l -去戊烯醇延长哺乳动物的寿命:22项长寿实验的荟萃分析

IF 12.4 1区 医学 Q1 CELL BIOLOGY
Michael R. Bene
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引用次数: 0

摘要

确定可重复延长寿命的干预措施是老年科学的中心目标,希望将这些发现转化为提高老年人的健康和寿命。l -去戊烯醇是一种FDA批准的药物,人们已经对其在衰老中的作用进行了30多年的研究。为了评估l -去戊烯醇对哺乳动物寿命的影响,我们对22个啮齿动物寿命实验进行了随机效应荟萃分析。结果表明,l -去戊烯醇显著提高平均寿命,效应大小中等(SMD = 0.6773, p = 0.0002)。我们在被检查的研究中没有发现明显的发表偏倚的证据,但确实观察到大量的异质性。对实验因素的考虑揭示了剂量(p = 0.0233)和起始年龄(p <; 0.0001)的显著影响,剂量越大,年龄越大,影响越大。通过对照者的平均寿命来评估治疗效果表明,短期对照不是观察到的效果的原因。除了meta分析,我们还重新分析了Ruehl等人的一项犬类生存研究。考虑到入组时的年龄和性别因素,该研究不再显示出对生存率的显著影响,尽管样本量小,影响有限。总之,这项对23项l -去戊烯醇寿命实验的分析跨越了27年的研究,涉及6个国家、8个啮齿动物品系、4个物种、6种剂量和2种给药方式,提供了一些最全面的数据,支持一种化合物对哺乳动物寿命的影响。未来的临床研究检查l -去戊烯醇对老年人健康结果的影响,对于确定这些发现的可转译性至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
L-deprenyl extends lifespan across mammalian species: A meta-analysis of 22 longevity experiments
Identifying interventions that reproducibly extend lifespan is a central aim in geroscience, with hopes of translating these findings to enhance the health and longevity of older adults. L-deprenyl, an FDA approved medication, has been investigated for its role in aging for over three decades. To evaluate the effect of L-deprenyl on lifespan in mammals we performed a random-effects meta-analysis on 22 rodent lifespan experiments. The results indicate L-deprenyl significantly increases average lifespan with moderate effect size (SMD = 0.6773, p = 0.0002). We identified no significant evidence of publication bias in the examined studies, but did observe substantial heterogeneity. Accounting for experimental factors revealed significant effects of dose (p = 0.0233) and age at initiation (p < 0.0001), with higher doses and older age associated with larger effects. Assessment of treatment effects by mean lifespan of controls suggests short-lived controls are not responsible for the observed effects. In addition to the meta-analysis, we reanalyzed a dog survival study by Ruehl et al. When accounting for age at enrollment and sex, the study no longer displayed a significant effect on survival, though power was limited by small sample size. Together, this analysis of 23 L-deprenyl lifespan experiments spans 27 years of research in 6 countries, 8 strains of rodents, 4 species, 6 doses, and 2 delivery methods, providing some of the most comprehensive data supporting the effect of a compound on lifespan in mammals. Future clinical studies examining L-deprenyls effects on health outcomes in older adults will be critical to determine the translatability of these findings.
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来源期刊
Ageing Research Reviews
Ageing Research Reviews 医学-老年医学
CiteScore
19.80
自引率
2.30%
发文量
216
审稿时长
55 days
期刊介绍: With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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