Institute for Aging Research, Albert Einstein College of Medicine, Bronx, New York, NY, USA; Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York, NY, USA.
Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Cell Metab. 2020 Jul 7;32(1):15-30. doi: 10.1016/j.cmet.2020.04.001. Epub 2020 Apr 24.
Biological aging involves an interplay of conserved and targetable molecular mechanisms, summarized as the hallmarks of aging. Metformin, a biguanide that combats age-related disorders and improves health span, is the first drug to be tested for its age-targeting effects in the large clinical trial-TAME (targeting aging by metformin). This review focuses on metformin's mechanisms in attenuating hallmarks of aging and their interconnectivity, by improving nutrient sensing, enhancing autophagy and intercellular communication, protecting against macromolecular damage, delaying stem cell aging, modulating mitochondrial function, regulating transcription, and lowering telomere attrition and senescence. These characteristics make metformin an attractive gerotherapeutic to translate to human trials.
生物衰老涉及保守和可靶向的分子机制的相互作用,这些机制被总结为衰老的特征。二甲双胍是一种用于治疗与年龄相关疾病并延长健康寿命的双胍类药物,它是第一种在大型临床试验-TAME(通过二甲双胍靶向衰老)中测试其针对衰老的靶向作用的药物。这篇综述重点介绍了二甲双胍通过改善营养感应、增强自噬和细胞间通讯、防止大分子损伤、延缓干细胞衰老、调节线粒体功能、调节转录以及降低端粒磨损和衰老来减轻衰老特征及其相互联系的机制。这些特征使二甲双胍成为一种有吸引力的 gerotherapeutic 药物,值得进行人体试验。