Senescent cells accumulate throughout the body with advanced age, diseases and chronic conditions. They negatively impact health and function of multiple systems, including the central nervous system (CNS). Therapies that target senescent cells, broadly referred to as senotherapeutics, recently emerged as potentially important treatment strategies for the CNS. Promising therapeutic approaches involve clearing senescent cells by disarming their pro-survival pathways with ‘senolytics’; or dampening their toxic senescence-associated secretory phenotype (SASP) using ‘senomorphics’. Following the pioneering discovery of first-generation senolytics dasatinib and quercetin, dozens of additional therapies have been identified, and several promising targets are under investigation. Although potentially transformative, senotherapies are still in early stages and require thorough testing to ensure reliable target engagement, specificity, safety and efficacy. The limited brain penetrance and potential toxic side effects of CNS-acting senotherapeutics pose challenges for drug development and translation to the clinic. This Review assesses the potential impact of senotherapeutics for neurological conditions by summarizing preclinical evidence, innovative methods for target and biomarker identification, academic and industry drug development pipelines and progress in clinical trials.

衰老细胞随着高龄、疾病和慢性病而积聚到全身。它们会对多个系统的健康和功能产生负面影响，包括中枢神经系统 （CNS）。针对衰老细胞的疗法，通常称为 senotherapeutics，最近成为 CNS 的潜在重要治疗策略。有前途的治疗方法包括通过用“senolytics”解除其促生存途径来清除衰老细胞;或使用“同形学”抑制其毒性衰老相关分泌表型 （SASP）。继开创性地发现第一代 senolytics dasatinib 和 quercetin之后，已经确定了数十种其他疗法，并且正在研究几个有前途的靶点。尽管具有潜在的变革性，但 senotherapy 仍处于早期阶段，需要进行全面测试，以确保可靠的靶点参与、特异性、安全性和有效性。CNS 作用性 senotherapeutics 有限的脑外显率和潜在的毒副作用对药物开发和临床转化构成了挑战。本综述通过总结临床前证据、靶点和生物标志物识别的创新方法、学术和行业药物开发管道以及临床试验的进展，评估了 senotherapeutics 对神经系统疾病的潜在影响。