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Geroprotective Effects of Drugs Modulating Metabolic Pathways: Perspectives of Pharmacology in Anti-Aging Therapy

Grycan M, Zyśk R, Grycan G, Jakiel G, Dudek A, Gromadzka G

International journal of molecular sciences, 2026

Abstract

Aging is the strongest risk factor for chronic diseases such as cardiovascular diseases, cancer, diabetes, and neurodegenerative disorders. Advances in geroscience indicate that pharmacological modulation of conserved molecular pathways may extend healthspan and delay multimorbidity. A structured narrative review of the PubMed, Scopus, and Web of Science literature published between January 2010 and May 2026 was conducted, with seminal earlier studies retained where relevant. The review focused on molecular pathways implicated in aging, pharmacological interventions targeting these pathways, and their preclinical and clinical evaluation. Particular emphasis was placed on translational evidence, including human biomarker studies and randomized clinical trials, and on the distinction between biomarker modulation and clinically meaningful outcomes. Repurposed drugs such as metformin and rapamycin have among the most extensive preclinical and translational evidence, although clinical evidence for broadly applicable geroprotection remains limited. Statins, SGLT2 inhibitors, GLP-1 receptor agonists, and menopausal hormone therapy have established disease-specific or cardiometabolic benefits that may have indirect relevance to geroprotection, but direct effects on biological aging and healthspan remain unproven. Other candidates, including senolytics, NAD+ precursors, taurine, and epigenetic reprogramming approaches, are at different stages of translational development, with…

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