Drug Synergy Slows Ageing and Improves Health Span through TGFF and SREBP Lipid Signaling

Abstract

Development of efficacious pharmacological interventions capable of modulating the ageing process would result in extension of human healthspan with dramatic medical and economic benefits. Such interventions would need to be efficacious even when started in adults and, ideally, repurpose existing drugs. Here we show that dramatic lifespan extension can be achieved by targeting multiple, evolutionarily conserved ageing pathways and mechanisms using drug combinations. Using this approach in C. elegans, we were able to slow ageing and significantly extend healthy lifespan. We find that daf-2, daf-7 and sbp-1 (mammalian SREBP-1c) interact upstream of changes in lipid metabolism, resulting in increased monounsaturated fatty acid content and extension of healthy lifespan. For one drug combination, we observed evolutionary conservation in fruit flies. To the best of our knowledge, this is the largest lifespan effect ever reported for any adult-onset drug treatment in C. elegans.