《生命科学》 2026, 38(6): 1058-1071

细胞衰老及衰老相关分泌表型

于振平¹ , 赖珩莉¹ , 向 阳^2,3 , 田小利^3,4,*

¹江西省人民医院及江西省心血管病医院，南昌 330006 ²南昌大学生命科学学院及人类衰老研究所代谢与肌少症研究室，南昌 330031 ³江西省衰老与疾病重点实验室，南昌 330031 ⁴南昌大学生命科学学 院及人类衰老研究所血管衰老及疾病研究室，南昌 330031

摘　要：

细胞衰老指细胞永久失去复制能力且具有以衰老相关分泌表型（senescence-associated secretory
phenotype，SASP）等为特征的生长状态，是个体衰老及疾病的危险因素。细胞衰老可分为主动型（程序型）和被动型（或诱导型）衰老。主动型衰老包括发育等过程中出现的衰老；被动型衰老包括复制型衰老、原癌基因诱导的衰老、组织损伤诱导的衰老、静息细胞起源型衰老，以及其他应激导致的衰老等。尽管衰老细胞不再分裂但仍保持代谢活性，可通过SASP因子发挥自分泌或旁分泌作用，参与多种生理和病理过程，包括细胞衰老状态维持、诱导周围细胞衰老、免疫监视与衰老细胞的清除、组织分化与形成、伤口愈合与组织纤维化控制、细胞干性调节等。虽然已知SASP组分主要包括促炎细胞因子、趋化因子、生长因子、胞外基质重塑酶、外泌体和其他活性成分，如活性脂质及代谢产物等，但事实上，SASP是一个动态过程，具有高度异质性，以适应复杂精细的细胞通讯需求。本文系统介绍细胞类型、衰老类型以及衰老程度等对SASP异质性的影响及机制，探讨通过控制SASP延缓或减轻衰老及相关疾病的可能性，以增加对细胞衰老异质性的认识。最后强调“延缓衰老”不仅是改善衰老标志物，而是通过维持、重建或改善细胞、组织以及个体的生理功能，达到老年健康的目标。

通讯作者：田小利 , Email:tianxiaoli@ncu.edu.cn

Cellular senescence and senescence-associated secretory phenotypes

YU Zhen-Ping¹ , LAI Heng-Li¹ , XIANG Yang^2,3 , TIAN Xiao-Li^3,4,*

¹Jiangxi Provincial Cardiovascular Hospital, Jiangxi Provincial People′s Hospital, Nanchang 330006, China ²Metabolic Control and Aging, Human Aging Research Institute and School of Life Science, Nanchang University, Nanchang 330031, China ³Jiangxi Key Laboratory of Aging and Diseases, Nanchang 330031, China ⁴Aging and Vascular Diseases, Human Aging Research Institute and School of Life Science, Nanchang University, Nanchang 330031, China

Abstract:

Cellular senescence refers to a permanent state of cell cycle arrest manifested primarily by the senescenceassociated secretory phenotype (SASP), acting as a key driver of organismal aging and agerelated diseases. It can be categorized into active senescence (or programmed senescence) and passive senescence that is induced by senescent stressors, including replication, oncogene, tissue damage, quiescence, and many others. SASP is a complex secretory mixture containing proinflammatory cytokines, chemokines, growth factors, extracellular matrix remodelers, damage-associated molecular patterns, and extracellular vesicles. Via autocrine and paracrine signaling, SASP exerts dual functions, that is, acute transient SASP mediates tumor suppression, wound healing, and development, whereas chronic persistent SASP promotes sustained inflammation, fibrosis, and disease progression. SASP is dynamic and regulated by multiple signaling pathways including ATM, p38 MAPK, cGAS-STING, which sense senescence stimuli such as DNA damage and oncogenic activation, and subsequently activate NFκB and C/EBPβ to drive SASP expression. SASP is highly heterogeneous, varying with senescence types, duration, and cell lineages. Senomorphic therapy targeting SASP mitigates tissue damage without eliminating senescent cells, offering advantages over senolytic approaches. Representative agents include rapamycin, metformin, resveratrol, and spermidine. Clinical translation faces challenges including inaccurate quantitative measurement of aging, SASP heterogeneity, undefined intervention windows, offtarget effects, and potential loss of beneficial SASP functions. Future strategies demand selective SASP inhibition to preserve beneficial signaling while suppressing detrimental components, with long-term efficacy validated by physiological functional assessments.

Communication Author：TIAN Xiao-Li , Email:tianxiaoli@ncu.edu.cn