全球范围内普遍存在的人口老龄化趋势将对全球的健康和社会系统带来挑战。这一现象是由于医疗进步使寿命延长所致，预计美国有20%的人口很快将年满65岁。因此，老年疾病将呈现激增趋势。衰老表现为分子和细胞水平上生物维持和稳态丧失的物理状态，与或直接导致年龄相关的表型变化有关。免疫系统的衰退是衰老过程中的一个关键因素，癌症是老年人群主要的死因之一。嵌合抗原受体（CAR）T细胞疗法是一种创新方法，在儿童和青年成人血液恶性肿瘤中已经取得了成功，但在影响老年人群的疾病（如晚年B细胞恶性肿瘤和大多数实体肿瘤症状）中仍然效果不佳。这种限制产生的原因在于CAR T细胞的功效在很大程度上依赖于患者衍生的起始T细胞材料的质量。大量研究表明，T细胞衰老可能是CAR T细胞缺陷的主要驱动因素。本综述探讨了与有利CAR T细胞结果相关的相关因素和基本因素，并探索了T细胞复juvenation的潜在实验和临床可行策略。版权所有 © 2023 Elsevier Ltd. 保留所有权利。

Population aging, a pervasive global demographic trend, is anticipated to challenge health and social systems worldwide. This phenomenon is due to medical advancements enabling longer lifespans, with 20% of the US population soon to be over 65 years old. Consequently, there will be a surge in age-related diseases. Senescence, characterized by the loss of biological maintenance and homeostasis at molecular and cellular levels, either correlates with or directly causes age-related phenotypic changes. Decline of the immune system is a critical factor in the senescence process, with cancer being a primary cause of death in elderly populations. Chimeric antigen receptor (CAR) T cell therapy, an innovative approach, has demonstrated success mainly in pediatric and young adult hematological malignancies but remains largely ineffective for diseases affecting older populations, such as late-in-life B cell malignancies and most solid tumor indications. This limitation arises because CAR T cell efficacy heavily relies on the fitness of the patient-derived starting T cell material. Numerous studies suggest that T cell senescence may be a key driver of CAR T cell deficiency. This review examines correlates and underlying factors associated with favorable CAR T cell outcomes and explores potential experimental and clinically actionable strategies for T cell rejuvenation.Copyright © 2023 Elsevier Ltd. All rights reserved.