Canagliflozin Reprograms the Aging Hippocampus in Genetically Diverse UM-HET3 Mice and Attenuates Alzheimer's-Like Pathology.

ABSTRACT: Aging is the strongest risk factor for cognitive decline and Alzheimer's disease (AD), yet the mechanisms underlying brain aging and their modulation by pharmacological interventions remain poorly defined. The hippocampus, essential for learning and memory, is particularly vulnerable to metabolic stress and inflammation. Canagliflozin (Cana), an FDA-approved sodium-glucose co-transporter 2 inhibitor (SGLT2i) for type 2 diabetes, extends lifespan in male but not female mice, but its impact on brain aging is unknown. Here, we used a multi-omics strategy integrating transcriptomics, proteomics, and metabolomics to investigate how chronic Cana treatment reprograms brain aging in genetically diverse UM-HET3 mice. In males, Cana induced mitochondrial function, insulin and cGMP-PKG signaling, and

SUBMITTER: Jayarathne H 

PROVIDER: S-EPMC12686575 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature