A new compound that extends the lifespan of worms, with favorable in vitro properties and a lack of toxicity in rodents

Abstract

The development of geroprotectors, compounds that slow the biological aging process, is an important goal in modern medicine. These interventions hold the promise not only of extending lifespan, but more importantly, of extending healthspan-the period of life free from chronic disease. By targeting the fundamental mechanisms of aging, geroprotectors have the potential to simultaneously delay the onset and progression of multiple age-related conditions, thereby reducing the immense societal and economic burden of these illnesses. In this manuscript, we identified a new compound, MPOL_B_1, through a virtual screen targeting the proton-coupled folate transporter (PCFT). We describe the synthesis of MPOL_B_1 and two other lead compounds identified from the virtual screen. MPOL_B_1 had drug-like properties in vitro and a favorable safety profile in mice and rats. Most importantly, MPOL_B_1 increased the lifespan of the model organism C. elegans by up to 30%. Our findings suggest that MPOL_B_1 is a promising pro-longevity candidate that warrants further investigation, although its mechanism of action in animals requires additional studies.