Benhamú Bellinda, Martín-Fontecha Mar, Vázquez-Villa Henar, López-Rodríguez María L, Ortega-Gutiérrez Silvia
Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Departamento de Química Orgánica, Facultad de Óptica y Optometría, Universidad Complutense de Madrid, 28037 Madrid, Spain.
Biomedicines. 2022 Aug 18;10(8):2006. doi: 10.3390/biomedicines10082006.
Aging is considered the main risk factor for many chronic diseases that frequently appear at advanced ages. However, the inevitability of this process is being questioned by recent research that suggests that senescent cells have specific features that differentiate them from younger cells and that removal of these cells ameliorates senescent phenotype and associated diseases. This opens the door to the design of tailored therapeutic interventions aimed at reducing and delaying the impact of senescence in life, that is, extending healthspan and treating aging as another chronic disease. Although these ideas are still far from reaching the bedside, it is conceivable that they will revolutionize the way we understand aging in the next decades. In this review, we analyze the main and well-validated cellular pathways and targets related to senescence as well as their implication in aging-associated diseases. In addition, the most relevant small molecules with senotherapeutic potential, with a special emphasis on their mechanism of action, ongoing clinical trials, and potential limitations, are discussed. Finally, a brief overview of alternative strategies that go beyond the small molecule field, together with our perspectives for the future of the field, is provided.
衰老被认为是许多常见于老年的慢性疾病的主要风险因素。然而，这一过程的必然性正受到近期研究的质疑，该研究表明衰老细胞具有使其与年轻细胞区分开来的特定特征，并且清除这些细胞可改善衰老表型及相关疾病。这为旨在减少和延缓衰老对生命影响的针对性治疗干预措施的设计打开了大门，即延长健康寿命并将衰老视为另一种慢性疾病来治疗。尽管这些想法距离应用于临床仍很遥远，但可以想象它们将在未来几十年彻底改变我们对衰老的理解方式。在本综述中，我们分析了与衰老相关的主要且经过充分验证的细胞途径和靶点，以及它们在衰老相关疾病中的作用。此外，还讨论了具有衰老治疗潜力的最相关小分子，特别强调了它们的作用机制、正在进行的临床试验以及潜在局限性。最后，简要概述了超越小分子领域的替代策略，以及我们对该领域未来的展望。
