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.

生物衰老涉及保守且可靶向的分子机制的相互作用，概括为衰老的标志。二甲双胍是一种双胍类药物，可对抗年龄相关疾病并改善健康寿命，是第一个在大型临床试验 TAME（二甲双胍靶向衰老）中测试其年龄靶向作用的药物。本综述重点关注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关联性的机制。这些特性使二甲双胍成为一种有吸引力的老年治疗药物，可以转化为人体试验。