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。虽然寿命更长会带来令人兴奋的机会，但衰老经常与健康状况不佳和脆弱有关。衰老的人口统计学使它的健康和社会护理负担大大增加，以及养老基金的财务挑战。在整个英国，在全球范围内，衰老的生活经验存在不平等，社会人口统计学，生活过程经验和遗传因素影响了不同人群的年代学和生物学年龄之间的严重差异。我们的应用集中在细胞外基质（ECM）的衰老（ECM）的衰老，组织和组织和organs和Organs的主要结构成分。 ECM是一个三维分子网络，不仅为体内的所有组织提供了弹性，还可以控制关​​键的生物物理信号以支持重要的细胞功能。 ECM占许多组织的很大一部分。例如，在骨骼中，ECM被矿化可提供必不可少的强度，而在肺部，它为正常功能提供了必要的弹性。每个器官中的ECM非常独特且非常动态，响应了各种外部因素，例如白天/夜间周期，突出了其锻造性。与年龄相关，ECM通过受生产和周转之间的不平衡，分子对分子的化学变化以及与我们的细胞的关系的影响而恶化。重要的是，ECM恶化随着年龄的直接影响我们体内细胞和组织的关键功能，导致细胞之间的异常沟通和重要功能的丧失，这有助于许多与年龄相关的疾病。在整个生命过程中，对ECM衰老构成了整个生命过程中的特定挑战，这是由于模型生物体和人类之间的差异而导致了使用人类的差异，而将人类的培养型越来越多。幸运的是，使用材料科学和组织工程中的方法来开发具有器官特异性ECM脚手架的人性化细胞模型具有巨大的潜力，可以实现高通量机理和药物筛查研究，以靶向与年龄相关的ECM降解以及对细胞衰老的作战标志，从而提供新颖的新颖，更有效和更安全的解决方案。我们提出了一个新的跨学科衰老网络，将生物学家，化学家，遗传学家，老化科学家，工程师，数学家，健康和社会科学家以及临床医生汇集在一起​​。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。我们将与行业利益相关者和技术提供商参与网络活动，并与公共和地方慈善机构联系，以与外部咨询小组的研究专家联系。该网络的重点将是增加对这个新的跨学科领域的了解，从而促进了快速发现和开创研究衰老的新模型的技术共享。我们的网络将为未来的研究提供知情的建议，以解决影响ECM老化的不平等现象。该网络将通过泵送活动，网络事件，网络活动以及将多样性和包容性纳入网络活动来提高现场的能力和多样性。该网络将通过促进会员注册和通信的网站接口运行。通讯将得到新闻通讯，社交媒体和网络活动的支持。更广泛地说，该网络将与相关的研究社会，相关网络，博士培训伙伴关系和技术人员开发中心进行交互。共享，共享模型，技术，知识和专业知识，我们独特的方法将产生范式变化的发现，并为发现科学和医学改善老年人的生命而带有长期益处。