a Buck Institute for Research on Aging , Novato , CA , USA.
b Drexel University College of Medicine , Philadelphia , PA , USA.
Expert Opin Drug Discov. 2019 Jun;14(6):541-548. doi: 10.1080/17460441.2019.1597049. Epub 2019 Apr 11.
Biology of aging is focused on elucidating the biochemical and genetic pathways that contribute to cellular damage accumulation over time. Thirty years of research are beginning to bear fruit as the first pharmacological interventions based on biology of aging go through clinical trials. Evolutionary theories of aging suggest that naturally selected traits believed to impart fitness in young organisms may be damaging in later life. Three major areas of focus in biology of aging are lifespan, healthspan, and rejuvenation. Areas covered: Aging research has produced several validated pharmacological interventions currently in clinical trials. Herein, the authors consider two representative case studies: 1) rapamycin analogs and their effect on the mTORC1 pathway, and 2) small molecules that target and kill senescent cells. The authors also provide their expert current and future perspectives on aging targeting drug discovery. Expert opinion: Aging-related therapeutic interventions will continue to emerge at an accelerating pace, both from research in biology of aging, as well as from coordinated biomedical research in aging-related chronic conditions.
衰老生物学的研究重点是阐明导致细胞损伤随时间积累的生化和遗传途径。三十年来的研究开始取得成果,第一批基于衰老生物学的药物干预措施正在进行临床试验。衰老的进化理论表明,在年轻生物体中被认为赋予适应性的自然选择特征,在晚年可能是有害的。衰老生物学的三个主要关注领域是寿命、健康寿命和恢复活力。涵盖领域:衰老研究已经产生了几种经过验证的药物干预措施,目前正在临床试验中。在此,作者考虑了两个代表性的案例研究:1)雷帕霉素类似物及其对 mTORC1 途径的影响,2)靶向并杀死衰老细胞的小分子。作者还提供了他们对衰老靶向药物发现的当前和未来的专家意见。专家意见:与衰老相关的治疗干预措施将继续以更快的速度出现,既来自衰老生物学的研究,也来自与衰老相关的慢性疾病的协调生物医学研究。