Barbut Denise, Perni Michele, Zasloff Michael
BAZ Therapeutics, Inc., Philadelphia, PA, 19103, USA.
MedStar Georgetown Transplant Institute, Georgetown University School of Medicine, Washington, DC, 20010, USA.
NPJ Aging. 2024 Dec 19;10(1):62. doi: 10.1038/s41514-024-00188-8.
The development of anti-aging drugs is challenged by both the apparent complexity of the physiological mechanisms involved in aging and the likelihood that many of these mechanisms remain unknown. As a consequence, the development of anti-aging compounds based on the rational targeting of specific pathways has fallen short of the goal. To date, the most impressive compound is rapamycin, a natural bacterial product initially identified as an antifungal, and only subsequently discovered to have anti-aging properties. In this review, we focus on two aminosterols from the dogfish shark, Squalus acanthias, that we discovered initially as broad-spectrum anti-microbial agents. This review is the first to gather together published studies conducted both in vitro and in numerous vertebrate species to demonstrate that these compounds target aging pathways at the cellular level and provide benefits in multiple aging-associated conditions in relevant animal models and in humans. The dogfish aminosterols should be recognized as potential anti-aging drugs.
一是衰老过程涉及的生理机制明显复杂,二是许多此类机制可能仍不为人知。因此,基于合理靶向特定途径来开发抗衰老化合物的目标未能实现。迄今为止,最引人注目的化合物是雷帕霉素,它是一种天然细菌产物,最初被鉴定为抗真菌剂,后来才发现具有抗衰老特性。在这篇综述中,我们聚焦于白斑角鲨(Squalus acanthias)体内的两种氨基甾醇,它们最初是作为广谱抗菌剂被我们发现的。这篇综述首次汇集了在体外以及众多脊椎动物物种中开展的已发表研究,以证明这些化合物在细胞水平上靶向衰老途径,并在相关动物模型和人类的多种与衰老相关的病症中发挥有益作用。白斑角鲨氨基甾醇应被视为潜在的抗衰老药物。