Amelioration of the autonomic imbalances of old age with exercise: exploring the molecular and physiological mechanisms

Resumo

There is considerable anecdotal evidence that a sedentary Iifestyle can lead to ill heath in old age, whereas physical activity has long-term health and wellbeing benefits. The reasons why homeostatic systems deteriorate in the elderly, and why exercise can ameliorate this deterioration, are not well understood. However, there is growing evidence that autonomic nervous system (ANS) imbalance is involved in a wide range of chronic conditions of old-age, such as hypertension. We hypothesize that the development and/or maintenance of the ANS imbalance is associated with changes in the expression of genes in the brain that, through their activity, form one or more functional networks can be influenced by both age and lifestyle factors, such as physical activity. In order to test this hypothesis, we will: i) identify putative gene networks by carrying out detailed and comprehensive transcriptome analysis on brain regions involved in the regulation of ANS of WKY rats compared to SHRs with a genetic predisposition to ANS imbalance characterized by over sympathetic activity related to gene expression changes as animals' age; iii) ask if gene expression is altered by physical exercise, initiated either before or after the onset of ANS imbalance; Iv) use bioinformatic tools to construct putative pathways and gene networks that may govern these processes to identify hub genes with many connections. Proof of principle studies will determine whether some of the age-related pathophysiology can be ameliorated. If so, these genes will undergo robust molecular, cellular and, physiological analysis that will reveal the roles of these hub genes in network stability and their response to external cues such as exercise. (AU)