Highlights of the October 2018 Journal Club: Unlocking Secrets of Drug Synergy to Slow Aging

Journal Club October 2018 – Drug Synergy Reduces Aging
The October Journal Club focuses on a study of worms in which a synergistic combination of compounds almost doubled their lifespan.

Summary There is an increasing interest in pharmacological intervention that directly targets the aging process. The pharmacological intervention against aging must be effective when initiated in adults, and ideally repurposed drugs. Drug combinations that target multiple evolutionarily conserved mechanisms and pathways of aging can lead to dramatic lifespan extensions. This approach was used in C.elegans to significantly prolong healthy lifespan and slow down aging. Transcriptomics and lipidomics analyses were used to identify the mechanisms of these drug synergies. We discovered that drug interactions were mediated by the TGF-b signaling pathway, which recruited genes involved in IGF signaling. Daf-2, daf-7 and sbp-1 interacted upstream of changes to lipid metabolism. This resulted in an increase in monounsaturated fat content, which is necessary for healthy lifespan extensions. These results suggest that combinations targeting different subsets of aging gene regulation network can lead to synergistic benefits in terms of lifespan.

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