RESUMEN
Non-smokers exposed to second-hand smoke (SHS) present risk of developing tobacco smoke-associated pathologies. To investigate the airway molecular response to SHS exposure that could be used in health risk assessment, comparative shotgun proteomics was performed on nasal epithelium from a group of healthy restaurant workers, non-smokers (never and former) exposed and not exposed to SHS in the workplace. HIF1α-glycolytic targets (GAPDH, TPI) and proteins related to xenobiotic metabolism, cell proliferation and differentiation leading to cancer (ADH1C, TUBB4B, EEF2) showed significant modulation in non-smokers exposed. In never smokers exposed, enrichment of glutathione metabolism pathway and EEF2-regulating protein synthesis in genotoxic response were increased, while in former smokers exposed, proteins (LYZ, ATP1A1, SERPINB3) associated with tissue damage/regeneration, apoptosis inhibition and inflammation that may lead to asthma, COPD or cancer, were upregulated. The identified proteins are potential response and susceptibility/risk biomarkers for SHS exposure.
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Mucosa Nasal , Exposición Profesional , Proteómica , Contaminación por Humo de Tabaco , Humanos , Contaminación por Humo de Tabaco/efectos adversos , Exposición Profesional/efectos adversos , Mucosa Nasal/metabolismo , Mucosa Nasal/efectos de los fármacos , Adulto , Masculino , Restaurantes , Femenino , Persona de Mediana EdadRESUMEN
Ubiquitin-dependent control of mitochondrial dynamics is important for protein quality and neuronal integrity. Mitofusins, mitochondrial fusion factors, can integrate cellular stress through their ubiquitylation, which is carried out by multiple E3 enzymes in response to many different stimuli. However, the molecular mechanisms that enable coordinated responses are largely unknown. Here we show that yeast Ufd2, a conserved ubiquitin chain-elongating E4 enzyme, is required for mitochondrial shape adjustments. Under various stresses, Ufd2 translocates to mitochondria and triggers mitofusin ubiquitylation. This elongates ubiquitin chains on mitofusin and promotes its proteasomal degradation, leading to mitochondrial fragmentation. Ufd2 and its human homologue UBE4B also target mitofusin mutants associated with Charcot-Marie-Tooth disease, a hereditary sensory and motor neuropathy characterized by progressive loss of the peripheral nerves. This underscores the pathophysiological importance of E4-mediated ubiquitylation in neurodegeneration. In summary, we identify E4-dependent mitochondrial stress adaptation by linking various metabolic processes to mitochondrial fusion and fission dynamics.
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Mitocondrias , Proteínas Mitocondriales , Ubiquitina-Proteína Ligasas , Humanos , Aclimatación , Mitocondrias/metabolismo , Saccharomyces cerevisiae/metabolismo , Ubiquitina , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Proteínas Mitocondriales/metabolismoRESUMEN
Defects in mitochondrial fusion are at the base of many diseases. Mitofusins power membrane-remodeling events via self-interaction and GTP hydrolysis. However, how exactly mitofusins mediate fusion of the outer membrane is still unclear. Structural studies enable tailored design of mitofusin variants, providing valuable tools to dissect this stepwise process. Here, we found that the two cysteines conserved between yeast and mammals are required for mitochondrial fusion, revealing two novel steps of the fusion cycle. C381 is dominantly required for the formation of the trans-tethering complex, before GTP hydrolysis. C805 allows stabilizing the Fzo1 protein and the trans-tethering complex, just prior to membrane fusion. Moreover, proteasomal inhibition rescued Fzo1 C805S levels and membrane fusion, suggesting a possible application for clinically approved drugs. Together, our study provides insights into how assembly or stability defects in mitofusins might cause mitofusin-associated diseases and uncovers potential therapeutic intervention by proteasomal inhibition.
RESUMEN
In this protocol, we describe the analysis of protein stability over time, using synthesis shutoff. As an example, we express HA-tagged yeast mitofusin Fzo1 in Saccharomyces cerevisiae and inhibit translation via cycloheximide (CHX). Proteasomal inhibition with MG132 is performed, as an optional step, before the addition of CHX. Proteins are extracted via trichloroacetic acid (TCA) precipitation and subsequently separated via SDS-PAGE. Immunoblotting and antibody-decoration are performed to detect Fzo1 using HA-specific antibodies. We have adapted the method of blocking protein translation with cycloheximide to analyze the stability of high molecular weight proteins, including post-translational modifications and their impact on protein turnover.
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Juglans/química , Lipoproteínas/efectos de los fármacos , Anciano , Femenino , Humanos , MasculinoRESUMEN
Environmental tobacco smoke (ETS) has been recognized as a major health hazard by environmental and public health authorities worldwide. In Portugal, smoke-free laws are in force for some years, banning smoking in most indoor public spaces. However, in hospitality venues such as restaurants and bars, owners can still choose between a total smoke-free policy or a partial smoking restriction with designated smoking areas, if adequate reinforced ventilation systems are implemented. Despite that, a previous study showed that workers remained continuously exposed to higher ETS pollution in Lisbon restaurants and bars where smoking was still allowed, comparatively to total smoke-free venues. This was assessed by measurements of indoor PM2.5 and urinary cotinine, a biomarkers of tobacco smoke exposure, demonstrating that partial smoking restrictions do not effectively protect workers from ETS. The aim of the present work was to characterize effect and susceptibility biomarkers in non-smokers from those hospitality venues occupationally exposed to ETS comparatively to non-exposed ones. A group of smokers was also included for comparison. The sister chromatid exchange (SCE), micronucleus (MN) and comet assays in whole peripheral blood lymphocytes (PBLs) and the micronucleus assay in exfoliated buccal cells, were used as biomarkers of genotoxicity. Furthermore, a comet assay after ex vivo challenge of leukocytes with an alkylating agent, ethyl methanesulfonate (EMS), was used to analyze the repair capacity of those cells. Genetic polymorphisms in genes associated with metabolism and DNA repair were also included. The results showed no clear association between occupational exposure to ETS and the induction of genotoxicity. Interestingly, the leukocytes from non-smoking ETS-exposed individuals displayed lower DNA damage levels in response to the ex vivo EMS challenge, in comparison to those from non-exposed workers, suggesting a possible adaptive response. The contribution of individual susceptibility to the effect biomarkers studied was unclear, deserving further investigation.
Asunto(s)
Contaminación por Humo de Tabaco , Biomarcadores , Humanos , Mucosa Bucal/química , Portugal/epidemiología , Restaurantes , Contaminación por Humo de Tabaco/efectos adversosRESUMEN
BACKGROUND AND PURPOSE: The red blood cell fatty acid composition objectively reflects the long-term dietary intake of several fatty acids. In patients undergoing carotid endarterectomy, we explored whether red blood cell status of selected fatty acids related to symptomatic carotid artery disease. METHODS: We included patients with symptomatic (n=22) and asymptomatic (n=23) carotid artery disease. We determined all-C18:1 trans, linoleic acid (LA, C18:2n6), alpha-linolenic acid (C18:3n3), and the omega-3 index (sum of eicosapentaenoic [C20:5n3] and docosahexaenoic [C22:6n3] acids) in both red blood cells and carotid plaque phospholipids by gas-chromatography. RESULTS: In a multivariate logistic regression analysis, we only observed a significant association for LA, whose red blood cell status was inversely related to symptomatic carotid artery disease (odds ratio, 0.116 [95% CI, 0.022-0.607], P=0.011, for each 1-SD increase). A similar result was observed for LA in carotid plaque phospholipids. CONCLUSIONS: Cell membrane enrichment in LA, which reflects its intake, was inversely related to symptomatic carotid disease. This increases evidence supporting a favorable role of dietary LA in vascular health.
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Enfermedades de las Arterias Carótidas/epidemiología , Enfermedades de las Arterias Carótidas/metabolismo , Membrana Eritrocítica/química , Ácido Linoleico/metabolismo , Anciano , Anciano de 80 o más Años , Cromatografía de Gases , Endarterectomía Carotidea , Membrana Eritrocítica/metabolismo , Eritrocitos/química , Ácidos Grasos/sangre , Ácidos Grasos Omega-3/sangre , Femenino , Humanos , Masculino , Fosfolípidos/sangre , Placa Aterosclerótica , PrevalenciaAsunto(s)
Dieta Saludable/tendencias , Mediadores de Inflamación/antagonistas & inhibidores , Mediadores de Inflamación/sangre , Juglans , Anciano , Biomarcadores/sangre , Dieta Saludable/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Nut consumption may reduce age-related diseases and lead to better health and well-being in aging. Many conditions of aging develop over decades, and thus earlier lifestyle factors may particularly influence later health. METHODS: In 1998 and 2002, we administered food frequency questionnaires to assess nut consumption (peanuts, walnuts, and other nuts and peanut butter) in women in the Nurses' Health Study in their 50 s/early 60 s. In 2012, those who survived beyond 65 years with no chronic diseases, no reported memory impairment, no physical disabilities, and intact mental health were considered "healthy agers." We used multivariable logistic regression to estimate odds ratios for healthy versus usual aging, controlled for sociodemographic, behavioral, dietary, and other potential confounding factors. RESULTS: Of 33,931 participants at midlife, 16% became "healthy agers." After age adjustment, we observed a significant association between total nut consumption at midlife and higher odds of healthy aging, with strongest associations observed excluding peanut butter (odds ratio (OR) = 1.46, 95% confidence interval (CI) 1.32-1.62, ≥3 servings/week versus none). Findings were attenuated after further control for covariates, including overall diet quality (OR = 1.14, 95% CI 1.02-1.28, P trend = 0.05). For nut types, we found statistically significantly higher odds of healthy aging across peanuts, walnuts, and other nuts after age adjustment. After full control for confounders, only walnut consumption remained associated with healthy aging (P trend = 0.0001); for example, the OR was 1.20 (95% CI 1.00-1.44) for ≥2 servings/week versus none. CONCLUSIONS: Women consuming nuts at midlife have a greater likelihood of overall health and well-being at older ages. Nut consumption may represent a simple intervention to explore and promote healthy aging.
RESUMEN
BACKGROUND: Walnut consumption counteracts oxidative stress and inflammation, 2 drivers of cognitive decline. Clinical data concerning effects on cognition are lacking. OBJECTIVES: The Walnuts And Healthy Aging study is a 2-center (Barcelona, Spain; Loma Linda, CA) randomized controlled trial examining the cognitive effects of a 2-y walnut intervention in cognitively healthy elders. METHODS: We randomly allocated 708 free-living elders (63-79 y, 68% women) to a diet enriched with walnuts at â¼15% energy (30-60 g/d) or a control diet (abstention from walnuts). We administered a comprehensive neurocognitive test battery at baseline and 2 y. Change in the global cognition composite was the primary outcome. We performed repeated structural and functional brain MRI in 108 Barcelona participants. RESULTS: A total of 636 participants completed the intervention. Besides differences in nutrient intake, participants from Barcelona smoked more, were less educated, and had lower baseline neuropsychological test scores than those from Loma Linda. Walnuts were well tolerated and compliance was good. Modified intention-to-treat analyses (n = 657) uncovered no between-group differences in the global cognitive composite, with mean changes of -0.072 (95% CI: -0.100, -0.043) in the walnut diet group and -0.086 (95% CI: -0.115, -0.057) in the control diet group (P = 0.491). Post hoc analyses revealed significant differences in the Barcelona cohort, with unadjusted changes of -0.037 (95% CI: -0.077, 0.002) in the walnut group and -0.097 (95% CI: -0.137, -0.057) in controls (P = 0.040). Results of brain fMRI in a subset of Barcelona participants indicated greater functional network recruitment in a working memory task in controls. CONCLUSIONS: Walnut supplementation for 2 y had no effect on cognition in healthy elders. However, brain fMRI and post hoc analyses by site suggest that walnuts might delay cognitive decline in subgroups at higher risk. These encouraging but inconclusive results warrant further investigation, particularly targeting disadvantaged populations, in whom greatest benefit could be expected.This trial was registered at clinicaltrials.gov as NCT01634841.
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Disfunción Cognitiva/dietoterapia , Juglans/metabolismo , Nueces/metabolismo , Anciano , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/psicología , Femenino , Envejecimiento Saludable , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria , Persona de Mediana Edad , EspañaRESUMEN
Mitochondria are essential organelles whose function is upheld by their dynamic nature. This plasticity is mediated by large dynamin-related GTPases, called mitofusins in the case of fusion between two mitochondrial outer membranes. Fusion requires ubiquitylation, attached to K398 in the yeast mitofusin Fzo1, occurring in atypical and conserved forms. Here, modelling located ubiquitylation to α4 of the GTPase domain, a critical helix in Ras-mediated events. Structure-driven analysis revealed a dual role of K398. First, it is required for GTP-dependent dynamic changes of α4. Indeed, mutations designed to restore the conformational switch, in the absence of K398, rescued wild-type-like ubiquitylation on Fzo1 and allowed fusion. Second, K398 is needed for Fzo1 recognition by the pro-fusion factors Cdc48 and Ubp2. Finally, the atypical ubiquitylation pattern is stringently required bilaterally on both involved mitochondria. In contrast, exchange of the conserved pattern with conventional ubiquitin chains was not sufficient for fusion. In sum, α4 lysines from both small and large GTPases could generally have an electrostatic function for membrane interaction, followed by posttranslational modifications, thus driving membrane fusion events.
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GTP Fosfohidrolasas/química , GTP Fosfohidrolasas/metabolismo , Fusión de Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimología , Ubiquitinación/genética , GTP Fosfohidrolasas/genética , Proteínas de la Membrana/genética , Mitocondrias/metabolismo , Dinámicas Mitocondriales/genética , Membranas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mutantes/metabolismo , Plásmidos/genética , Conformación Proteica en Hélice alfa , Dominios Proteicos , Procesamiento Proteico-Postraduccional/genética , Proteínas de Saccharomyces cerevisiae/genética , Ubiquitina/metabolismoRESUMEN
BACKGROUND: In children, nutritional status of vitamin D (vitD), frequency of vitD receptor (VDR) gene polymorphisms and their associations with overweight and asthma remain controversial. OBJECTIVES: To evaluate the nutritional status of vitD and the frequency of VDR gene polymorphisms, as well as identify their associations with nutritional status and asthma. METHODS: A cross-sectional study was conducted with schoolchildren (n = 262; mean age = 8.7 ± 1.3 years). Clinical history, anthropometric measurements, and serum 25-hydroxy vitD were evaluated. Four VDR gene polymorphisms were identified and genotypes, alleles, and haplotypes were calculated. RESULTS: The serum vitD levels were found at 85.1%, within normal range. The FokI AA genotype was more frequent in asthmatics compared to healthy controls (10 vs. 1%, p < 0.05), while the GG genotype was less frequent (45.0 vs. 55.2%, p < 0.05). The frequency of the TT allele for the ApaI was higher among asthmatic eutrophic children (60.9 vs. 29.4%, p < 0.05) and that of the TT allele for the BsmI was higher among asthmatic overweight children (35.3 vs. 4.4%, p < 0.05). CONCLUSIONS: Insufficiency in vitD was low. Two wild-type alleles (AA) of FokI were identified as risk factor for the development of asthma, while GG alleles appears to be a protective factor. To have polymorphic alleles (TT) of ApaI seems to be a risk factor for asthma in children with normal weight, while that of BsmI seems to be a risk factor for asthma in overweight condition. Serum vitD was not different among analyzed genotypes.
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Asma/genética , Predisposición Genética a la Enfermedad , Sobrepeso/genética , Receptores de Calcitriol/genética , Asma/sangre , Brasil , Estudios de Casos y Controles , Niño , Estudios Transversales , Femenino , Frecuencia de los Genes , Humanos , Masculino , Sobrepeso/sangre , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Vitamina D/sangreRESUMEN
Mitofusins are dynamin-related GTPases that drive mitochondrial fusion by sequential events of oligomerization and GTP hydrolysis, followed by their ubiquitylation. Here, we show that fusion requires a trilateral salt bridge at a hinge point of the yeast mitofusin Fzo1, alternatingly forming before and after GTP hydrolysis. Mutations causative of Charcot-Marie-Tooth disease massively map to this hinge point site, underlining the disease relevance of the trilateral salt bridge. A triple charge swap rescues the activity of Fzo1, emphasizing the close coordination of the hinge residues with GTP hydrolysis. Subsequently, ubiquitylation of Fzo1 allows the AAA-ATPase ubiquitin-chaperone Cdc48 to resolve Fzo1 clusters, releasing the dynamin for the next fusion round. Furthermore, cross-complementation within the oligomer unexpectedly revealed ubiquitylated but fusion-incompetent Fzo1 intermediates. However, Cdc48 did not affect the ubiquitylated but fusion-incompetent variants, indicating that Fzo1 ubiquitylation is only controlled after membrane merging. Together, we present an integrated model on how mitochondrial outer membranes fuse, a critical process for their respiratory function but also putatively relevant for therapeutic interventions.
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GTP Fosfohidrolasas/química , GTP Fosfohidrolasas/metabolismo , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Dinámicas Mitocondriales/fisiología , Proteínas Mitocondriales/química , Proteínas Mitocondriales/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteína que Contiene Valosina/química , Proteína que Contiene Valosina/metabolismo , Animales , Fibroblastos , Fusión de Membrana/fisiología , Ratones , Mitocondrias/metabolismo , Membranas Mitocondriales/química , Modelos Moleculares , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Saccharomyces cerevisiae , Ubiquitina/química , Ubiquitina/metabolismo , UbiquitinaciónRESUMEN
The objective of this study was to investigate the reproducibility of the International System for the Detection and Evaluation of Caries (ICDAS) for the diagnosis of caries by students of the Master's Degree in Dentistry (n = 25). The occlusal surfaces of human third molars (n = 14) were evaluated by twenty-five (n = 25) students using the ICDAS index and later a questionnaire was applied on demographic and professional context data. The dental crowns were sectioned in mesial to distal direction to obtain slices of 1mm in thickness which were observed in a stereomicroscope (40X) to identify the greatest extension of caries lesion. Data were analyzed by the Chi-Square, Fisher's Exact and Spearman's Correlation Coefficient at a significance level of 5%. There was an influence in the diagnosis of caries among students and teeth, where the majority of those who declared themselves to be safe missed the diagnosis. There was variability between the diagnosis and the proposed treatment for caries, with a better diagnosis for tooth VII and less for X; greater fit for treatment of teeth XIII, XIV and lower for IV, VI. The histological cut showed that the teeth were more affected by caries than the ICDAS. It was concluded that the ICDAS reproducibility was partially satisfactory when the occlusal surface was evaluated by the master's degree students. (AU).
Este trabalho teve o objetivo de investigar a reprodutibilidade do Sistema Internacional de Detecção e Avaliação de Cárie (ICDAS) para o diagnóstico da cárie, por estudantes de curso de Mestrado em Odontologia (n=25). As superfícies oclusais de terceiros molares humanos (n=14) foram avaliadas por vinte e cinco (n=25) estudantes, utilizando o índice ICDAS, e posteriormente foi aplicado questionário sobre dados demográficos e de contexto profissional. As coroas dentárias foram seccionadas no sentido mésio distal para obter fatias de 1 mm de espessura, que foram observadas em estereomicroscópio (40X) para identificar a maior extensão da lesão de cárie. Os dados foram analisados pelos Testes Qui-Quadrado, Exato de Fisher e Coeficiente de Correlação de Spearman, em nível de significância de 5%. Houve influência do grau de instrução dos estudantes no diagnóstico da cárie em relação ao dente avaliado e a maioria que se declarou segura errou o diagnóstico. Houve variabilidade entre o diagnóstico e o tratamento proposto para a cárie, com maior acerto para diagnóstico do dente VII e menor para o X; maior acerto para tratamento dos dentes XIII, XIV e menor para IV, VI. O corte histológico mostrou que os dentes estavam mais comprometidos pela cárie que o ICDAS. Concluiu-se que a reprodutibilidade do ICDAS foi satisfatória quando a superfície oclusal foi avaliada pelos mestrandos. (AU).
RESUMEN
The digital radiograph represents a great advance in oral maxillofacial radiology because it incorporates informatics technology in the capture, interpretation, and archiving of radiographic images. Previous studies have demonstrated that it is possible to use gray values in bone lesion diagnosis and follow-up. However, these applications depend on radiograph system quality and exposure time. The aim of this study was to evaluate the gray-value reproducibility and noise produced by Dabi Atlante's IDA system, a direct digital radiography system. Radiographs were obtained in a standardized manner (70 kV, 7 mA, and 2.2-mm filtration) with a direct digital sensor and a stepwedge placed in a phantom at a 30-cm focus-film distance. Ten consecutive x-ray imaging series were completed at 0.10-s, 0.15-s, and 0.20-s exposure times. Gray values were analyzed in five regions of interest (ROIs): bone tissue (BT), soft tissue (ST), and three stepwedge steps (Step 1, Step 2, and Step 3). Mean gray values differed significantly across exposure times (p < .05) in all five ROIs. The ROI with the greatest gray-value variability (25.36%) and noise (9.46%) was ST. In conclusion, gray-value reproducibility and noise of the IDA system vary across areas with differing radiolucency. Thus, special attention is necessary for the diagnosis and follow-up of radiolucent lesions due to relatively high gray-value interference (AU).
A radiografia digital representa um grande avanço na radiologia bucomaxilofacial porque incorpora a tecnologia informática na captura, interpretação e arquivamento de imagens radiográficas. Estudos anteriores demonstraram que é possível usar os valores de cinza no diagnóstico e na proservação das lesões ósseas. No entanto, essas aplicações dependem da qualidade do sistema radiológico e do tempo de exposição. O objetivo deste estudo foi avaliar a reprodutibilidade do valor de cinza e o ruído produzido pelo sistema IDA da Dabi Atlante, um sistema de radiografia digital direto. As radiografias foram obtidas de maneira padronizada (70 kV, 7 mA e filtração de 2,2 mm) com um sensor digital direto e um penetrômetro colocados em um fantoma a uma distância de filme-foco de 30 cm. Dez imagens radiográficas consecutivas foram obtidas com tempos de exposição de 0,10-s, 0,15-s e 0,20-s. Os valores de cinza foram analisados em cinco regiões de interesse (ROIs): tecido ósseo (TO), tecido mole (TM) e três degraus do penetrômetro (Degrau 1, Degrau 2 e Degrau 3). Os valores de cinza médios diferiram significativamente entre os tempos de exposição (p <0,05) em todos as cinco ROIs. A ROI com maior variabilidade do valor de cinza (25,36%) e ruído (9,46%) foi TM. Em conclusão, a reprodutibilidade do valor de cinza e o ruído do sistema IDA variam entre áreas com radiolucência diferente. Assim, atenção especial é necessária para o diagnóstico e proservação de lesões radiolucentes devido à interferência dos valores cinza relativamente alta. (AU).
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Nut consumption lowers blood cholesterol and is associated with reduced cardiovascular disease, but effects on blood pressure (BP) are inconsistent. We assessed the 2-year effects of a walnut diet versus a control diet on office BP and 24-hours ambulatory BP in free-living elders participating in the Walnuts and Healthy Aging study, a randomized trial testing the effects of walnuts at ≈15% energy on age-related disorders. In a prespecified analysis, we enrolled 305 participants, of whom 236 (75%) completed the study (65% women; age, 69 years; 60% with mild hypertension). Walnuts were well tolerated, and compliance was >98%. Mean baseline office BP was 128/79 mm Hg. Adjusted changes from baseline in mean office systolic BP were -4.61 mm Hg (95% CI, -7.43 to -1.79 mm Hg) in the walnut group and -0.59 mm Hg (-3.38 to 2.21 mm Hg) in controls ( P=0.051). Respective changes in mean systolic 24-hour ambulatory BP were -3.86 mm Hg (CI, -5.45 to -2.26 mm Hg) and -2.00 mm Hg (CI, -3.58 to -0.42 mm Hg; P=0.111). No changes in diastolic BP were observed. In participants in the upper tertile of baseline 24-hour ambulatory systolic BP (>125 mm Hg), mean 2-year systolic 24-hour BP was -8.5 mm Hg (CI, -12 to -5.0 mm Hg) in the walnut group and -2.5 mm Hg (CI, -6.3 to 1.3 mm Hg) in controls ( P=0.034). During the trial, participants in the walnut group required less uptitration of antihypertensive medication and had better overall BP regulation than controls. Walnut consumption reduces systolic BP in elderly subjects, particularly in those with mild hypertension. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT01634841 .
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Envejecimiento/fisiología , Monitoreo Ambulatorio de la Presión Arterial/métodos , Presión Sanguínea/fisiología , Dieta/métodos , Hipertensión/prevención & control , Juglans , Anciano , Femenino , Estudios de Seguimiento , Voluntarios Sanos , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND & AIMS: Shortening of leukocyte telomere length (LTL) is a biomarker of aging. Epidemiologic studies of LTL in relation to dietary fatty acids have reported conflicting results. The red blood cell (RBC) fatty acid status is a valid objective biomarker of long-term dietary intake of C18:2n-6, C18:3n-3 and long-chain n-3 polyunsaturated fatty acids (C20:5n-3 and C22:6n-3). In healthy older individuals, we investigated whether LTL relates to the RBC proportions of the main dietary polyunsaturated fatty acids (PUFA), and to the RBC proportion of arachidonic acid (C20:4n-6), a fatty acid that can generate pro-inflammatory lipid mediators once released from cell membranes. DESIGN: Cross-sectional study in 344 subjects (mean age 68.8 y, 68.6% women) who participated in a randomized controlled trial testing whether a diet enriched in walnuts can delay the onset of age-related diseases (https://clinicaltrials.gov/ct2/show/NCT01634841). At baseline, we assessed LTL by high-throughput quantitative fluorescence and determined fatty acids in RBCs by gas chromatography. RESULTS: In multivariate models adjusted for age and gender, the RBC proportions of dietary PUFA were unrelated to LTL. In contrast, the RBC proportion of arachidonic acid inversely related to LTL (regression coefficient [95% confidence interval], -0.10 (-0.19 to -0.01), P = 0.023). CONCLUSION: An increasing proportion of C20:4n-6 in RBCs is associated with shorter telomeres. Further research is needed to investigate the role of this fatty acid and its derived lipid mediators in the aging process.
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Envejecimiento/fisiología , Ácido Araquidónico/sangre , Eritrocitos/química , Leucocitos/química , Telómero/química , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , España/epidemiologíaRESUMEN
Randomized controlled trials on diet and shortening of leukocyte telomere length (LTL) mostly focus on marine-derived n-3 polyunsaturated fatty acids (PUFA). Walnuts are a sustainable source of n-3 PUFA. We investigated whether inclusion of walnuts (15% of energy) in the diet for 2 years would maintain LTL in cognitively healthy elders (63â»79 years old) compared to a control group (habitual diet, abstaining from walnuts). This opportunistic sub-study was conducted within the Walnuts and Healthy Aging study, a dual-centre (Barcelona, Spain and Loma Linda University, California) parallel trial. A sub-set of the Barcelona site participants were randomly assigned to the walnut (n = 80) or control group (n = 69). We assessed LTL at baseline and at 2 years and we conducted repeated-measures ANCOVA with 2 factors: time (baseline, 2 years) and group (control, walnut) and their interaction. Adjusted means (95% confidence interval) of LTL (in kb) in controls were 7.360 (7.084,7.636) at baseline and 7.061 (6.835,7.288) after 2 years; corresponding values in the walnut group were 7.064 (6.807,7.320) and 7.074 (6.864,7.284). The time × intervention interaction was nearly significant (p = 0.079), suggestive of a trend of walnut consumption in preserving LTL. This exploratory research finding should be confirmed in trials with adequate statistical power.
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Dieta , Juglans , Leucocitos/química , Telómero/genética , Anciano , Envejecimiento/fisiología , Biomarcadores/sangre , California , Femenino , Humanos , Masculino , Persona de Mediana Edad , España , Ácido alfa-Linolénico/sangreRESUMEN
PURPOSE OF REVIEW: There is increasing interest in exploring whether age-related diseases can be prevented by dietary means through nutrients or food bioactives, whole foods, or specific dietary patterns. Because of the slow nature of the aging process, biomarkers such as telomere length are helpful for this purpose. Here we update the developments in the area during the last 2 years. RECENT FINDINGS: Most data stem from epidemiologic studies, often cross-sectional in design. Recent articles strengthened the link between consumption of sugar-sweetened beverages and telomere shortening, whereas a novel association between telomere length and drinking coffee has been uncovered. Controversy on meat consumption and telomere length persists, mostly because of the presumed different effects of total meat and processed meat. In general terms, increasing consumption of antioxidant-rich plant foods relates to maintained telomere length. Feeding intervention trials with outcomes on telomere length are few and thus far have contributed little to further knowledge on this topic. SUMMARY: Epidemiologic studies provide support for the putative effects of diet components on telomere length and on the aging process in general. Dietary associations with telomere length should be confirmed with adequately powered randomized controlled trials.