Drug Cocktail Prevents Cognitive Decline in Aging Mice by Targeting Multiple Pathways

Our study focuses on addressing age-related cognitive decline by employing a novel pharmaceutical approach. Aging is a central risk factor for cognitive impairment, affecting various brain processes including nutrient sensing, insulin signaling, and histone deacetylation. To combat these effects, we developed a drug cocktail composed of rapamycin, acarbose, and phenylbutyrate, which have shown promise individually in previous studies.In our investigation, middle-aged mice were treated with this drug cocktail for three months, demonstrating enhanced resilience against age-related cognitive decline. To delve into the molecular mechanisms underlying this effect, we conducted comprehensive transcriptomic analysis using ribonucleic acid (RNA) sequencing. Gene set enrichment analysis revealed that the drug cocktail significantly influences aging-related pathways.Additionally, we validated these findings through immunohistochemistry, measuring molecular endpoints tied to aging pathways. The results exhibit a reduction in aging-related processes and a potential upregulation of autophagy in the brains of mice treated with the drug cocktail. Importantly, our analyses demonstrate that the combined cocktail treatment surpasses the individual drugs in mitigating cognitive impairment by targeting multiple aging pathways.In summary, our project uncovers the transformative potential of a multi-drug approach in alleviating age-related cognitive decline. The holistic impact of our drug cocktail, as evidenced by both transcriptomic and molecular analyses, underscores its promising for future therapeutic strategies.