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1.
Biodemography Soc Biol ; 69(2): 57-74, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38551453

RESUMO

Biomarkers in population health research serve as indicators of incremental physiological deterioration and contribute to our understanding of mechanisms through which social disparities in health unfold over time. Yet, few population-based studies incorporate biomarkers of aging in early midlife, when disease risks may emerge and progress across the life course. We describe the distributions of several biomarkers of inflammation and neurodegeneration and their variation by sociodemographic characteristics using blood samples collected during Wave V of the National Longitudinal Study of Adolescent to Adult Health (ages 33-44 years). Higher mean levels of inflammatory and neurodegenerative biomarkers were associated with greater socioeconomic disadvantage. For example, the neurodegenerative markers, Neurofilament Light Chain and total Tau proteins were higher among lower income groups, though the relationship was not statistically significant. Similarly, proinflammatory marker Tumor Necrosis Factor-α (TNF-α) levels were higher among those with lower education. Significant differences in the mean levels of other proinflammatory markers were observed by race/ethnicity, sex, census region, BMI, and smoking status. These descriptive findings indicate that disparities in biomarkers associated with aging are already evident among young adults in their 30s and attention should focus on age-related disease risk earlier in the life course.


Assuntos
Envelhecimento , Biomarcadores , Humanos , Biomarcadores/sangue , Biomarcadores/análise , Feminino , Masculino , Adulto , Envelhecimento/sangue , Envelhecimento/fisiologia , Estudos Longitudinais , Inflamação/sangue , Estudos de Coortes , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/análise , Adolescente , Fatores Socioeconômicos , Fatores Sociodemográficos
2.
Aging (Albany NY) ; 13(16): 20029-20049, 2021 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-34456185

RESUMO

INTRODUCTION: Despite associated with multiple geriatric disorders, whether housing type, an indicator of socioeconomic status (SES) and environmental factors, is associated with accelerated biological aging is unknown. Furthermore, although individuals with low-SES have higher body mass index (BMI) and are more likely to smoke, whether BMI and smoking status moderate the association between SES and biological aging is unclear. We examined these questions in urbanized low-SES older community-dwelling adults. METHODS: First, we analyzed complete blood count data using the cox proportional hazards model and derived measures for biological age (BA) and biological age acceleration (BAA, the higher the more accelerated aging) (N = 376). Subsequently, BAA was regressed on housing type, controlling for covariates, including four other SES indicators. Interaction terms between housing type and BMI/smoking status were separately added to examine their moderating effects. Total sample and sex-stratified analyses were performed. RESULTS: There were significant differences between men and women in housing type and BAA. Compared to residents in ≥3 room public or private housing, older adults resided in 1-2 room public housing had a higher BAA. Furthermore, BMI attenuated the association between housing type and BAA. In sex-stratified analyses, the main and interaction effects were only significant in women. In men, smoking status instead aggravated the association between housing type and BAA. CONCLUSION: Controlling for other SES indicators, housing type is an independent socio-environmental determinant of BA and BAA in a low-SES urbanized population. There were also sex differences in the moderating effects of health behaviors on biological aging.


Assuntos
Envelhecimento/psicologia , Comportamentos Relacionados com a Saúde , Habitação , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Índice de Massa Corporal , Feminino , Habitação/economia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Classe Social
3.
Sci Rep ; 11(1): 12629, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135381

RESUMO

Imbalanced nutrition is associated with accelerated ageing, possibly mediated by microbiota. An analysis of the circulatory microbiota obtained from the leukocytes of participants in the MRC Twenty-07 general population cohort was performed. We now report that in this cohort, the most biologically aged exhibit a significantly higher abundance of circulatory pathogenic bacteria, including Neisseria, Rothia and Porphyromonas, while those less biologically aged possess more circulatory salutogenic (defined as being supportive of human health and wellbeing) bacteria, including Lactobacillus, Lachnospiraceae UCG-004 and Kocuria. The presence of these salutogenic bactreria is consistent with a capacity to metabolise and produce Nrf2 agonists. We also demonstrate that associated one carbon metabolism, notably betaine levels, did not vary with chronological age, but displayed a difference with socioeconomic position (SEP). Those at lower SEP possessed significantly lower betaine levels indicative of a poorer diet and poorer health span and consistent with reduced global DNA methylation levels in this group. Our data suggest a clear route to improving age related health and resilience based on dietary modulation of the microbiota.


Assuntos
Envelhecimento/sangue , Bactérias/classificação , Betaína/sangue , Análise de Sequência de DNA/métodos , Adulto , Idoso , Bactérias/genética , Bactérias/isolamento & purificação , Feminino , Humanos , Estilo de Vida , Masculino , Metilaminas , Pessoa de Meia-Idade , Filogenia , Estudos Prospectivos , RNA Ribossômico 16S/genética , Fatores Socioeconômicos
4.
Commun Biol ; 4(1): 271, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654170

RESUMO

Red blood cells (RBCs) capability to deliver oxygen (O2) has been routinely measured by P50. Although this defines the ability of RBCs to carry O2 under equilibrium states, it cannot determine the efficacy of O2 delivery in dynamic blood flow. Here, we developed a microfluidic analytical platform (MAP) that isolates single RBCs for assessing transient changes in their O2 release rate. We found that in vivo (biological) and in vitro (blood storage) aging of RBC could lead to an increase in the O2 release rate, despite a decrease in P50. Rejuvenation of stored RBCs (Day 42), though increased the P50, failed to restore the O2 release rate to basal level (Day 0). The temporal dimension provided at the single-cell level by MAP could shed new insights into the dynamics of O2 delivery in both physiological and pathological conditions.


Assuntos
Envelhecimento/sangue , Eritrócitos/metabolismo , Técnicas Analíticas Microfluídicas , Oxigênio/sangue , Análise de Célula Única , Adulto , Fatores Etários , Difusão , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
5.
J Gerontol B Psychol Sci Soc Sci ; 76(3): 583-595, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-32064519

RESUMO

OBJECTIVES: To clarify the relationships among race, gender, and socioeconomic status (SES) with C-reactive protein (CRP). METHOD: The present study analyzed data from 6,521 Black and White respondents aged 51 and older in the Health and Retirement Study, a nationally representative sample of midlife and older adults, to address two aims. We sought to (i) assess the independent associations between race, gender, and SES with CRP concentrations and (ii) test whether race, gender, and SES interacted to produce unequal CRP concentrations cross-sectionally and over a 4-year follow-up. RESULTS: The results demonstrated that race, gender, and SES were each independently associated with baseline CRP, but only SES was associated with CRP at follow-up. Furthermore, race, gender, and education interacted to produce differential CRP levels at baseline. There were incremental benefits for each additional level of education for White men and women, but the relationship between education and CRP was more complicated for Black men and women. Compared with other race/gender groups with less than high school, Black women had the highest and Black men had the lowest levels of CRP. There were no apparent benefits to CRP for Black women with college compared with Black women with high school, while Black men with less than high school and college had similar concentrations of CRP. DISCUSSION: In clarifying the complexity inherent in CRP disparities, this work contributes to a greater understanding of the biological mechanisms underlying racial disparities in leading causes of morbidity and mortality in the United States.


Assuntos
Envelhecimento , População Negra/estatística & dados numéricos , Proteína C-Reativa/análise , Escolaridade , Disparidades nos Níveis de Saúde , Classe Social , População Branca/estatística & dados numéricos , Idoso , Envelhecimento/sangue , Envelhecimento/etnologia , Envelhecimento/psicologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Determinantes Sociais da Saúde/etnologia , Estados Unidos/epidemiologia
6.
Genes (Basel) ; 11(6)2020 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-32580526

RESUMO

Epigenetic aging (EA) indices are frequently used as predictors of mortality and other important health outcomes. However, each of the commonly used array-based indices has significant heritable components which could tag ethnicity and potentially confound comparisons across racial and ethnic groups. To determine if this was possible, we examined the relationship of DNA methylation in cord blood from 203 newborns (112 African American (AA) and 91 White) at the 513 probes from the Levine PhenoAge Epigenetic Aging index to ethnicity. Then, we examined all sites significantly associated with race in the newborn sample to determine if they were also associated with an index of ethnic genetic heritage in a cohort of 505 AA adults. After Bonferroni correction, methylation at 50 CpG sites was significantly associated with ethnicity in the newborn cohort. The five most significant sites predicted ancestry with a receiver operator characteristic area under the curve of 0.97. Examination of the top 50 sites in the AA adult cohort showed that methylation status at 11 of those sites was also associated with percentage European ancestry. We conclude that the Levine PhenoAge Index is influenced by cryptic ethnic-specific genetic influences. This influence may extend to similarly constructed EA indices and bias cross-race comparisons.


Assuntos
Envelhecimento/genética , Metilação de DNA/genética , Epigênese Genética/genética , Negro ou Afro-Americano/genética , Envelhecimento/sangue , Etnicidade/genética , Feminino , Sangue Fetal/metabolismo , Hispânico ou Latino/genética , Humanos , Recém-Nascido , Masculino , População Branca/genética
7.
Artigo em Inglês | MEDLINE | ID: mdl-32243999

RESUMO

This paper reviews the prevalence, implications, prevention and management of antipsychotic-induced hyperprolactinemia in aging populations. Antipsychotics are indicated mainly for the treatment of psychotic illness but are also used in other conditions. Complications induced by antipsychotics increase with age, due to age-related changes in drug metabolism and excretion. Almost all antipsychotics lead to hyperprolactinemia by blocking dopamine D2 receptors in the anterior pituitary gland, which counteracts dopamine's inhibitory action on prolactin secretion. The main findings of this narrative review are that, though many of the known side effects of high prolactin levels lose their salience with age, the risk of exacerbating osteoporosis remains critical. Methods of preventing antipsychotic-induced hyperprolactinemia in older individuals include using antipsychotic medication (AP) as sparingly as possible and monitoring AP serum levels, regularly measuring prolactin levels, closely monitoring bone density, treating substance abuse, and teaching patients stress management techniques. When hyperprolactinemia symptoms cannot be otherwise managed, adjunctive drugs are available. Potential helpful adjuncts are: dopamine agonists, antipsychotics with partial agonist properties (e.g. aripiprazole), selective estrogen receptor modulators, and metformin. Because a gold standard for prevention/treatment has not been established, clinical decisions need to be made based on safety and individual circumstance.


Assuntos
Envelhecimento/efeitos dos fármacos , Antipsicóticos/efeitos adversos , Gerenciamento Clínico , Hiperprolactinemia/induzido quimicamente , Hiperprolactinemia/epidemiologia , Envelhecimento/sangue , Antagonistas dos Receptores de Dopamina D2/efeitos adversos , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/prevenção & controle , Prevalência , Prolactina/sangue
8.
Methods Mol Biol ; 2138: 207-216, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32219750

RESUMO

Nicotinamide adenine dinucleotide (NAD+) and its related metabolites (NADome) are important endogenous analytes that are thought to play important roles in cellular metabolism, inflammation, oxidative stress, cancer, neurodegeneration, and aging in mammals. However, these analytes are unstable during the collection of biological fluids, which is a major limiting factor for their quantitation. Herein, we describe a highly robust and quantitative method using liquid chromatography coupled to tandem mass spectrometry to quantify the NADome in whole blood, plasma, mononuclear cells, platelets, cerebrospinal fluid (CSF), and urine. This methodology represents a "gold standard" of measure for understanding biological pathways and developing targeted pharmacological interventions to modulate NAD+ biosynthesis and NAD-dependent mediators in health and disease.


Assuntos
Envelhecimento/metabolismo , Biomarcadores/metabolismo , Cromatografia Líquida/métodos , Envelhecimento Saudável/metabolismo , NAD/metabolismo , Espectrometria de Massas em Tandem/métodos , Envelhecimento/sangue , Envelhecimento/urina , Biomarcadores/sangue , Biomarcadores/urina , Plaquetas/metabolismo , Células Cultivadas , Líquido Cefalorraquidiano/metabolismo , Estudos de Avaliação como Assunto , Envelhecimento Saudável/sangue , Envelhecimento Saudável/urina , Humanos , Inflamação/sangue , Inflamação/metabolismo , Inflamação/urina , Leucócitos Mononucleares/metabolismo , NAD/sangue , NAD/urina , Estresse Oxidativo/fisiologia , Urina/química
9.
J Gerontol A Biol Sci Med Sci ; 75(3): 473-480, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31630168

RESUMO

Methylation levels measured at defined sites across the genome have recently been shown to be correlated with an individual's chronological age. Age acceleration, or the difference between age estimated from DNA methylation status and chronological age, has been proposed as a novel biomarker of aging. In this study, the cross-sectional association between two different measures of age acceleration and cognitive function was investigated using whole blood samples from 2,157 African American participants 47-70 years of age in the population-based Atherosclerosis Risk in Communities (ARIC) Study. Cognition was evaluated using three domain-specific tests. A significant inverse association between a 1-year increase in age acceleration calculated using a blood-based age predictor and scores on the Word Fluency Test was found using a general linear model adjusted for chronological age, gender, and years of education (ß = -0.140 words; p = .001) and after adding other potential confounding variables (ß = -0.104 words, p = .023). The results were replicated in 1,670 European participants in the Generation Scotland: Scottish Family Health Study (fully adjusted model: ß = -0.199 words; p = .034). A significant association was also identified in a trans-ethnic meta-analysis across cohorts that included an additional 708 European American ARIC study participants (fully adjusted model: ß = -0.110 words, p = .003). There were no associations found using an estimate of age acceleration derived from multiple tissues. These findings provide evidence that age acceleration is a correlate of performance on a test of verbal fluency in middle-aged adults.


Assuntos
Envelhecimento/genética , Negro ou Afro-Americano/genética , Negro ou Afro-Americano/psicologia , Cognição , Epigênese Genética , Idoso , Envelhecimento/sangue , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/genética , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Tempo
10.
Nutrients ; 11(10)2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31590434

RESUMO

BACKGROUND: The association between circulating levels of vitamin D and the incidence of chronic diseases is known. The identification of vitamin D as a biomarker of physiological/pathological ageing could contribute to expanding current knowledge of its involvement in healthy ageing. METHODS: According to PRISMA guidelines, a systematic review was conducted on cohorts studying the role of 25OH-Vitamin D [25(OH)D] and 1,25(OH)2-Vitamin D [1,25(OH)2D] concentrations as biomarkers of healthy ageing. We consulted MedLine, Scopus, and Web of Science to search for studies on the association between vitamin D status in populations of originally healthy adults, and outcomes of longevity, illness, and physical and cognitive functionality. The quality of the studies was assessed using the Newcastle Ottawa scale. RESULTS: Twenty cohorts from 24 articles were selected for this review. Inverse associations were found between low 25(OH)D levels and all-cause mortality, respiratory and cardiovascular events, as well as markers relating to hip and non-vertebral fractures. Associations between 1,25(OH)2D and healthy ageing outcomes gave similar results, although of lower clinical significance. CONCLUSIONS: This systematic review pinpoints peculiar aspects of vitamin D as a multidimensional predictor of ill health in the ageing process. Further well-designed controlled trials to investigate whether vitamin D supplement results in superior outcomes are warranted in the future.


Assuntos
Envelhecimento/sangue , Indicadores Básicos de Saúde , Deficiência de Vitamina D/sangue , Vitamina D/análogos & derivados , Fatores Etários , Biomarcadores/sangue , Causas de Morte , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/mortalidade
11.
Clin Chem Lab Med ; 58(1): 69-76, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31377731

RESUMO

Background Monthly medians of patient results are useful in assessment of analytical quality in medical laboratories. Separate medians by gender makes it possible to generate two independent estimates of contemporaneous errors. However, for plasma creatinine, reference intervals (RIs) are different by gender and also higher over 70 years of age. Methods Daily, weekly and monthly patient medians were calculated from the raw data of plasma creatinine concentrations for males between 18 and 70 years, males >70 years, females between 18 and 70 years and females >70 years. Results The medians of the four groups were all closely associated, with similar patterns. The mean of percentage bias from each group defined the best estimate of bias. The maximum half-range (%) of the bias evaluations provided an estimate of the uncertainty comparable to the analytical performance specifications: thus, bias estimates could be classified as optimum, desirable or minimum quality. Conclusions Medians by gender and age are useful in assessment of analytical stability for plasma creatinine concentration ranging from 60 to 90 µmol/L. The daily medians are valuable in rapid detection of large systematic errors, the weekly medians in detecting minor systematic errors and monthly medians in assessment of long-term analytical stability.


Assuntos
Envelhecimento/sangue , Análise Química do Sangue/métodos , Creatinina/sangue , Caracteres Sexuais , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
12.
J Health Soc Behav ; 60(3): 291-308, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31409156

RESUMO

The present study extends prior research on the links between social adversity and aging by employing more comprehensive measures of adversity and a new gene expression index of aging. Hierarchical regression and 20 years of data from a sample of 381 black Americans were used to test models regarding the impact of social adversity on speed of aging. Consistent with the early life sensitivity model, early adversity continued to predict accelerated aging after controlling for adult adversity. Contrary to the pathway model, adult adversity was not related to aging following controls for early adversity. The cumulative stress model received partial support as high adversity during adulthood amplified the effect of early adversity on aging. Finally, consonant with the social change model, low adversity during adulthood buffered the effect of early adversity on aging. These findings held after controlling for health behaviors such as smoking, diet, and exercise.


Assuntos
Envelhecimento , Estresse Psicológico , Adolescente , Adulto , Negro ou Afro-Americano , Envelhecimento/sangue , Envelhecimento/fisiologia , Envelhecimento/psicologia , Bases de Dados Factuais , Feminino , Georgia , Disparidades nos Níveis de Saúde , Humanos , Iowa , Masculino , Análise de Regressão , Resiliência Psicológica
13.
Lipids ; 54(5): 321-328, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31087416

RESUMO

While there is considerable evidence supporting health benefits of consuming diets high in omega-3 (n-3) fatty acids, there is no quick and effective tool to measure n-3 intake. The objective of this study was to evaluate the accuracy of a rapid assessment questionnaire (the Omega-3 Checklist) used to quantify intake of n-3 fatty acids. This was done by comparing n-3 intakes to blood biomarkers of n-3 exposure in a population of healthy men and women. In addition, a separate analysis was run including covariates age, sex, and weight, which have been shown to affect n-3 biomarker levels. Reported intake of eicosapentaenoic acid (EPA), docoshexaenoic acid (DHA), and EPA + DHA was correlated with erythrocyte EPA (Spearman's rank correlation rs = 0.51, p < 0.001), DHA (rs = 0.54, p < 0.001), and the Omega-3 Index (rs = 0.57, p < 0.001). These associations remained significant when controlling for age, sex, and weight. Therefore, the Omega-3 Checklist can be a useful, rapid assessment tool to estimate individuals' EPA and DHA intake.


Assuntos
Inquéritos sobre Dietas/normas , Dieta , Ácidos Graxos Ômega-3/administração & dosagem , Adulto , Envelhecimento/sangue , Biomarcadores/sangue , Peso Corporal , Lista de Checagem , Eritrócitos/química , Ácidos Graxos Ômega-3/sangue , Feminino , Humanos , Masculino , Caracteres Sexuais
14.
J Nutr Health Aging ; 23(5): 479-482, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31021366

RESUMO

BACKGROUND: Population aging is an important problem worldwide, with activity and quality of daily living commonly reduced in elderly people. leading to increased hospitalization and mortality rates, and substantial individual and social burdens. OBJECTIVE: This study was designed to investigate the associations of serum homocysteine levels with activity and quality of daily living in Chinese centenarians for the first time. PARTICIPANTS: The China Hainan Centenarian Cohort Study was performed in 18 cities and counties of Hainan Province. MAIN MEASURES: Home interview, physical examination and blood analysis were performed in 787 centenarians following standard procedures. KEY RESULTS: The median age was 102 years, ranging between 100 and 115 years. There were 634 females (80.6%) and 153 males (19.4%) in all. The median level of serum homocysteine was 23.80 (18.80-29.90) umol/L, whereas median values of Barthel Index and EuroQol 5 Dimensions were 85(60-95) and 0.661(0.558-0.766), respectively. The centenarians with serum homocysteine levels ≥23.8µmol/L were more likely to had lower values of Barthel Index and EuroQol 5 Dimensions than those with serum homocysteine levels <23.8µmol/L (P<0.05 for all). In multivariate linear regression analyses, serum homocysteine levels were significantly associated with Barthel Index and EuroQol 5 Dimensions (P<0.05 for all). CONCLUSIONS: Serum homocysteine levels had important associations with activity and quality of daily living in Chinese centenarians. Future research should focus on the value of intervening in serum homocysteine levels by supplying folic acid (vitamin B9) and vitamin B12 on improving activity and quality of daily living in elderly people.


Assuntos
Atividades Cotidianas/psicologia , Envelhecimento/sangue , Homocisteína/sangue , Qualidade de Vida/psicologia , Idoso de 80 Anos ou mais , Povo Asiático , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino
15.
Clin Pharmacokinet ; 58(6): 793-803, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30607889

RESUMO

BACKGROUND AND OBJECTIVE: Milrinone is used for the prevention of low cardiac output syndrome in pediatric patients after cardiac surgery. Milrinone is mainly eliminated by the kidneys; however, there is limited information on milrinone pharmacokinetics in infants who have acute kidney injury (AKI). The aim of this study was to develop a milrinone population pharmacokinetic model in neonates and infants with or without AKI. The developed milrinone pharmacokinetic model was utilized for a Monte Carlo simulation analysis to identify age-appropriate dosing regimens in neonates and infants. METHODS: Population pharmacokinetic analysis was performed with a total of 1088 serum milrinone concentrations obtained from 92 infants as part of a prospective clinical study in neonates and infants following cardiac surgery (ClinicalTrials.gov identifier NCT01966237). AKI stages were determined based on the Kidney Injury Improving Global Outcomes (KDIGO) Clinical Practice Guideline within the first three postoperative days. RESULTS: A two-compartment model was found to adequately describe the pharmacokinetic data. Allometrically scaled body weight, AKI stages, and maturation function were identified as significant predictors of milrinone clearance. The proposed dosing regimens for milrinone continuous infusions were determined based on a target concentration attainment of simulated steady-state concentration and covered three age groups across 0-12 months of age for each AKI stage. CONCLUSION: This study provides a milrinone population pharmacokinetic model in neonates and infants and captures the developmental changes in clearance. Age-appropriate dosing regimens were determined based on the simulation analysis with the developed pharmacokinetic model. The findings will facilitate model-informed precision dosing of milrinone in infants with or without AKI.


Assuntos
Injúria Renal Aguda/sangue , Envelhecimento/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Milrinona/farmacocinética , Inibidores da Fosfodiesterase 3/farmacocinética , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Peso Corporal , Baixo Débito Cardíaco/sangue , Baixo Débito Cardíaco/etiologia , Baixo Débito Cardíaco/prevenção & controle , Relação Dose-Resposta a Droga , Humanos , Lactente , Recém-Nascido , Taxa de Depuração Metabólica , Milrinona/administração & dosagem , Milrinona/sangue , Milrinona/uso terapêutico , Modelos Biológicos , Método de Monte Carlo , Inibidores da Fosfodiesterase 3/administração & dosagem , Inibidores da Fosfodiesterase 3/sangue , Inibidores da Fosfodiesterase 3/uso terapêutico , Estudos Prospectivos
16.
Eur J Epidemiol ; 34(2): 191-209, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30421322

RESUMO

To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n = 1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5 years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.


Assuntos
Envelhecimento , Avaliação Geriátrica/métodos , Serviços de Saúde para Idosos , Idoso , Envelhecimento/sangue , Envelhecimento/genética , Envelhecimento/metabolismo , Envelhecimento/psicologia , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Projetos de Pesquisa , Suécia/epidemiologia
17.
Curr Aging Sci ; 11(3): 182-194, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30338748

RESUMO

BACKGROUND: Cognitive frailty emerges as one of the threats to healthy aging. It is in continuum with advancing of age with uncertain indicator between pathological and physiological changes. Alterations in pathways associated with the aging process have been observed including oxidative stress, lipid metabolism, and inflammation. However, the exact mechanisms leading to cognitive decline are still unclear. OBJECTIVE: This study was sought to assess the level of cognitive functions and linked with blood oxidative status during normal aging in rats. METHODS: A longitudinal study using male Sprague Dawley rats was performed starting from the age of 14 months old to 27 months old. Cognitive functions tests such as open field, Morris water maze and object recognition were determined at the age of 14, 18, 23, and 27 months old and were compared with group 3 months old. Blood was collected from the orbital venous sinus and oxidative status was determined by measuring the level of DNA damage, lipid peroxidation, protein oxidation and antioxidant enzymes activity. RESULTS: Aged rats showed declining exploratory behavior and increased in the level of anxiety as compared to the young rats. The level of DNA damage increased with increasing age. Interestingly, our study found that both levels of malondialdehyde and plasma carbonyl content decreased with age. In addition, the level of superoxide dismutase activity was significantly decreased with age whereas catalase activity was significantly increased from 18 months of age. However, no significant difference was found in glutathione peroxidase activity among all age groups. CONCLUSION: The progressions of cognitive impairment in normal aging rats are linked to the increment in the level of DNA damage.


Assuntos
Envelhecimento/sangue , Envelhecimento/psicologia , Comportamento Animal , Cognição , Estresse Oxidativo , Fatores Etários , Animais , Ansiedade/sangue , Ansiedade/psicologia , Biomarcadores/sangue , Catalase/sangue , Dano ao DNA , Comportamento Exploratório , Peroxidação de Lipídeos , Masculino , Malondialdeído/sangue , Aprendizagem em Labirinto , Atividade Motora , Carbonilação Proteica , Ratos Sprague-Dawley , Reconhecimento Psicológico , Superóxido Dismutase/sangue
18.
Clin Pharmacol Drug Dev ; 7(8): 920-926, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30144296

RESUMO

Bazedoxifene (BZA), a chemically distinct selective estrogen receptor modulator, has demonstrated efficacy and long-term safety in phase 3 placebo-controlled studies for prevention and treatment of osteoporosis. Here, we assessed the potential effects of age and renal function on BZA pharmacokinetics in healthy postmenopausal women (aged 55-84 years; CLcr, 32-109 mL/min). This was an open-label, single-dose, parallel, nonrandomized inpatient study conducted in healthy postmenopausal women and postmenopausal women with impaired renal function. Each subject received a single oral dose of BZA in a 20-mg tablet. Twenty-six subjects were enrolled: 8 in each of 3 age groups (55-64 years, 65-74 years, ≥75 years) and 2 (aged 71 and 75 years) with mild renal impairment; all subjects received treatment and completed the study. Age-related changes in pharmacokinetics were apparent. Although the correlation was modest (R2 = 0.28), BZA CL/F decreased steadily with age, such that the oldest group (>75 years) had a mean CL/F 60% less than the youngest group (55-64 years). Over the observed range of CLcr, there was a weak positive correlation (R2 = 0.19) between BZA CL/F and CLcr.


Assuntos
Envelhecimento/fisiologia , Indóis/farmacocinética , Rim/fisiologia , Rim/fisiopatologia , Pós-Menopausa , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Feminino , Humanos , Indóis/sangue , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Insuficiência Renal/sangue , Insuficiência Renal/fisiopatologia , Moduladores Seletivos de Receptor Estrogênico/farmacocinética
19.
J Physiol Pharmacol ; 69(1): 75-81, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29769423

RESUMO

Anemia is an independent risk factor for functional decline and mortality among older adults. Since mild anemia in older people is often under-diagnosed and ignored, its prevalence needs precise determination and recognition of predisposing factors. None of the previous studies based on the data obtained from the representative elderly population identified the influence of socio-economic factors on the prevalence of anemia. PolSenior was a cross-sectional population-based study performed on the nationally representative sample of Polish seniors. Complete blood count was assessed in 4003 respondents aged 65 years or above (1910 women) divided into six five-year cohorts and a reference group of 622 people aged 55 - 59 years (333 women). Anemia was defined based on the WHO criteria: Hb < 12.0 g/dL in women and Hb < 13.0 g/dL in men. The following socio-economic factors were evaluated through the multiple logistic regression analysis: education level, marital status, place of residence, living arrangements and self-reported poverty. The prevalence of anemia in older persons standardized for the population was 10.8% (17.4% of the study group) and was more frequent in men than in women (20.8% versus 13.6%). The frequency of anemia progressed with age from 5.3% in the youngest to 37.7% in the oldest cohort, and the progression was higher in men. The multiple logistic regression analysis revealed the link between anemia and age in both genders, as well as unmarried status and urban dwelling in men. When age was not taken into account, logistic regression showed the link between anemia and unmarried status, urban place of residence (both genders), and low level of education (women only). Among seniors, those poorly educated, unmarried and city inhabitants require intense screening for anemia.


Assuntos
Anemia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Feminino , Humanos , Masculino , Polônia/epidemiologia , Prevalência , Fatores Socioeconômicos
20.
Magn Reson Med ; 80(2): 521-528, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29271045

RESUMO

PURPOSE: To develop a non-contrast-agent MRI technique to quantify cerebral venous T2 in mice. METHODS: We implemented and optimized a T2 -relaxation-under-spin-tagging (TRUST) sequence on an 11.7 Tesla animal imaging system. A flow-sensitive-alternating-inversion-recovery (FAIR) module was used to generate control and label images, pair-wise subtraction of which yielded blood signals. Then, a T2 -preparation module was applied to produce T2 -weighted images, from which blood T2 was quantified. We conducted a series of technical studies to optimize the imaging slice position, inversion slab thickness, post-labeling delay (PLD), and repetition time. We also performed three physiological studies to examine the venous T2 dependence on hyperoxia (N = 4), anesthesia (N = 3), and brain aging (N = 5). RESULTS: Our technical studies suggested that, for efficient data acquisition with minimal bias in estimated T2 , a preferred TRUST protocol was to place the imaging slice at the confluence of sagittal sinuses with an inversion-slab thickness of 2.5-mm, a PLD of 1000 ms and a repetition time of 3.5 s. Venous T2 values under normoxia and hyperoxia (inhaling pure oxygen) were 26.9 ± 1.7 and 32.3 ± 2.2 ms, respectively. Moreover, standard isoflurane anesthesia resulted in a higher venous T2 compared with dexmedetomidine anesthesia (N = 3; P = 0.01) which is more commonly used in animal functional MRI studies to preserve brain function. Venous T2 exhibited a decrease with age (N = 5; P < 0.001). CONCLUSION: We have developed and optimized a noninvasive method to quantify cerebral venous blood T2 in mouse at 11.7 T. This method may prove useful in studies of brain physiology and pathophysiology in animal models. Magn Reson Med 80:521-528, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Assuntos
Envelhecimento , Encéfalo , Imageamento por Ressonância Magnética/métodos , Oximetria/métodos , Envelhecimento/sangue , Envelhecimento/fisiologia , Anestésicos/farmacologia , Animais , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Hiperóxia/sangue , Hiperóxia/diagnóstico por imagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Oxigênio/sangue
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