Max Planck Institute for Biology of Ageing, Department Biological Mechanisms of Ageing, Cologne, Germany.
Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, London, UK.
Nat Rev Drug Discov. 2020 Aug;19(8):513-532. doi: 10.1038/s41573-020-0067-7. Epub 2020 May 28.
Although death is inevitable, individuals have long sought to alter the course of the ageing process. Indeed, ageing has proved to be modifiable; by intervening in biological systems, such as nutrient sensing, cellular senescence, the systemic environment and the gut microbiome, phenotypes of ageing can be slowed sufficiently to mitigate age-related functional decline. These interventions can also delay the onset of many disabling, chronic diseases, including cancer, cardiovascular disease and neurodegeneration, in animal models. Here, we examine the most promising interventions to slow ageing and group them into two tiers based on the robustness of the preclinical, and some clinical, results, in which the top tier includes rapamycin, senolytics, metformin, acarbose, spermidine, NAD enhancers and lithium. We then focus on the potential of the interventions and the feasibility of conducting clinical trials with these agents, with the overall aim of maintaining health for longer before the end of life.
尽管死亡是不可避免的，但人们长期以来一直试图改变衰老过程的进程。事实上，衰老已经被证明是可以改变的；通过干预生物系统，如营养感应、细胞衰老、全身环境和肠道微生物组，可以减缓衰老表型的速度，足以减轻与年龄相关的功能下降。这些干预措施还可以延缓许多使人丧失能力的慢性疾病的发作，包括癌症、心血管疾病和神经退行性疾病，在动物模型中也是如此。在这里，我们检查了最有希望的减缓衰老的干预措施，并根据临床前结果的稳健性将它们分为两个层次，其中顶级层次包括雷帕霉素、衰老细胞清除剂、二甲双胍、阿卡波糖、亚精胺、NAD 增强剂和锂。然后，我们专注于这些干预措施的潜力以及用这些药物进行临床试验的可行性，总体目标是在生命结束前更长时间地保持健康。
