The field of aging research has grown rapidly over the last half-century, with advancement of scientific technologies to interrogate mechanisms underlying the benefit of life-extending interventions like calorie restriction (CR). Coincident with this increase in knowledge has been the rise of obesity and type 2 diabetes (T2D), both associated with increased morbidity and mortality. Given the difficulty in practicing long-term CR, a search for compounds (CR mimetics) which could recapitulate the health and longevity benefits without requiring food intake reductions was proposed. Alpha-glucosidase inhibitors (AGIs) are compounds that function predominantly within the gastrointestinal tract to inhibit α-glucosidase and α-amylase enzymatic digestion of complex carbohydrates, delaying and decreasing monosaccharide uptake from the gut in the treatment of T2D. Acarbose, an AGI, has been shown in pre-clinical models to increase lifespan (greater longevity benefits in males), with decreased body weight gain independent of calorie intake reduction. The CR mimetic benefits of acarbose are further supported by clinical findings beyond T2D including the risk for other age-related diseases (e.g., cancer, cardiovascular). Open questions remain regarding the exclusivity of acarbose relative to other AGIs, potential off-target effects, and combination with other therapies for healthy aging and longevity extension. Given the promising results in pre-clinical models (even in the absence of T2D), a unique mechanism of action and multiple age-related reduced disease risks that have been reported with acarbose, support for clinical trials with acarbose focusing on aging-related outcomes and incorporating biological sex, age at treatment initiation, and T2D-dependence within the design is warranted.

在过去的半个世纪里，随着科学技术的进步，人们对限制热量 (CR) 等延长生命的干预措施的益处背后的机制进行了探索，老龄化研究领域迅速发展。与知识的增长同时发生的是肥胖和 2 型糖尿病 (T2D) 的增加，两者都与发病率和死亡率的增加有关。鉴于实施长期 CR 的困难，有人提出寻找能够在不减少食物摄入量的情况下重述健康和长寿益处的化合物（CR 模拟物）。 α-葡萄糖苷酶抑制剂 (AGI) 是主要在胃肠道内发挥作用的化合物，可抑制 α-葡萄糖苷酶和 α-淀粉酶对复杂碳水化合物的酶促消化，从而延迟和减少肠道对单糖的摄取，从而治疗 T2D。阿卡波糖是一种 AGI，已在临床前模型中显示可以延长寿命（对男性有更大的长寿益处），并且体重增加减少，与卡路里摄入量的减少无关。阿卡波糖的 CR 模拟益处得到了 T2D 以外的临床发现的进一步支持，包括其他与年龄相关的疾病（例如癌症、心血管疾病）的风险。关于阿卡波糖相对于其他 AGI 的排他性、潜在的脱靶效应以及与其他疗法联合使用以实现健康衰老和延长寿命，仍然存在悬而未决的问题。 鉴于阿卡波糖在临床前模型中取得的有希望的结果（即使在没有 T2D 的情况下）、独特的作用机制以及已报道的阿卡波糖可降低多种与年龄相关的疾病风险，支持阿卡波糖关注衰老相关结果的临床试验将生物性别、开始治疗时的年龄和 T2D 依赖性纳入设计是有必要的。