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

国际合作奖：利用人工智能评估钙化 VSMC 的衰老和线粒体形态

• 批准号: BB/Y513982/1
• 负责人: Vicky MacRae
• 金额: $ 32.86万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY513982%2F1
• 关键词: International; Partnering; Award; Using; AI

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.

在自然衰老过程中，钙化组织经常在动脉内形成，这些血管形成一个网络，将富含氧气的血液分配到整个身体。这个过程主要涉及动脉内主要细胞类型——血管平滑肌细胞（VSMC）的功能变化。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）的重要危险因素。识别参与动脉钙化的新分子和途径以及阻止这一过程的新药理学靶点可以降低心血管疾病的风险并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了钙化的 VSMC ，不仅会经历衰老​​（细胞老化、改变形状并永久停止分裂但不会死亡的过程），而且会表现出更长的线粒体（细胞的能量发源地），其工作效率较低（Phadwal 等）等，2023）。线粒体存在于几乎所有类型的细胞中，对于生存至关重要，因为它们产生细胞的能量。现在我们要问，我们的观察结果是否只是钙化的两个平行后果？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的了解将使我们的长期目标能够探索以衰老为目标的及时和创新的治疗策略，通过抑制动脉钙化来促进健康衰老。