Unitat de Bioquimica i Biotecnologia, Facultat de Medicina i Ciencies de la Salut, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
Biomedical Research Networking Center in Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
Curr Neuropharmacol. 2018;16(10):1466-1483. doi: 10.2174/1570159X15666170707155345.
An interesting area of scientific research is the development of potential antiaging drugs. In order to pursue this goal, it is necessary to gather the specific knowledge about the adequate preclinical models that are available to evaluate the beneficial effects of new potential drugs. This review is focused on invertebrate and vertebrate preclinical models used to evaluate the efficacy of antiaging compounds, with the objective to extend life span and health span.
Research and online content related to aging, antiaging drugs, experimental aging models is reviewed. Moreover, in this review, the main experimental preclinical models of organisms that have contributed to the research in the pharmacology of lifespan extension and the understanding of the aging process are discussed.
Dietary restriction (DR) constitutes a common experimental process to extend life span in all organisms. Besides, classical antiaging drugs such as resveratrol, rapamycin and metformin denominated as DR mimetics are also discussed. Likewise, the main therapeutic targets of these drugs include sirtuins, IGF-1, and mTOR, all of them being modulated by DR.
Advances in molecular biology have uncovered the potential molecular pathways involved in the aging process. Due to their characteristics, invertebrate models are mainly used for drug screening. The National Institute on Aging (NIA) developed the Interventions Testing Program (ITP). At the preclinical level, the ITP uses Heterogeneous mouse model (HET) which is probably the most suitable rodent model to study potential drugs against aging prevention. The accelerated-senescence mouse P8 is also a mammalian rodent model for aging research. However, when evaluating the effect of drugs on a preclinical level, the evaluation must be done in non-human primates since it is the mammalian specie closest to humans. Research is needed to investigate the impact of new potential drugs for the increase of human quality of life.
科学研究的一个有趣领域是开发潜在的抗衰老药物。为了追求这一目标，有必要收集有关现有适当临床前模型的具体知识，以评估新潜在药物的有益效果。本综述重点介绍了用于评估抗衰老化合物疗效的无脊椎动物和脊椎动物临床前模型，目的是延长寿命和健康寿命。
综述了与衰老、抗衰老药物、实验性衰老模型相关的研究和在线内容。此外，在本综述中，讨论了主要的实验性临床前模型的生物，这些模型为延长寿命的药理学研究和衰老过程的理解做出了贡献。
饮食限制（DR）是所有生物体延长寿命的常见实验过程。此外，还讨论了经典的抗衰老药物，如白藜芦醇、雷帕霉素和二甲双胍，它们被称为 DR 模拟物。同样，这些药物的主要治疗靶点包括 Sirtuins、IGF-1 和 mTOR，它们都受 DR 调节。
分子生物学的进步揭示了与衰老过程相关的潜在分子途径。由于其特点，无脊椎动物模型主要用于药物筛选。国家老龄化研究所（NIA）开发了干预测试计划（ITP）。在临床前水平，ITP 使用异质小鼠模型（HET），这可能是最适合研究潜在抗衰老药物的啮齿动物模型。加速衰老小鼠 P8 也是衰老研究的哺乳动物啮齿动物模型。然而，在临床前水平评估药物的效果时，必须在非人类灵长类动物中进行评估，因为它是最接近人类的哺乳动物物种。需要研究新的潜在药物对提高人类生活质量的影响。
