Aging and the brain: Biological and psychological mediators of atrophy and the ameliorative effect of calorie restriction in aged rhesus monkeys.

다국어 초록 (Multilingual Abstract)

The aging of the American population, accompanied by an increased incidence of chronic physical and neural disease states, will have a substantially negative impact on the long-term solvency of the economy. Although the prodromal dysregulation of physiological systems related to aging is clear, there is a paucity of research examining how these changes differentially impact the macro- and microstructural integrity of the aged brain. Psychological responsiveness to stress also appears to be an important correlate of age-related atrophy and is related to greater risk for dementia. All of these factors are able to induce atrophy by triggering oxidative stress. Furthermore, it is equally critical and complementary to investigate the impact of a therapeutic intervention that could reduce or mitigate the influence of these factors on age-related atrophy of the brain. Aged rhesus monkeys (Macaca mulatta) were used as an animal model of human aging. The monkeys were either fed normal or 30% calorie restriction (CR) relative to baseline intake diets. Biomarkers related to neuroinflammation, cerebrovascular health and metal ion accumulation in brain were considered, as well as an index of stress reactivity to different environments. Each of these factors was differentially related to regional and global atrophy for both volume and microstructure. Importantly, CR improved both physiological and psychological function and conferred substantial protection to the brain. Calorie restriction or CR mimetics may be important for improving the structure and function of the brain in old age.