Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates- A Meta-Analysis

Ivimey-Cook, Edward R., Sultanova, Zahida and Maklakov, Alexei A. (2025) Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates- A Meta-Analysis. Aging Cell. ISSN 1474-9718 (In Press)

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Abstract

Dietary restriction (DR) robustly increases lifespan across taxa. However, in humans, long-term DR is difficult to maintain, leading to the search for compounds that regulate metabolism and increase lifespan without reducing caloric intake. The magnitude of lifespan extension from two such compounds, rapamycin and metformin, remains inconclusive, particularly in vertebrates. Here, we conducted a meta-analysis comparing lifespan extension conferred by rapamycin and metformin to DR-mediated lifespan extension across vertebrates. We assessed whether these effects were sex- and, when considering DR, treatment-specific. In total, we analysed 911 effect sizes from 167 papers covering eight different vertebrate species. We find that DR robustly extends lifespan across log-response means and medians and, importantly, rapamycin—but not metformin—produced a significant lifespan extension. We also observed no consistent effect of sex across all treatments and log-response measures. Furthermore, we found that the effect of DR was robust to differences in the type of DR methodology used. However, high heterogeneity and significant publication bias influenced results across all treatments. Additionally, results were sensitive to how lifespan was reported, although some consistent patterns still emerged. Overall, this study suggests that rapamycin and DR confer comparable lifespan extension across a broad range of vertebrates.

Item Type:	Article
Additional Information:	Publisher Copyright: © 2025 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
Uncontrolled Keywords:	dietary restriction,lifespan extension,meta-analysis,metformin,rapamycin,vertebrate,ageing,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1302
Faculty \ School:	Faculty of Science > School of Biological Sciences
Related URLs:	http://www.scopus.com/inward/record.url?... https://eprints.gla.ac.uk/352413/
Depositing User:	LivePure Connector
Date Deposited:	04 Sep 2025 13:30
Last Modified:	05 Sep 2025 08:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/100288
DOI:	10.1111/acel.70131

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