International Partnering Award: Using AI to assess senescence and mitochondrial morphology in calcifying VSMCs

在自然衰老过程中，钙化组织经常在动脉内发展，动脉是形成将富氧血液分配到整个身体的网络的血管。这一过程主要涉及动脉内主要类型细胞（血管平滑肌细胞（VSMC））功能的变化。这是未来发生危及生命的心血管事件（包括心脏病发作和中风）的重要风险因素。识别与动脉钙化有关的新分子和途径，以及预防这一过程的新药理学靶点，可以降低心血管疾病的风险，提高老年人的生活质量。我们最近发表的开创性研究结果首次揭示，钙化的VSMCs不仅经历衰老，（细胞老化、改变形状和永久停止分裂但不死亡的过程），但也显示出较长的线粒体（细胞的能量发电站），其工作效率较低（Phadwal等人，2023年）。线粒体存在于几乎所有类型的细胞中，对生存至关重要，因为它们产生细胞的能量。我们现在要问，我们的观察结果是否只是钙化的两个平行结果？或者特定的VSMCS首先经历衰老，然后驱动这些细胞内的线粒体伸长？对这一过程的更全面理解将使我们能够长期探索衰老靶向作为一种及时和创新的治疗策略，通过抑制动脉钙化促进健康老龄化。

During natural ageing, calcified tissue frequently develops within arteries, the blood vessels that form a network to distribute oxygen-rich blood to the entire body. This process predominantly involves changes in the function of the main type of cell present within the arteries, the vascular smooth muscle cell (VSMC). This is a significant risk factor in the development of future life threatening cardiovascular events, including heart attack and stroke. Identifying new molecules and pathways involved in arterial calcification and novel pharmacological targets that prevent this process could reduce the risk of cardiovascular disease and enhance the quality of life for the elderly.We have recently published seminal findings revealing, for the first time, that calcifying VSMCs, not only undergo senescence (a process by which a cell ages, changes shape and permanently stops dividing but does not die), but also show longer mitochondria (the energy powerhouses of the cell) which work less efficiently (Phadwal et al., 2023). Present in nearly all types of cells, mitochondria are vital to survival as they generate the energy of the cell. We now ask are our observations simply two parallel consequences of calcification? Or do specific VSMCS first undergo senescence, which then drives mitochondrial elongation within those cells? A more complete understanding of this process will enable our long term ambition to explore the targeting of senescence as a timely and innovative treatment strategy to promote healthy ageing through the inhibition of arterial calcification.