Geroprotective drug discovery with an AI-enabled assay for heat resistance

Abstract

Drugs that slow the rate of organismal aging (geroprotectors) have the potential to improve human healthspan by preventing the development of multiple chronic diseases. The nematode C. elegans is a proven system for identifying anti-aging drugs, but methods for candidate nomination that scale to high throughput remain limited and have not been widely adopted. To accelerate the discovery process, we have developed an open-source AI-enabled screening platform that provides a rapid, automated, posture-based score of C. elegans survival. We used this workflow to screen a library of 2,782 FDA-approved drugs and identified 31 compounds that reproducibly increase heat stress resistance, a known predictor of longevity. Follow-up studies confirmed that many of these compounds confer lifespan extension in worms, and several compounds also have anti-senescent activity in human cells. This simplified and adaptable AI-enabled workflow therefore has the potential to accelerate the discovery of translatable drugs that slow aging.