Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Consejo Superior de Investigaciones Científicas, 41013 Seville, Spain.
CIBERONC, Instituto de Salud Carlos III, 28029 Madrid, Spain.
Cells. 2022 Apr 4;11(7):1222. doi: 10.3390/cells11071222.
Cellular senescence is a stress-response mechanism that contributes to homeostasis maintenance, playing a beneficial role during embryogenesis and in normal adult organisms. In contrast, chronic senescence activation may be responsible for other events such as age-related disorders, HIV and cancer development. Cellular senescence activation can be triggered by different insults. Regardless of the inducer, there are several phenotypes generally shared among senescent cells: cell division arrest, an aberrant shape, increased size, high granularity because of increased numbers of lysosomes and vacuoles, apoptosis resistance, defective metabolism and some chromatin alterations. Senescent cells constitute an important area for research due to their contributions to the pathogenesis of different diseases such as frailty, sarcopenia and aging-related diseases, including cancer and HIV infection, which show an accelerated aging. Hence, a new pharmacological category of treatments called senotherapeutics is under development. This group includes senolytic drugs that selectively attack senescent cells and senostatic drugs that suppress SASP factor delivery, inhibiting senescent cell development. These new drugs can have positive therapeutic effects on aging-related disorders and act in cancer as antitumor drugs, avoiding the undesired effects of senescent cells such as those from SASP. Here, we review senotherapeutics and how they might affect cancer and HIV disease, two very different aging-related diseases, and review some compounds acting as senolytics in clinical trials.
细胞衰老是一种应激反应机制，有助于维持内稳态，在胚胎发生和正常成年生物体中发挥有益作用。相比之下，慢性衰老激活可能是导致与年龄相关的疾病、HIV 和癌症发展等其他事件的原因。细胞衰老的激活可以由不同的刺激引发。无论诱导物如何，衰老细胞通常都具有几种共同的表型：细胞分裂停滞、形态异常、体积增大、由于溶酶体和空泡数量增加而导致的颗粒度增加、抗凋亡、代谢缺陷和一些染色质改变。衰老细胞因其对不同疾病（如虚弱、肌肉减少症和与衰老相关的疾病，包括癌症和 HIV 感染）发病机制的贡献而成为研究的一个重要领域，这些疾病表现出加速衰老。因此，正在开发一种称为衰老治疗学的新的药理学治疗类别。该组包括选择性攻击衰老细胞的衰老细胞溶解药物和抑制 SASP 因子传递的衰老细胞静止药物，抑制衰老细胞的发展。这些新药可能对与衰老相关的疾病具有积极的治疗作用，并在癌症中作为抗肿瘤药物发挥作用，避免衰老细胞的不良影响，如 SASP。在这里，我们回顾衰老治疗学以及它们如何影响两种非常不同的与衰老相关的疾病——癌症和 HIV 疾病，并回顾一些在临床试验中作为衰老细胞溶解剂的化合物。
