Department of Comparative Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Sci Rep. 2022 May 4;12(1):7300. doi: 10.1038/s41598-022-11229-1.
Pharmaceutical intervention of aging requires targeting multiple pathways, thus there is rationale to test combinations of drugs targeting different but overlapping processes. In order to determine if combining drugs shown to extend lifespan and healthy aging in mice would have greater impact than any individual drug, a cocktail diet containing 14 ppm rapamycin, 1000 ppm acarbose, and 1000 ppm phenylbutyrate was fed to 20-month-old C57BL/6 and HET3 4-way cross mice of both sexes for three months. Mice treated with the cocktail showed a sex and strain-dependent phenotype consistent with healthy aging including decreased body fat, improved cognition, increased strength and endurance, and decreased age-related pathology compared to mice treated with individual drugs or control. The severity of age-related lesions in heart, lungs, liver, and kidney was consistently decreased in mice treated with the cocktail compared to mice treated with individual drugs or control, suggesting an interactive advantage of the three drugs. This study shows that a combination of three drugs, each previously shown to enhance lifespan and health span in mice, is able to delay aging phenotypes in middle-aged mice more effectively than any individual drug in the cocktail over a 3-month treatment period.
衰老的药物干预需要针对多个途径，因此有理由测试针对不同但重叠过程的药物组合。为了确定将已证明可延长小鼠寿命和健康衰老的药物组合使用是否比任何单一药物更有效果，将含有 14 ppm 雷帕霉素、1000 ppm 阿卡波糖和 1000 ppm 苯丁酸钠的鸡尾酒饮食喂养给 20 月龄的 C57BL/6 和 HET3 四向杂交雌雄小鼠 3 个月。与单独用药物或对照处理的小鼠相比，用鸡尾酒处理的小鼠表现出与健康衰老一致的性别和品系依赖性表型，包括体脂减少、认知能力提高、力量和耐力增强以及与年龄相关的病理减少。与单独用药物或对照处理的小鼠相比，用鸡尾酒处理的小鼠的心脏、肺、肝和肾的年龄相关性病变严重程度持续降低，这表明这三种药物具有相互作用优势。这项研究表明，三种药物的组合，每种药物以前都被证明可以延长小鼠的寿命和健康寿命，能够比鸡尾酒中的任何单一药物更有效地延缓中年小鼠的衰老表型，在 3 个月的治疗期间。
