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  1. James highlighted this interesting study [1] in his latest weekly CR research update (thanks James!). It focused on the impact in mice of CR on learning, memory, brain metabolism and brain structural integrity, all of which get messed up by 'normal' aging. Mice were started on CR at 14 weeks of age (quite young), and then tested when young or old, in comparison with AL fed mice using a battery of tests. I'm always skeptical of learning and memory tests in rodents, like the radial water maze test employed in this study, because it is hard to tease apart the effects of the better physical health of the CR animals relative to AL-fed controls, vs. better cognitive health in CR vs. AL animals. But FWIW, the old CR animals in this study did retain memory of the water maze solution better than old AL-fed controls, and comparable to young mice. The CR animals also seemed to shift from burning glucose in the brain to burning ketones, when the authors suggest is helpful for brain preservation. But I thought the most interesting part of the paper were the measurements performed to evaluate the impact of CR on the structure of the brain during aging, and in particular white matter integrity. They measured structural integrity of an important brain structure, the corpus callosum (CC) which connects the two hemispheres of the brain together, using state-of-the-art magnetic resonance diffusion tensor imaging (MR-DTI) - a technology widely employed in the human connectome project, but which I didn't realize could be applied to rodents. I can just imagine the little magnetic donuts they are sticking these mice in... Anyway, they found that the structural integrity of the CC (i.e. the connectivity between the two hemispheres) drops significantly (p < 0.0001) with age in the AL-fed mice. But it was almost entirely preserved in the old CR mice relative to either young AL or young CR mice. The graph on the right of this figure (Fig. 4 from the paper) shows this preservation: Figure 4: Caloric restriction preserved white matter structural integrity. (A) The region showing corpus callosum (CC) on MRI diffusion-weighted images. (B)The quantitative measurements of fractional anisotropy (FA) in CC. Data are presented as Mean ± SEM. ***p < 0.001 and ****p < 0.0001. So that is encouraging. Rather than turning our brains to mush, CR appears to preserve the integrity of important brain structures, at least in rodents and if started at an early age... --Dean ------------ [1] Front Aging Neurosci. 2015 Nov 13;7:213. Early Shifts of Brain Metabolism by Caloric Restriction Preserve White Matter Integrity and Long-Term Memory in Aging Mice. Guo J(1), Bakshi V(1), Lin AL(2). Free full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643125/ Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals' memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We found distinct patterns between normal aging and CR aging on brain functions - normal aging showed reductions in brain glucose metabolism, white matter integrity, and long-term memory, resembling human brain aging. CR aging, in contrast, displayed an early shift from glucose to ketone bodies metabolism, which was associated with preservations of brain energy production, white matter integrity, and long-term memory in aging mice. Among all the mice, we found a positive correlation between blood glucose level and body weight, but an inverse association between blood glucose level and lifespan. Our findings suggest that CR could slow down brain aging, in part due to the early shift of energy metabolism caused by lower caloric intake, and we were able to identify the age-dependent effects of CR non-invasively using neuroimaging. These results provide a rationale for CR-induced sustenance of brain health with extended longevity. PMCID: PMC4643125 PMID: 26617514
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