Department of Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China.
Department of Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China; Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou 510632, China.
Pharmacol Ther. 2020 Dec;216:107673. doi: 10.1016/j.pharmthera.2020.107673. Epub 2020 Sep 11.
Aging is a natural biological progress accompanied by the gradual decline in physiological functions, manifested by its close association with an increased incidence of human diseases and higher vulnerability to death. Those diseases include neurological disorders, cardiovascular diseases, diabetes, and cancer, many of which are currently without effective cures. Even though aging is inevitable, there are still interventions that can be developed to prevent/delay the onset and progression of those aging-associated diseases and extend healthspan and/or lifespan. Here, we review decades of research that reveals the molecular pathways underlying aging and forms the biochemical basis for anti-aging drug development. Importantly, due to the vast chemical space of natural products and the rich history of herb medicines in treating human diseases documented in different cultures, natural products have played essential roles in aging research. Using several of the most promising natural products and their derivatives as examples, we discuss how natural products serve as an inspiration resource that helped the identification of key components/pathways underlying aging, their mechanisms of action inside the cell, and the functional scaffolds or targeting mechanisms that can be learned from natural products for drug engineering and optimization. We argue that natural products might eventually provide a solution to aging and aging-associated diseases.
衰老是一种自然的生物进程,伴随着生理功能的逐渐下降,其与人类疾病发病率的增加和更高的死亡率密切相关。这些疾病包括神经紊乱、心血管疾病、糖尿病和癌症,其中许多目前尚无有效治疗方法。尽管衰老是不可避免的,但仍可以开发干预措施来预防/延缓与衰老相关的疾病的发生和进展,并延长健康寿命和/或寿命。在这里,我们回顾了几十年来的研究,这些研究揭示了衰老的分子途径,并为抗衰老药物的开发提供了生化基础。重要的是,由于天然产物的化学空间广阔,以及不同文化中记载的草药治疗人类疾病的丰富历史,天然产物在衰老研究中发挥了重要作用。我们使用几种最有前途的天然产物及其衍生物作为例子,讨论了天然产物如何作为灵感资源,帮助确定衰老的关键成分/途径、它们在细胞内的作用机制,以及可以从天然产物中学到的功能支架或靶向机制,用于药物工程和优化。我们认为,天然产物最终可能为衰老和衰老相关疾病提供解决方案。