Repurposing FDA-approved drugs for anti-aging therapies

Area of Science:

• Gerontology
• Drug Discovery
• Computational Biology

Background:

• Aging is a complex process involving multiple pathways.
• Repurposing FDA-approved drugs offers a safe and efficient strategy for anti-aging therapies.
• Existing drugs have known mechanisms and safety profiles, reducing development time and cost.

Purpose of the Study:

• To identify FDA-approved drugs with anti-aging potential by screening against aging-related protein targets.
• To experimentally validate the effects of identified drug candidates on lifespan and healthspan in a model organism.
• To explore computational methods combined with experimental validation for rapid anti-aging drug discovery.

Main Methods:

• Utilized FINDSITE^comb, a ligand homology modeling program, to identify potential binding partners for aging-related proteins.
• Screened a library of DrugBank drugs, including 1347 FDA-approved molecules, against targets from transient receptor potential gene 7, ribosomal protein S6 polypeptide 2, and forkhead box C.
• Tested top-ranked drugs for lifespan and healthspan extension in the rotifer *Brachionus manjavacas* model, assessing mobility, reproduction, and mitochondrial activity.

Main Results:

• Naproxen (1 µM) significantly extended mean rotifer lifespan by 14%.
• Naproxen, fludarabine, and hydralazine improved age-related decline in swimming speed (mobility).
• Naproxen, fludarabine, and hydralazine enhanced reproduction and preserved mitochondrial activity in aging rotifers.

Conclusions:

• Combining computational drug screening with experimental validation is an effective approach for identifying anti-aging drug candidates.
• The rotifer *Brachionus manjavacas* serves as a valuable model for initial screening of anti-aging compounds.
• Identified drugs demonstrate potential for both lifespan extension and healthspan improvement, warranting further investigation in vertebrate models.