Targeting Ceramide Signaling: Enhancing Healthy Aging and Combating Tauopathy in Mammals

The study investigates the association between growth hormone deficiency and longevity in mouse models. We discovered that GHRH-KO mice with extended lifespans have different circulating lipid profiles, with ceramides being the most significantly altered lipid class. Ceramides have been implicated in several pathways related to aging, including insulin resistance, mitochondrial dysfunction, inflammation, apoptosis, and cellular senescence. The study aims to determine the role of ceramides in regulating healthspan and lifespan in mice, and to investigate the impact of genetic and pharmacological interventions that lower ceramide levels. The research approach involves integrating the understanding of GH action and ceramide signaling from the cellular and tissue levels to whole-animal outcomes. The results of this proposal will provide new insights into the differential mechanisms of action and offer the possibility of developing translational interventions. The proposed project is novel and has the potential to revolutionize our understanding of mammalian aging and longevity.