ABSTRACT
ABSTRACT Considering aging as a phenomenon in which there is a decline in essential processes for cell survival, we investigated the autophagic and proteasome pathways in three different groups: young, older and oldest old male adults. The expression profile of autophagic pathway-related genes was carried out in peripheral blood, and the proteasome quantification was performed in plasma. No significant changes were found in plasma proteasome concentrations or in correlations between proteasome concentrations and ages. However, some autophagy- and/or apoptosis-related genes were differentially expressed. In addition, the network and enrichment analysis showed an interaction between four of the five differentially expressed genes and an association of these genes with the transcriptional process. Considering that the oldest old individuals maintained both the expression of genes linked to the autophagic machinery, and the proteasome levels, when compared with the older group, we concluded that these factors could be considered crucial for successful aging.
RESUMO Considerando o envelhecimento como um fenômeno em que há um declínio nos processos essenciais a sobrevivência celular, investigamos as vias autofágica e proteassômica em três grupos: jovens, idosos e longevos. O perfil de expressão dos genes relacionados à via autofágica foi analisado em sangue periférico, e a quantificação do proteassoma realizada em plasma. Não foram encontradas alterações significativas nas concentrações plasmáticas de proteassoma ou na correlação entre as concentrações de proteassoma e as idades. No entanto, alguns genes relacionados a autofagia e / ou apoptose foram expressos diferencialmente. Além disso, as análises de rede e de enriquecimento mostraram uma interação entre quatro dos cinco genes diferencialmente expressos e a associação desses ao processo transcricional. Considerando que os indivíduos longevos mantiveram tanto a expressão de genes ligados à maquinaria autofágica, quanto os níveis de proteassoma quando comparados aos idosos, concluímos que esses fatores poderiam ser considerados cruciais para o envelhecimento bem-sucedido.
Subject(s)
Humans , Male , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Autophagy/genetics , Aging/genetics , Aging/metabolism , Longevity/genetics , Autophagy/physiology , Brazil , Gene Expression Regulation , Apoptosis/genetics , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/metabolism , Longevity/physiologyABSTRACT
Abstract Psychiatric disorders are highly prevalent all over the world with a great impact on public health. Altered homocysteine metabolism is implicated in the pathogenesis of many of these disorders, as it can interfere in normal methylation of subcellular components, promote neuroexcitotoxicity, and induce oxidative stress and inflammation. There are cumulative data implicating these mechanisms in the development of autism, schizophrenia, depression, bipolar disorder, and Alzheimer disease. Altered homocysteine metabolism is multifactorial in its origin. On one hand, genetic factors act as predisposing factors through brain development and function, and on the other hand, environmental factors give the opportunity for nutritional interventions improving metabolic status and possibly also clinical parameters. This article provides a review on the association of 1-carbon metabolism and autism, schizophrenia, depression, bipolar disorder, and dementia and goes through studies on the role of different cofactors and metabolites involved in this pathway.
ABSTRACT
BACKGROUND: Polymorphism of the gene for apolipoprotein E (APOE) is an important risk factor for the development of Alzheimer's disease. The ε4 allele of the APOE gene has been linked with a number of neuropsychiatric illnesses, and also with stress and depression among geriatric populations. OBJECTIVE: To identify APOE-ε4 polymorphism and correlate this with cognitive deficit among the elderly population of the island of Fernando de Noronha. METHOD: Neuropsychiatric tests (mini-mental state examination, verbal fluency test and clock drawing test) were applied to 52 elderly people without Alzheimer's disease. DNA was isolated from peripheral blood and genotyping of APOE was done by the PCR-RFLP method. RESULTS: 87 percent of the elderly population (mean age 69.6±7.0) had cognitive deficit. CONCLUSION: The observed frequency of the ε4 allele was 10 percent, but the correlation between the presence of ε4 and cognitive deficit in this population was not statistically significant.
INTRODUÇÃO: Polimorfismos no gene da apoliproteína E (APOE) são importantes fatores de risco para o desenvolvimento da doença de Alzheimer (DA). O alelo ε4 do gene APOE tem sido relacionado com declínio cognitivo e algumas doenças neuropsiquiátricas, primariamente a doença de Alzheimer. OBJETIVO: Identificar os polimorfismos de APOE-ε4 e relacionar com deficit cognitivo na população idosa da ilha de Fernando de Noronha. MÉTODO: Foram aplicados testes neuropsiquiátricos (mini exame do estado mental, teste de fluência verbal e teste do relógio) em 52 idosos sem DA. O DNA foi isolado do sangue periférico e a genotipagem de APOE foi realizada por PCR-RFLP. RESULTADOS: 87 por cento da população idosa com idade média de 69.6±7.0 apresentou déficit cognitivo. Foi observada uma freqüência de 10 por cento do alelo ε4. CONCLUSÃO: Não foi encontrada significância estatística quando relacionada a presença deste alelo e déficit cognitivo nos idosos avaliados.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , /genetics , Cognition Disorders/genetics , Polymorphism, Genetic , Age Factors , Alleles , Analysis of Variance , Alzheimer Disease/diagnosis , Alzheimer Disease/genetics , Brief Psychiatric Rating Scale , Brazil/epidemiology , Chi-Square Distribution , Cognition Disorders/epidemiology , Cognition Disorders/psychology , Cognition/physiology , Educational Status , Genotype , Geriatric Assessment , Neuropsychological Tests , Sex FactorsABSTRACT
OBJECTIVE: To investigate the association between total plasma homocysteine concentration, C677T and A1298C polymorphisms in MTHFR gene and Alzheimer's disease (AD) development. METHOD: Forty-three patients with probable (63 percent) and possible (37 percent) AD and 50 non-demented controls were evaluated. Groups did not differ as to gender, age, scholar years, diabetes, alcohol and coffee intake and physical activity. Total plasma homocysteine (Hcy) levels were determined by HPLC and genotyping for MTHFR by PCR/RFLP. Mann-Whitney "U" test was used to compare quantitative variable, Fisher-Freeman-Halton test to compare genotypes and allele proportions and Chi-square test to other qualitative variables. RESULTS: AD patients presented higher total plasma Hcy levels than controls and the difference was statistically significant. No differences in the C677T and A1298C MTHFR polymorphisms distributions were found between patients and controls. Plasma homocysteine concentration did not change with MTHFR genotypes. CONCLUSION: Our data confirms the association between increased plasma Hcy concentration and AD and suggests that neither C677T nor A1298C MTHFR polymorphisms contributed to genetic susceptibility for AD in elderly individuals in the Northeast of Brazil.
OBJETIVO: Investigar a associação entre a concentração plasmática total de homocisteína (Hcy), os polimorfismos C677T e A1298C do gene MTHFR e o desenvolvimento da Doença de Alzheimer (AD). MÉTODO: Foram avaliados 43 pacientes com doença de Alzheimer possível (37 por cento) e provável (63 por cento) e 50 controles não dementes, não divergentes quanto ao sexo, idade, anos de escolaridade, diabetes, consumo de álcool e de café e vida sedentária. Os níveis plasmáticos de homocisteína foram determinados por HPLC e a genotipagem para MTHFR por PCR/RFLP. A comparação dos níveis de homocisteína foi realizada pelo teste "U" Mann-Whitney, a comparação das proporções dos genótipos e alelos pelo teste de Fisher-Freeman-Halton e as demais variáveis qualitativas, pelo teste do qui-quadrado. RESULTADOS: Os pacientes AD apresentaram níveis mais elevados de Hcy plamática total do que os controles e a diferença entre os grupos foi estatisticamente significante. Não houve diferença nas distribuições genotípicas C677T e A1298C entre pacientes e controles. A concentração de Hcy não variou com os genótipos. CONCLUSÃO: Nossos dados confirmam a associação de concentração elevada de Hcy plasmática com DA e sugerem que os polimorfismos C677T e A1209C não contribuem para a susceptibilidade genética a DA em idosos do Nordeste do Brasil.