EXTENDING HEALTHY LIFESPAN BY SYSTEMATICALLY TARGETING AGEING PATHWAYS SYNERGIES

DIOGO GONCALVES BARARDO

Publication

EXTENDING HEALTHY LIFESPAN BY SYSTEMATICALLY TARGETING AGEING PATHWAYS SYNERGIES

DIOGO GONCALVES BARARDO

Abstract

Aging is the main risk factor underlying the dramatic increase in the incidence of cancer, cardiovascular, and neurodegenerative diseases in aging populations. Work on drugs and genes that affect lifespan in model organisms shows that the most significant lifespan effects result from pathway synergy and drug-drug interactions. Currently, it is unclear how common such synergistic interactions are or how best to leverage them therapeutically. I have created and validated an automated high-throughput screening platform for the identification of healthspan-extending drugs in Caenorhabditis elegans. Using this system, I conducted a large pilot screen for combinatorial drug benefits, identifying several new drug pairs with additive or synergistic benefits in terms of healthspan and lifespan. Furthermore, I generated and analyzed transcriptional signatures (RNA-Seq) for each drug. This information was then used to test the nature of drug synergies and explore approaches to predict beneficial drug-drug interactions based on transcriptional data from individual drugs.