Ivimey-Cook Edward R, Sultanova Zahida, Maklakov Alexei A
School of Biodiversity, One Health, and Veterinary Medicine, University of Glasgow, Glasgow, UK.
School of Biological Sciences, University of East Anglia, Norwich, UK.
Aging Cell. 2025 Sep;24(9):e70131. doi: 10.1111/acel.70131. Epub 2025 Jun 18.
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.
饮食限制（DR）能显著延长各类生物的寿命。然而，对人类而言，长期坚持饮食限制很难做到，因此人们开始寻找在不减少热量摄入的情况下调节新陈代谢并延长寿命的化合物。雷帕霉素和二甲双胍这两种化合物对寿命延长的程度尚无定论，在脊椎动物中尤其如此。在此，我们进行了一项荟萃分析，比较了雷帕霉素和二甲双胍与饮食限制介导的寿命延长在脊椎动物中的效果。我们评估了这些影响是否具有性别特异性，以及在考虑饮食限制时是否具有治疗特异性。我们总共分析了来自167篇论文的911个效应量，这些论文涵盖了8种不同的脊椎动物物种。我们发现，饮食限制在对数反应均值和中位数上都能显著延长寿命，重要的是，雷帕霉素能显著延长寿命，而二甲双胍则不能。我们还观察到，在所有治疗方法和对数反应测量中，性别没有一致的影响。此外，我们发现饮食限制的效果不受所用饮食限制方法类型差异的影响。然而，高异质性和显著的发表偏倚影响了所有治疗方法的结果。此外，结果对寿命的报告方式很敏感，尽管仍出现了一些一致的模式。总体而言，这项研究表明，雷帕霉素和饮食限制在广泛的脊椎动物中能带来相当的寿命延长。
