Moskalev Alexey, Chernyagina Elizaveta, Kudryavtseva Anna, Shaposhnikov Mikhail
1Laboratory of postgenomic studies, Engelhardt Institute of Molecular Biology of Russian Academy of Sciences, Moscow, 119991, Russia.
2Laboratory of genetics of aging and longevity, Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia.
Aging Dis. 2017 May 2;8(3):354-363. doi: 10.14336/AD.2016.1022. eCollection 2017 May.
Although the geroprotectors discovery is a new biomedicine trend and more than 200 compounds can slow aging and increase the lifespan of the model organism, there are still no geroprotectors on the market. The reasons may be partly related to the lack of a unified concept of geroprotector, accepted by the scientific community. Such concept as a system of criteria for geroprotector identification and classification can form a basis for an analytical model of anti-aging drugs, help to consolidate the efforts of various research initiatives in this area and compare their results. Here, we review the existing classification and characteristics of geroprotectors based on their effect on the survival of a group of individuals or pharmaceutics classes, according to the proposed mechanism of their geroprotective action or theories of aging. After discussing advantages and disadvantages of these approaches, we offer a new concept based on the maintenance of homeostatic capacity because aging can be considered as exponential shrinkage of homeostatic capacity leading to the onset of age-related diseases and death. Besides, we review the most promising current screening approaches to finding new geroprotectors. Establishing the classification of existing geroprotectors based on physiology and current understanding of the nature of aging is essential for putting the existing knowledge into a single system. This system could be useful to formulate standards for finding and creating new geroprotectors. Standardization, in turn, would allow easier comparison and combination of experimental data obtained by different research groups.
尽管发现老年保护剂是一种新的生物医学趋势,并且有200多种化合物可以延缓衰老并延长模式生物的寿命,但市场上仍然没有老年保护剂。原因可能部分与科学界尚未接受统一的老年保护剂概念有关。作为老年保护剂识别和分类标准体系的这一概念,可以构成抗衰老药物分析模型的基础,有助于整合该领域各种研究计划的努力并比较其结果。在此,我们根据老年保护剂对一组个体生存的影响或药物类别、其提出的老年保护作用机制或衰老理论,综述了老年保护剂的现有分类和特点。在讨论了这些方法的优缺点之后,我们提出了一个基于维持稳态能力的新概念,因为衰老可以被视为稳态能力的指数性下降,导致与年龄相关疾病的发生和死亡。此外,我们还综述了当前寻找新老年保护剂最有前景的筛选方法。基于生理学和当前对衰老本质的理解来建立现有老年保护剂的分类,对于将现有知识整合到一个单一体系中至关重要。这个体系可能有助于制定寻找和创造新老年保护剂的标准。反过来,标准化将使不同研究小组获得的实验数据更容易进行比较和整合。