Repurposed FDA-approved drugs targeting genes influencing aging can extend lifespan and healthspan in rotifers

Area of Science:

• Gerontology and Pharmacology
• Drug discovery for aging interventions
• Biogerontology and translational aging research

Background:

• Pharmaceutical interventions offer controlled methods to slow aging, potentially complementing lifestyle changes like caloric restriction.
• FDA-approved drugs are a valuable resource for aging research due to established safety profiles.
• Off-target drug effects may present novel anti-aging benefits, necessitating systematic investigation.

Purpose of the Study:

• To identify existing FDA-approved drugs with potential anti-aging properties using computational screening.
• To validate candidate compounds through in vivo testing in a model organism for aging.
• To assess the impact of identified drugs on lifespan and healthspan in aging animals.

Main Methods:

• Computational drug screening using FINDSITE^comb to identify potential anti-aging targets among FDA-approved drugs.
• Multi-tiered in vivo screening of 31 candidate compounds using rotifers as a model for aging.
• Life table experiments and healthspan assessments (mitochondrial activity, mobility) to evaluate drug efficacy.

Main Results:

• Four drugs—erythromycin, carglumic acid, capecitabine, and ivermectin—significantly extended rotifer lifespan by 8-42% at low micromolar concentrations.
• Lifespan extension occurred without adverse effects on reproductive capacity.
• Positive impacts on healthspan markers, including mitochondrial activity and swimming speed, were observed.
• Significant lifespan extension (7-8.9%) was achieved even when drug treatment commenced in middle-aged rotifers.

Conclusions:

• Computationally guided screening of FDA-approved drugs can effectively identify novel anti-aging interventions.
• Erythromycin, carglumic acid, capecitabine, and ivermectin demonstrate potential for retarding aging and extending lifespan in model organisms.
• These findings support the exploration of existing pharmaceuticals for age-related healthspan and lifespan extension, even with late-stage intervention.