.799; P < 0.01). The reallocation of 1 h/day SB only yielded a significant lower sarcopenia risk by almost 50% when it was substituted with MVPA, whereas the substitution of 15 min/day yielded a significant lower sarcopenia risk by 15% (P < 0.001) but did not show any association when it was substituted with LPA. CONCLUSIONS: An increase in MVPA replacing SB and LPA was associated with a reduction in sarcopenia prevalence and better performance across its determinants (MM, GS, and HS). LPA did not show any significant effect.

15.
Med Sci Sports Exerc ; 51(8): 1736-1744, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30829961

RESUMO

INTRODUCTION AND PURPOSE: Physical activity (PA) is considered the best nonpharmacological treatment for the decrease in bone mass (BM) produced during aging. Therefore, it is essential to assess how the time spent in PA is distributed to control further changes. This work examines the relationship between movement behaviors and BM during aging, using compositional data analysis. METHODS: We studied 227 older people 65 to 94 yr old (102 men and 125 women), divided by sex and bone status, over a period of 4 yr. Time spent in sedentary behavior (SB), light PA (LPA), and moderate to vigorous PA (MVPA), was assessed using accelerometry. BM was determined by dual-energy x-ray absorptiometry. RESULTS: The changes in MVPA were positively associated with the rate of BM decay at spine and leg in the whole sample and men's subgroup (P ≤ 0.05). In women, the rate of BM decay at spine and Ward's triangle were negatively associated with SB changes, and BM decay at femoral neck and Ward's triangle were positively associated with LPA (P ≤ 0.05). CONCLUSION: Increasing MVPA related to other movement behaviors produces improvements in the rate of bone change in older men, whereas to increase LPA and maintain MVPA would be the best approach to enhance BM in older women.

16.
Biosci Rep ; 39(3)2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30792263

RESUMO

A new familial dilated cardiomyopathy (FDCM) was found related to mutations in BAG3 gene. MicroRNAs (miRNAs) represent new targets of FDCM, although no studies have assessed clinical association between Bcl2-associated athanogene 3 (BAG3)-related DCM and miRNAs. Here, we studied whether a clinical association between BAG3-related FDCM and circulating miRNAs may have diagnostic and prognostic value in a small cohort of familial related individuals carrying a BAG3 mutation (BAG3+) and/or diagnosed of dilated cardiomyopathy (DCM) (DCM+). The analysis of 1759 circulating miRNAs showed significant differences between BAG3+ and BAG3- individuals for miRNAs mir-3191-3p, 6769b-3p, 1249-ep, 154-5p, 6855-5p, and 182-5p, while comparisons between BAG3+/DCM+ versus BAG3+/DCM- were restricted to miRNAs mir-154-5p, 6885-5p, and 182-5p, showing significant correlation with systolic and diastolic blood pressure, A wave, left atrium length, and left atrium area. Additionally, when stratified by gender and age, miRNAs were statistically correlated with critical parameters, including left ventricle ejection fraction (LVEF) and ventricular diameter, in women and young men. Likewise, 56% of BAG3+/DCM+, significantly co-expressed mir-154-5p and mir-182-5p, and a slight 4% did not express such combination, suggesting that co-expression of mir-154-5p and mir-182-5p may potentially show diagnostic value. Further studies will require long-term follow-up, and validation in larger populations.

17.
BMC Med Inform Decis Mak ; 19(1): 33, 2019 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30777059

RESUMO

BACKGROUND: Increasing life expectancy results in more elderly people struggling with age related diseases and functional conditions. This poses huge challenges towards establishing new approaches for maintaining health at a higher age. An important aspect for age related deterioration of the general patient condition is frailty. The frailty syndrome is associated with a high risk for falls, hospitalization, disability, and finally increased mortality. Using predictive data mining enables the discovery of potential risk factors and can be used as clinical decision support system, which provides the medical doctor with information on the probable clinical patient outcome. This enables the professional to react promptly and to avert likely adverse events in advance. METHODS: Medical data of 474 study participants containing 284 health related parameters, including questionnaire answers, blood parameters and vital parameters from the Toledo Study for Healthy Aging (TSHA) was used. Binary classification models were built in order to distinguish between frail and non-frail study subjects. RESULTS: Using the available TSHA data and the discovered potential predictors, it was possible to design, develop and evaluate a variety of different predictive models for the frailty syndrome. The best performing model was the support vector machine (SVM, 78.31%). Moreover, a methodology was developed, making it possible to explore and to use incomplete medical data and further identify potential predictors and enable interpretability. CONCLUSIONS: This work demonstrates that it is feasible to use incomplete, imbalanced medical data for the development of a predictive model for the frailty syndrome. Moreover, potential predictive factors have been discovered, which were clinically approved by the clinicians. Future work will improve prediction accuracy, especially with regard to separating the group of frail patients into frail and pre-frail ones and analyze the differences among them.


Assuntos
Envelhecimento , Mineração de Dados , Idoso Fragilizado , Fragilidade/diagnóstico , Aprendizado de Máquina , Aplicações da Informática Médica , Modelos Teóricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/epidemiologia , Inquéritos Epidemiológicos , Humanos , Masculino , Prognóstico , Fatores de Risco
18.
J Am Med Dir Assoc ; 20(5): 634-638.e1, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30738823

RESUMO

OBJECTIVES: To determine whether or not and to what extent the association between sedentary time and frailty was moderated by moderate-to-vigorous physical activity in older adults. DESIGN: Cross-sectional. SETTING: Community-dwelling individuals. PARTICIPANTS: 749 (403 females and 346 males) white older adults. MEASUREMENTS: Sedentary time and moderate-to-vigorous physical activity were measured with accelerometers. Frailty was objectively measured using the Frailty Trait Scale. All models were adjusted for age, sex, education, income, marital status, body mass index, moderate-to-vigorous physical activity, and accelerometer wear time. RESULTS: The regression model reported a significant effect of sedentary time on frailty (P < .05). Nevertheless, the results indicated that moderate-to-vigorous physical activity moderates the relationship between frailty status and sedentary time. The Johnson-Neyman technique determined that the estimated moderate-to-vigorous physical activity point was 27.25 minutes/d, from which sedentary time has no significant effect on frailty. CONCLUSIONS: Moderate-to-vigorous physical activity is a moderator in the relationship between sedentary time and frailty in older adults, offsetting the harmful effects of sedentary behavior with 27 minutes/d of moderate-to-vigorous activity. Engaging in moderate-to-vigorous physical activities should be encouraged. Reducing sedentary behavior may also be beneficial, particularly among inactive older adults.

19.
Hum Mol Genet ; 28(10): 1629-1644, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30624633

RESUMO

Mutations in MORC2 lead to an axonal form of Charcot-Marie-Tooth (CMT) neuropathy type 2Z. To date, 31 families have been described with mutations in MORC2, indicating that this gene is frequently involved in axonal CMT cases. While the genetic data clearly establish the causative role of MORC2 in CMT2Z, the impact of its mutations on neuronal biology and their phenotypic consequences in patients remains to be clarified. We show that the full-length form of MORC2 is highly expressed in both embryonic and adult human neural tissues and that Morc2 expression is dynamically regulated in both the developing and the maturing murine nervous system. To determine the effect of the most common MORC2 mutations, p.S87L and p.R252W, we used several in vitro cell culture paradigms. Both mutations induced transcriptional changes in patient-derived fibroblasts and when expressed in rodent sensory neurons. These changes were more pronounced and accompanied by abnormal axonal morphology, in neurons expressing the MORC2 p.S87L mutation, which is associated with a more severe clinical phenotype. These data provide insight into the neuronal specificity of the mutated MORC2-mediated phenotype and highlight the importance of neuronal cell models to study the pathophysiology of CMT2Z.

20.
Exp Gerontol ; 115: 114-121, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30528641

RESUMO

OBJECTIVES: The aim was to establish whether a short supervised facility-based exercise program improved frailty, physical function and performance in comparison with usual care treatment. METHODS: This was a quasi-experimental, non-randomized controlled intervention study in frail (2.75 ±â€¯1.25 Frailty Phenotype criteria) older adults (range:77.2-95.8 years). The exercise (EX) group (n = 11) performed concurrent training (power training + high-intensity interval training, HIIT) twice weekly for 6 weeks while the control (CT) group (n = 9) followed usual care. RESULTS: The exercise intervention improved frailty status in 64% of the subjects improving Frailty Phenotype by 1.6 points (95%CI 0.8-2.5, p < 0.05), and increasing SPPB score by 3.2 points (95%CI: 2.4-4.0, Cohen's d = 2.0, p < 0.05), muscle power by 47% (95%CI: 7-87%, Cohen's d = 0.5, p < 0.05), muscle strength by 34%(95%CI: 7-60, Cohen's d = 0.6, p < 0.05) and the aerobic capacity by 19% (6 minute walking test +45 m, 95%CI: 7-83, Cohen's d = 0.7, p = 0.054). The CT did not experience any significant changes in frailty status, physical function or performance. CONCLUSIONS: A short concurrent exercise program of muscle power and walking-based HIIT training is a feasible and safe method to increase physical performance and improve function and frailty in elder (pre)frail patients.


Assuntos
Terapia por Exercício/métodos , Fragilidade/prevenção & controle , Envelhecimento Saudável , Força Muscular , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Teste de Esforço , Tolerância ao Exercício , Feminino , Idoso Fragilizado , Fragilidade/fisiopatologia , Avaliação Geriátrica , Humanos , Masculino , Projetos Piloto , Método Simples-Cego , Espanha
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