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Rapamycin, Not Metformin, Mirrors Dietary Restriction-Driven Lifespan Extension in Vertebrates: A Meta-Analysis
Edward R Ivimey-Cook1, Zahida Sultanova2, Alexei A Maklakov2
1School of Biodiversity, One Health, and Veterinary Medicine, University of Glasgow, Glasgow, UK.
Aging Cell
|June 18, 2025
Summary
Dietary restriction (DR) and rapamycin significantly extend lifespan in vertebrates. This meta-analysis found rapamycin
Area of Science:
- Gerontology and Longevity Research
- Comparative Biology and Evolution
- Pharmacology and Drug Discovery
Background:
- Dietary restriction (DR) is a well-established method for increasing lifespan across diverse species.
- Human adherence to long-term DR is challenging, prompting research into pharmacological interventions.
- Rapamycin and metformin are key compounds investigated for their potential to extend lifespan without caloric reduction.
Purpose of the Study:
- To conduct a meta-analysis comparing the lifespan-extending effects of rapamycin and metformin to those of DR across vertebrate species.
- To assess the influence of sex and treatment specificity on lifespan extension.
- To evaluate the robustness of DR effects across different methodologies and investigate potential publication bias.
Main Methods:
- A comprehensive meta-analysis was performed, incorporating 911 effect sizes from 167 published papers.
- The study included data from eight different vertebrate species to ensure broad applicability.
- Lifespan extension data for DR, rapamycin, and metformin were statistically analyzed, considering sex-specific effects and reporting variations.
Main Results:
- Dietary restriction (DR) robustly extended lifespan across log-response means and medians in vertebrates.
- Rapamycin demonstrated a significant lifespan-extending effect, whereas metformin did not show a consistent impact.
- No consistent sex-specific effects were observed across all treatments and lifespan measures, and DR effects remained robust despite methodological variations.
Conclusions:
- Rapamycin and DR confer comparable lifespan extension across a wide range of vertebrate species.
- The findings suggest rapamycin as a potential alternative for lifespan extension when DR is not feasible.
- Further research is warranted to address the heterogeneity and publication bias observed in the meta-analysis.
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