Targeting of intracellular Ca 2+ stores as a therapeutic strategy against age-related neurotoxicities

J147 modulates Ca²⁺ metabolism in vivo

Rapidly aging SAMP8 mice recapitulate much of the progressive, age-associated decline in brain function that is associated with the development of AD in humans, developing both cognitive deficits and pathological hallmarks of dementia by 9 months of age¹³. Changes in hippocampal gene expression were examined between 9-month-old control mice and 13-month-old mice fed either control diet or J147 for 4 months starting at 9 months of age, a treatment that suppresses the aging phenotype¹². Because our screening platform is based in part upon calcium dysregulation, we used gene set enrichment analysis (GSEA) to ask how J147 affected age-associated changes corresponding to Ca²⁺-related ion channels and transporters.

There were significant, age-dependent differences in the expression of genes in these pathways that occurred between 9- and 13-months (Fig.