CR Way Protects Against Dementia

canstockphoto7434360The Brain Booster teleconference on Saturday began with a celebration song: Welcome to my World by Jim Reeves.

Welcome to my world 
Won’t you come on in?
Miracles, I guess,
Still happen now and then.

Setting the seeds for the celebration was the brilliant discovery by scientists at Columbia University who found that increasing the RbAp48 gene in the dentate gyrus restores the memories of old mice to perform like those of much younger animals. The dentate gyrus is a part of the hippocampus that is important for memory function.

Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48

Pavlopoulos E, Jones S, Kosmidis S, Close M, Kim C, Kovalerchik O, Small SA, Kandel ER.

Science Translational Medicine. 2013 Aug 28;5(200):200ra115. doi: 10.1126/scitranslmed.3006373. PMID: 23986399


To distinguish age-related memory loss more explicitly from Alzheimer’s disease (AD), we have explored its molecular underpinning in the dentate gyrus (DG), a subregion of the hippocampal formation thought to be targeted by aging. We carried out a gene expression study in human postmortem tissue harvested from both DG and entorhinal cortex (EC), a neighboring subregion unaffected by aging and known to be the site of onset of AD.

(Using expression in the EC for normalization,) we identified 17 genes that manifested reliable age-related changes in the DG. The most significant change was an age-related decline in RbAp48, a histone-binding protein that modifies histone acetylation. To test whether the RbAp48 decline could be responsible for age-related memory loss, we turned to mice and found that, consistent with humans, RbAp48 was less abundant in the DG of old than in young mice. We next generated a transgenic mouse that expressed a dominant-negative inhibitor of RbAp48 in the adult forebrain.

  • Inhibition of RbAp48 in young mice caused hippocampus-dependent memory deficits similar to those associated with aging, as measured by novel object recognition and Morris water maze tests. Functional magnetic resonance imaging studies showed that within the hippocampal formation, dysfunction was selectively observed in the DG, and this corresponded to a regionally selective decrease in histone acetylation.
  • Up-regulation of RbAp48 in the DG of aged wild-type mice ameliorated age-related hippocampus-based memory loss and age-related abnormalities in histone acetylation.

Together, these findings show that the DG is a hippocampal subregion targeted by aging, and identify molecular mechanisms of cognitive aging that could serve as valid targets for therapeutic intervention.

  Copyright © 2013, American Association for the Advancement of Science

Earlier research from Columbia has shown that poor glucose control causes deterioration of the dentate gyrus and development of senile dementia.

So why the celebration music at the Brain Booster teleconference? Because the CR Way approach to low GI calorie restriction is likely to maintain RbAp48, helping members protect against dementia.

Welcome to the LivingTheCRWay World!

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