Omics approaches for discovery of natural anti‐aging and anti‐cancer compounds and defining mechanisms of their action

• DOI: 10.1096/fasebj.30.1_supplement.831.4
• Publication Date: 2023-11-26T16:48:44Z
• Authors: Vladimir Titorenko; Anna Leonov; Anthony Arlia‐Ciommo; Younes Medkour; Veronika Svistkova
• Keywords: Calorie Restriction; Nutrient Sensing

Caloric restriction (CR) and dietary (DR) extend lifespan across species improve health by delaying the onset of age‐related diseases. All currently known anti‐aging chemical compounds (1) mimic lifespan‐extending health‐improving effects CR DR without restricting caloric nutrient intake; (2) target signaling pathways that are under stringent control calorie and/or availability. It was believed therefore all longevity “adaptable” nature because they modulate only in response to certain changes extracellular intracellular energy status an organism. However, it is possible some could be “constitutive” or “housekeeping” irrespective We designed a high‐throughput genetic screen for increase yeast modulating such housekeeping pathways. Our identified lithocholic acid (LCA) as one them. Using proteomics, lipidomics, metabolomics cell biological approaches, we found LCA delays aging by: remodeling lipid metabolism endoplasmic reticulum, droplets peroxisomes ‐ thereby preventing liponecrotic programmed death caused accumulation fatty acids; repertoire mitochondrial membrane lipids reducing number mitochondria, increasing their size, expanding cristae, elevating abundance respiratory supercomplexes inner membrane, altering dynamics respiration, potential reactive oxygen species; (3) attenuating fragmentation suppressing mitochondria‐controlled apoptosis; (4) promoting “mitohormesis” through activation several stress response‐related processes mitochondria. findings also imply that, addition its robust effect, exhibits potent selective anti‐tumor effect cultured human neuroblastoma, glioma, breast cancer prostate cells activating both intrinsic extrinsic apoptotic death. Support Funding Information Supported NSERC Canada.