Qin Tian, Chen Tao, Ma Rui, Li Huan, Li Cui, Zhao Jin, Yuan Jinguo, Zhang Zuoming, Ning Xiaoxuan
Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an, China.
Aging Dis. 2024 Jul 16;16(4):1946-1970. doi: 10.14336/AD.2024.0262.
Cellular senescence is a complex process involving multiple factors, such as genetics, environment, and behavior. However, recent studies have shown that stress also plays a crucial role in inducing cellular senescence. Stress can affect cellular function and structure through various pathways, leading to accelerated aging. Exposure to stressful conditions can alter the neuroendocrine system, activate the hypothalamus-pituitary-adrenal axis and sympathetic adrenal medullary axis, and release cortisol and catecholamines, causing mitochondrial dysfunction, generating excessive reactive oxygen species, and inducing oxidative stress, DNA damage, and inflammatory reactions, ultimately resulting in accelerated cellular senescence. The process of stress-induced cellular senescence has been implicated in a number of chronic diseases, including age-related macular degeneration, chronic kidney disease, type 2 diabetes, cardiovascular disease and obstructive sleep apnea. In this review, we integrate recent progress research progress in our understanding of the mechanisms of stress-induced cellular senescence and discuss its underlying mechanisms from the perspective of stress hormones. We review potential therapeutic targets for stress-induced premature senescence and discuss the advantages and limitations of existing pharmacological agents capable of ameliorating stress-induced premature senescence.
细胞衰老 是一个涉及多种因素的复杂过程,如遗传、环境和行为。然而,最近的研究表明,应激在诱导细胞衰老中也起着关键作用。应激可通过多种途径影响细胞功能和结构,导致加速衰老。暴露于应激条件下会改变神经内分泌系统,激活下丘脑-垂体-肾上腺轴和交感肾上腺髓质轴,并释放皮质醇和儿茶酚胺,导致线粒体功能障碍,产生过多的活性氧,并诱导氧化应激、DNA损伤和炎症反应,最终导致细胞衰老加速。应激诱导的细胞衰老过程与许多慢性疾病有关,包括年龄相关性黄斑变性、慢性肾病、2型糖尿病、心血管疾病和阻塞性睡眠呼吸暂停。在这篇综述中,我们整合了我们对应激诱导细胞衰老机制理解的最新研究进展,并从应激激素的角度讨论其潜在机制。我们综述了应激诱导过早衰老的潜在治疗靶点,并讨论了现有能够改善应激诱导过早衰老的药物的优缺点。