Mecanismos moleculares associados ao declínio cognitivo, exercício físico, estado nutricional e desempenho funcional de idosos

Abstract

Cognitive decline in older adults may be associated with oxidative stress and chronic inflammation. In addition, inadequate nutritional status may contribute to cognitive decline and impaired functional performance in these individuals. However, exercise can improve cognitive functions and functional performance in this population. This thesis aimed to analyze the molecular mechanisms associated with cognitive impairment, their relationship with physical exercise, and the association of nutritional status with the functional status of older adults. The work was developed in three stages, resulting in three different products. In the first stage, through an in silico analysis using GeneCards and String databases, the mechanisms of glucose transport and their influence on the cognitive function of the older adults were demonstrated, including a hypothesis on how the interactions of the gene network related to peripheral hyperglycemia can lead to negative regulation of glucose transporters in the brain, especially through alterations in the expression of the SLC2A1 gene (related to GLUT 1), and their possible consequences due to progranulin polymorphism and hexokinase alterations. In the second stage, an in silico analysis was also performed using GeneCards and String databases, aiming to elucidate the molecular mechanisms by which exercise could reduce the risk of neurobiological complications resulting from hyperhomocysteinemia and consequently, Alzheimer's disease. Homocysteine reduces the synthesis and bioactivity of nitric oxide (NO) by endothelial cells, increasing oxidative stress and inflammatory reaction. Exercise, on the other hand, stimulates the release of NO by endothelial and skeletal muscle cells, contributing to the regulation of blood pressure and prevention of endothelial cell dysfunction. Finally, in the third stage, using the Mini Nutritional Assessment, Barthel Index, and Charlson Comorbidity Index, the associations between nutritional status, functional status, comorbidities, age, and gender were analyzed in older individuals who received home nursing care in Norway using path analysis. The main finding of this study is that the participants' functional status was directly associated with nutritional status (β = 0.32; p < 0.001), and comorbidities were indirectly associated with nutritional status (β = - 0.07; p < 0.017). The results of this study demonstrate the relationship between nutritional status, functional capacity, and comorbidities in older adults. Such information can be used to monitor the health and functionality of older individuals, as well as to develop specific interventions targeting each of these outcomes more effectively to improve the quality of life of these individuals.