EcMagine': Extracellular Matrix ageing across the life course interdisciplinary research network

EcMagine：整个生命过程中的细胞外基质老化跨学科研究网络

• 批准号: BB/W018314/1
• 负责人: Elizabeth Laird
• 金额: $ 36.36万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW018314%2F1
• 关键词: EcMagine; Extracellular; Matrix; ageing; across

Advances in science, medicine and living conditions mean that people are living longer. Whilst a longer life brings exciting opportunities, ageing is too often associated with ill health and frailty. The ageing demographic brings with it a steep increase in the public burden of health and social care as well as financial challenges for pension funds. Across the UK, and globally, there are inequalities in the lived experience of ageing, with social demographics, life course experiences and genetic factors influencing stark disparities between chronological and biological age in different populations.Our application focusses on the ageing of extracellular matrix (ECM), the main structural component of tissues and organs. The ECM is a three-dimensional network of molecules which not only provides resilience to all tissues in the body, but also controls key biophysical signals to support vital cell functions. The ECM makes up a large fraction of many tissues; for example, in the bone, the ECM is mineralised providing essential strength, whilst in the lung, it provides elasticity necessary for normal function. The ECM in each organ is very distinct and very dynamic, responding to various external factors such as day/night cycles, highlighting its malleability.With age, ECM deteriorates through a process influenced by an imbalance between its production and turnover, chemical changes to molecules as well as changes in its relationship with our cells. Importantly, ECM deterioration with age directly influences key functions of cells and tissues in our body leading to abnormal communication between our cells and loss of vital functions, which contributes to many age-related diseases.Studying ECM ageing across the life course poses particular challenges due to differences between model organisms and humans, the limitations of using standard 2-dimensional culturing of isolated cells and difficulties in accessing healthy human tissues. Fortunately, using approaches in material science and tissue engineering to develop humanised cell models with organ-specific ECM scaffolds has enormous potential for high-throughput mechanistic and drug screening studies to target age-related ECM degradation and combat hallmarks of cellular ageing, thus offering novel, more effective and safer solutions. We propose a new interdisciplinary ageing network bringing together biologists, chemists, geneticists, ageing scientists, engineers, mathematicians, health and social scientists and clinicians. The network will be led by investigators at the Universities of Liverpool, Glasgow, Manchester, Nottingham and Newcastle but will operate across the whole of UK. We will engage industry stakeholders and technology providers in the network events and liaise with the public and local charities through to research experts on the external advisory panel. A key focus of the network will be increasing the knowledge of this new interdisciplinary field, facilitating sharing of technologies for rapid discoveries and pioneering new models to study ageing. Our network will provide informed recommendations for future research to address inequalities influencing ECM ageing.The network will act to increase capacity and diversity in the field through pump-priming activities, network events and incorporating diversity and inclusivity in network activities. The network will operate via a website interface facilitating member registration and communication. Communications will be supported by newsletters, social media and network events. More broadly, the network will interface with relevant research societies, related networks, doctoral training partnerships and technician development centres.Working together, sharing models, technologies, knowledge and expertise, our unique approach will generate paradigm-shifting discoveries with long-term benefits for discovery science, industry and medicine to improve lives of older people.

科学、医学和生活条件的进步意味着人们的寿命更长。虽然更长的寿命带来了令人兴奋的机会，但衰老往往与健康状况不佳和脆弱有关。人口老龄化使公共卫生和社会保健负担急剧增加，并给养恤基金带来财政挑战。在英国和全球范围内，老龄化的生活经验存在不平等，社会人口统计学，生命历程经验和遗传因素影响不同人群的实际年龄和生物年龄之间的明显差异。我们的应用程序集中在细胞外基质（ECM）的老化，组织和器官的主要结构成分。ECM是分子的三维网络，其不仅为身体中的所有组织提供弹性，而且还控制关键的生物物理信号以支持重要的细胞功能。ECM构成许多组织的大部分;例如，在骨中，ECM被矿化，提供必要的强度，而在肺中，它提供正常功能所需的弹性。每个器官中的ECM都是非常独特和动态的，对各种外部因素（如昼夜周期）做出反应，突出了其延展性。随着年龄的增长，ECM通过其生产和周转之间的不平衡，分子的化学变化以及与细胞关系的变化影响的过程而恶化。重要的是，ECM随着年龄的增长而退化，直接影响我们体内细胞和组织的关键功能，导致我们细胞之间的异常通讯和重要功能的丧失，这导致许多与年龄相关的疾病。由于模型生物和人类之间的差异，研究整个生命过程中的ECM老化带来了特殊的挑战，使用分离细胞的标准二维培养的局限性和获取健康人体组织的困难。幸运的是，利用材料科学和组织工程的方法开发具有器官特异性ECM支架的人源化细胞模型，对于高通量机制和药物筛选研究具有巨大的潜力，以靶向与年龄相关的ECM降解并对抗细胞衰老的标志，从而提供新颖，更有效和更安全的解决方案。我们建议建立一个新的跨学科老龄化网络，将生物学家、化学家、遗传学家、老龄科学家、工程师、数学家、卫生和社会科学家以及临床医生聚集在一起。该网络将由利物浦、格拉斯哥、曼彻斯特、诺丁汉和纽卡斯尔大学的调查人员领导，但将在整个英国运作。我们将让行业利益相关者和技术提供商参与网络活动，并通过外部咨询小组的研究专家与公众和当地慈善机构保持联系。该网络的一个主要重点将是增加对这一新的跨学科领域的了解，促进分享快速发现的技术，并开创研究老龄问题的新模式。我们的网络将为未来的研究提供明智的建议，以解决影响ECM老化的不平等问题。该网络将通过泵启动活动，网络活动以及将多样性和包容性纳入网络活动，提高该领域的能力和多样性。该网络将通过一个网站界面运行，方便成员注册和沟通。通讯、社交媒体和网络活动将为交流提供支持。更广泛地说，该网络将与相关研究协会、相关网络、博士培训伙伴关系和技术人员发展中心对接，共同努力，分享模式、技术、知识和专长，我们独特的方法将产生改变范式的发现，为发现科学、工业和医学带来长期利益，改善老年人的生活。