Effects of aging and calorie restriction on white matter in rhesus macaques

Abstract

Rhesus macaques on a calorie restricted diet (CR) develop less age-related disease, have virtually no indication of diabetes, are protected against sarcopenia, and potentially live longer. Beneficial effects of caloric restriction likely include reductions in age-related inflammation and oxidative damage. Oligodendrocytes are particularly susceptible to inflammation and oxidative stress, therefore, we hypothesized that CR would have a beneficial effect on brain white matter and would attenuate age-related decline in this tissue. CR monkeys and controls underwent diffusion tensor imaging (DTI). A beneficial effect of CR indexed by DTI was observed in superior longitudinal fasciculus, fronto-occipital fasciculus, external capsule, and brainstem. Aging effects were observed in several regions, although CR appeared to attenuate age-related alterations in superior longitudinal fasciculus, frontal white matter, external capsule, right parahippocampal white matter, and dorsal occipital bundle. The results, however, were regionally specific and also suggested that CR is not salutary across all white matter. Further evaluation of this unique cohort of elderly primates to mortality will shed light on the ultimate benefits of an adult-onset, moderate CR diet for deferring brain aging.

Figure 1

White matter microstructure and age: calorie restricted and control monkeys combined. There was a negative correlation between fractional anisotropy (FA) and age. There was a positive correlation between mean diffusivity (MD) and age. FA is shown on the top, and MD is shown below. The color in the images represents the magnitude of the t statistic.

Figure 2

The calorie restricted (CR) animals showed several regions of greater fractional anisotropy (FA) and lower mean diffusivity (MD) compared to controls. The cooler colors (green) indicate regions where the CR animals showed lower MD compared to controls. Hot colors (orange/red) indicate regions where the CR animals showed higher FA compared to Controls. The color in the images represents the magnitude of the t statistic.

Figure 3

In some regions, the control group showed greater fractional anisotropy (FA) and lower mean diffusivity (MD) compared to the calorie restricted (CR) animals. Regions indicated by blue scale color are regions where the control group showed less MD compared to controls. Regions indicated by red scale colors are those where the control group showed higher FA compared to controls. The color in the images represents the magnitude of the t statistic.

Figure 4

Interaction with age. Both calorie restricted (CR) and control animals showed evidence for greater declines with age in relation to the other group, dependent on the region examined. CR animals showed attenuated age-related decline in several brain regions, including left superior longitudinal fasciculus, right inferior longitudinal fasciculus, right external capsule, left frontal short association fibers and left dorsal occipital bundle (shown in red below). Shown in blue are brain regions where the opposite was true, that is, CR showed a greater negative slope with age. These regions included portions of the thalamus and left inferior longitudinal fasciculus. The scatter plot on the right shows individual FA values from the left superior longitudinal fasciculus plotted against age. The control group (filled circles) shows a steeper slope with age compared to CR.