Insilico Medicine Hong Kong Ltd., Hong Kong Science and Technology Park, New Territories, Hong Kong, China.
Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL 60637, USA.
Aging (Albany NY). 2022 Mar 29;14(6):2475-2506. doi: 10.18632/aging.203960.
Aging biology is a promising and burgeoning research area that can yield dual-purpose pathways and protein targets that may impact multiple diseases, while retarding or possibly even reversing age-associated processes. One widely used approach to classify a multiplicity of mechanisms driving the aging process is the hallmarks of aging. In addition to the classic nine hallmarks of aging, processes such as extracellular matrix stiffness, chronic inflammation and activation of retrotransposons are also often considered, given their strong association with aging. In this study, we used a variety of target identification and prioritization techniques offered by the AI-powered PandaOmics platform, to propose a list of promising novel aging-associated targets that may be used for drug discovery. We also propose a list of more classical targets that may be used for drug repurposing within each hallmark of aging. Most of the top targets generated by this comprehensive analysis play a role in inflammation and extracellular matrix stiffness, highlighting the relevance of these processes as therapeutic targets in aging and age-related diseases. Overall, our study reveals both high confidence and novel targets associated with multiple hallmarks of aging and demonstrates application of the PandaOmics platform to target discovery across multiple disease areas.
衰老生物学是一个有前途和新兴的研究领域,可以产生双重用途的途径和蛋白质靶点,可能影响多种疾病,同时延缓甚至可能逆转与年龄相关的过程。一种广泛用于分类驱动衰老过程的多种机制的方法是衰老的标志。除了经典的九大衰老标志外,还经常考虑诸如细胞外基质硬度、慢性炎症和逆转座子激活等过程,因为它们与衰老密切相关。在这项研究中,我们使用了 AI 驱动的 PandaOmics 平台提供的多种目标识别和优先级技术,提出了一系列有希望的新的与衰老相关的靶点,可用于药物发现。我们还在每个衰老标志中提出了一系列更经典的靶点,可用于药物重定位。通过这项全面分析生成的大多数顶级靶点都在炎症和细胞外基质硬度中发挥作用,突出了这些过程作为衰老和与年龄相关疾病治疗靶点的相关性。总的来说,我们的研究揭示了与多种衰老标志相关的高可信度和新靶点,并展示了 PandaOmics 平台在多个疾病领域的靶点发现中的应用。