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

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 <i>in vitro</i> and a favorable safety profile in mice and rats. Most importantly, MPOL_B_1 increased the lifespan of the model organism <i>C. elegans</i> 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.

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Publication Details

Journal
RSC Medicinal Chemistry
Published
2025-12-09
DOI
https://doi.org/10.1039/d5md00780a
Primary Topic
Genetics, Aging, and Longevity in Model Organisms
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Michael Polymenis, Heidi M. Blank
RSC Medicinal Chemistry
Genetics, Aging, and Longevity in Model Organisms
article

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

Michael Polymenis, Heidi M. Blank
article en

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 <i>in vitro</i> and a favorable safety profile in mice and rats. Most importantly, MPOL_B_1 increased the lifespan of the model organism <i>C. elegans</i> 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.

RSC Medicinal ChemistryVol. 17(2)
Center for Advancing Health (US), Texas A&M University (US)
U.S. Department of Agriculture, National Institutes of Health, Agricultural Research Service
Openalex Percentile: Top 64%
Genetics, Aging, and Longevity in Model Organisms
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