细胞水平体外衰老模型的构建策略与研究进展

Strategies and research advances in constructing in vitro senescence models at the cellular level

摘要

随着科技进步,人类寿命延长,衰老相关问题备受关注.衰老作为现代医学面临的重大挑战,是由细胞衰老、基因组变异、端粒缩短、线粒体功能障碍等多因素驱动的复杂过程,与心血管疾病、癌症、阿尔茨海默病等多种老年疾病密切相关.其中,细胞衰老通过产生衰老相关分泌表型(senescence-associated secretory phenotype,SASP)破坏组织稳态,被视为衰老及年龄相关疾病的关键驱动因素.体外衰老模型的构建对揭示衰老机制及开发干预策略具有重要意义.根据诱导因素,衰老可分为4大核心类型:复制性衰老(replicative senescence,RS)、癌基因性衰老(oncogene-induced senescence,OIS)、应激诱导早衰(stress-induced premature senescence,SIPS)和治疗诱导衰老(treatment induced senescence,TIS).由于其关键机制尚不明确,且人类受试者研究受限(伦理、技术),建立可靠的衰老模型至关重要,而体外模型通过模拟细胞衰老过程,为剖析衰老机制、评估抗衰老疗法提供了可靠途径,有助于推动衰老相关疾病的干预研究.笔者聚焦多种体外衰老模型构建方法(辐射、药物作用、线粒体损伤、三维培养、器官芯片以及微生理系统和人工智能应用等),体现衰老的重要特征,以期为衰老研究提供新视角.

Abstract

With the advancement of technology and the extension of human lifespan,aging-related issues have attracted significant attention.As a major challenge in modern medicine,aging is a complex process driven by multiple factors such as cellular senescence,genomic variation,telomere shortening,mitochondrial dysfunction,etc.,and is closely associated with various age-related diseases including cardiovascular diseases,cancer,and Alzheimer's disease.Among these,cellular senescence disrupts tissue homeostasis by producing the senescence-associated secretory phenotype(SASP),and is regarded as a key driver of aging and age-related diseases.The construction of in vitro aging models is of great significance for revealing the mechanisms of aging and developing intervention strategies.According to the inducing factors,aging can be divided into four core types:replicative senescence(RS),oncogene-induced senescence(OIS),stress-induced premature senescence(SIPS),and treatment-induced senescence(TIS).Due to the unclear key mechanisms and the limitations of research on human subjects(ethical and technical constraints),establishing reliable aging models is crucial.In vitro models,by simulating the process of cellular sene-scence,provide a reliable approach for dissecting aging mechanisms and evaluating anti-aging therapies,thereby facilitating research into interventions for aging-related diseases.This review focuses on various methods for constructing in vitro senescence models(including radiation,drug action,mitochondrial damage,three-dimensional culture,organ-on-a-chip and microphysiological systems,and application of artificial intelligence,etc.),illustrating the critical features of senescence,with the aim of providing new perspectives for aging research.

关键词

衰老 / 体外 / 衰老模型

Key words

aging / in vitro / aging models

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基金资助

国家自然科学基金(82460763)

河北省自然科学基金(B2023205010)

广西科学院改革发展专项项目(2024YGFZ505-908)