Novel Methodology for Identification of Senolytics that Reduce Age-related Disease and Dysfunction

描述（由申请人提供）：老年慢性疾病占医疗保健支出的很大比例，并导致数以千万计的美国人和全世界数亿人痛苦和有限的生存。Recursion制药公司开发了一个药物发现平台，可以将已知药物重新用于治疗此类疾病。该平台包括使用机器学习算法的高含量荧光图像分析，以识别在疾病和治疗建模的人类细胞中诱导的相关和靶向变化。该系统已被用于筛选可能优先破坏衰老细胞的药物，因为这可能导致组织功能的改善，并减少与衰老相关的病理和死亡率。在这个SBIR快速通道提案中，我们将：第一阶段确定各种人类细胞类型衰老的形态学特征。进展到第二阶段将取决于我们的能力，证明我们的形态学方法的力量，以识别衰老细胞独立于任何已知的衰老标志物。第二阶段：通过形态计量学方法鉴定出能够优先破坏衰老细胞而不影响健康细胞的已知药物。评估鉴定的抗衰老药物在多种小鼠组织功能和健康跨度模型中的功效。*评估已确定的抗衰老药物在小鼠年龄相关心血管疾病模型中的作用。Recursion Pharmaceuticals拥有经验、工具和动力来执行该I/ II期快速通道SBIR提案，并加速我们最终确定的任何化合物的商业开发。

DESCRIPTION (provided by applicant): Chronic diseases of aging account for a significant proportion of healthcare spending and result in a painful and limiting existence for many tens of millions of Americans and hundreds of millions of people around the world. Recursion Pharmaceuticals has developed a drug discovery platform that re-purposes known drugs for the treatment of such diseases. The platform consists of high content fluorescent image analysis using machine-learning algorithms to identify relevant and on-target changes induced in human cells in which diseases and treatments have been modeled. This system has been adapted to screen for drugs which may preferentially destroy senescent cells, as this may result in improved tissue function and decreases in pathology and mortality related to aging. In this SBIR fast-track proposal we will: PHASE I Identify a morphological profile of senescence in a variety of human cell types. Progression to Phase II will depend on our ability to demonstrate the power of our morphological approach to identify senescent cells independent of any known senescent markers. PHASE II Identify known drugs which preferentially destroy senescent cells, without affecting healthy cells, as identified by morphometric means. Evaluate the efficacy of identified senolytic agents in a variety of tissue function and health-span models in mice. *Evaluate the effect of identified senolytic agents in a murine model of age-associated cardiovascular disease. Recursion Pharmaceuticals has the experience, tools, and drive to execute this Phase I/Phase II Fast-track SBIR proposal, and to accelerate commercial development of any compounds we identify as a result.