School of Medicine, Universidad de Los Andes, Bogotá, Colombia.
Endocrinology Section, Department of Internal Medicine, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
Adv Ther. 2020 Apr;37(4):1407-1424. doi: 10.1007/s12325-020-01287-0. Epub 2020 Mar 17.
Life expectancy has increased substantially over the last few decades, leading to a worldwide increase in the prevalence and burden of aging-associated diseases. Recent evidence has proven that cellular senescence contributes substantially to the development of these disorders. Cellular senescence is a state of cell cycle arrest with suppressed apoptosis and concomitant secretion of multiple bioactive factors (the senescence-associated secretory phenotype-SASP) that plays a physiological role in embryonic development and healing processes. However, DNA damage and oxidative stress that occur during aging cause the accumulation of senescent cells, which through their SASP bring about deleterious effects on multiple organ and systemic functions. Ablation of senescent cells through genetic or pharmacological means leads to improved life span and health span in animal models, and preliminary evidence suggests it may also have a positive impact on human health. Thus, strategies to reduce or eliminate the burden of senescent cells or their products have the potential to impact multiple clinical outcomes with a single intervention. In this review, we touch upon the basics of cell senescence and summarize the current state of development of therapies against cell senescence for human use.
在过去几十年中，预期寿命大大延长，导致与衰老相关的疾病在全球范围内的患病率和负担增加。最近的证据证明，细胞衰老对这些疾病的发展有很大的贡献。细胞衰老是一种细胞周期停滞的状态，伴有凋亡抑制和多种生物活性因子（衰老相关分泌表型-SASP）的共同分泌，它在胚胎发育和愈合过程中发挥着生理作用。然而，衰老过程中发生的 DNA 损伤和氧化应激导致衰老细胞的积累，这些细胞通过 SASP 对多个器官和系统功能产生有害影响。通过遗传或药理学手段消除衰老细胞会导致动物模型的寿命和健康寿命延长，初步证据表明它也可能对人类健康产生积极影响。因此，减少或消除衰老细胞或其产物负担的策略有可能通过单一干预措施对多种临床结果产生影响。在这篇综述中，我们探讨了细胞衰老的基础知识，并总结了目前针对人类使用的细胞衰老治疗方法的发展状况。
