From the RNA-Mediated Mechanisms of Disease group, College of Medicine and Health, Institute of Biomedical and Clinical Science, University of Exeter.
Plast Reconstr Surg. 2021 Jan 1;147(1S-2):25S-32S. doi: 10.1097/PRS.0000000000007618.
Cellular senescence is a state of stable cell cycle arrest that has increasingly been linked with cellular, tissue, and organismal aging; targeted removal of senescent cells brings healthspan and lifespan benefits in animal models. Newly emerging approaches to specifically ablate or rejuvenate senescent cells are now the subject of intense study to explore their utility to provide novel treatments for the aesthetic signs and diseases of aging in humans. Here, we discuss different strategies that are being trialed in vitro, and more recently in vivo, for the targeted removal or reversal of senescent cells. Finally, we describe the evidence for a newly emerging molecular mechanism that may underpin senescence; dysregulation of alternative splicing. We will explore the potential of restoring splicing regulation as a novel "senotherapeutic" approach and discuss strategies by which this could be integrated into the established portfolio of skin aging therapeutics.
细胞衰老是一种稳定的细胞周期停滞状态，越来越多地与细胞、组织和机体衰老相关联；有针对性地清除衰老细胞可在动物模型中带来健康寿命和寿命的益处。目前，新出现的专门清除或使衰老细胞年轻化的方法正成为深入研究的课题，以探索它们在为人类衰老的美容标志和疾病提供新的治疗方法方面的应用。在这里，我们讨论了不同的策略，这些策略正在体外和最近在体内进行试验，以有针对性地清除或逆转衰老细胞。最后，我们描述了一个新兴的分子机制的证据，该机制可能是衰老的基础；可变剪接的失调。我们将探讨将剪接调节恢复作为一种新的“衰老治疗”方法的潜力，并讨论将其整合到现有的皮肤衰老治疗药物组合中的策略。
