CHANGE - Cellular Homeostasis And aGeing in Connective TissuE Disease (parent application EP/X031721/1)

发达国家寿命的延长并不一定伴随着健康和生活质量的改善。肌肉骨骼、心血管和神经退行性衰竭不仅是老年人身体和认知能力下降的标志，也是几种早期遗传性结缔组织(CT)疾病的共同特征。这些疾病代表了一种独特的工具，用于分子研究这种与年龄相关的病理，这是由于细胞内稳态的特定遗传障碍。改变的科学目标是：(I)调查CT障碍，以确定导致年龄相关性生理功能下降的关键途径，意识到性别差异(Ii)更多地了解导致刻板印象细胞反应(包括细胞衰老)的途径之间的相互依存关系。这些知识将为制定与老龄化相关的常见疾病和虚弱的创新治疗战略铺平道路。为此，我们将培训和建立一个由10名高技能早期研究人员(ESRS)组成的网络，这些研究人员配备了科学专业知识、可转让技能以及社会和环境意识，作为他们未来职业生涯的基础。为了取得成功，Change建立了一个独特的多学科网络，由7个著名的学术合作伙伴和5个公司(包括2个非学术合作伙伴)组成，共同培训10名年轻科学家。ESR网络将从跨学科的角度研究老龄化的基本生物学，深入研究CT疾病，以揭示老龄化的支柱及其多系统特征。总而言之，Change将提供一个综合地图，显示与年龄相关的软骨、骨骼、肌肉和血管变化的细胞/细胞外后果，以及早熟疾病暴露的后果。

The increased longevity in developed countries not necessarily goes hand in hand with amelioration of health and quality of life.Musculoskeletal, cardiovascular and neurodegenerative failure are not only hallmarks of the physical and cognitive decline in elderlypeople, but also represent common traits in several early-onset hereditary connective tissue (CT) disorders. These disorders representa unique tool for the molecular investigation of such age-related pathologies due to the specific genetic disturbance of cellularhomeostasis. The scientific objectives of CHANGE are: (i) to investigate CT disorders to identify key pathways responsible for agerelateddecline of physiological functions, being aware of gender differences (ii) to learn more about the interdependency of thesepathways leading to stereotypic cellular responses including cellular senescence. This knowledge will pave the way for developinginnovative treatment strategies for common diseases and frailty associated with ageing. To this end, we will train and establish anetwork of 10 highly-skilled early stage researchers (ESRs) equipped with scientific expertise, transferable skills and societal andenvironment awareness as a foundation for their future careers. To succeed, CHANGE has built a unique and multidisciplinarynetwork of 7 renowned academic partners and 5 companies (including 2 non-academics as associated partners) working together totrain 10 young scientists. The ESR network will address the basic biology of ageing from an interdisciplinary perspective, by deeplyinvestigating CT diseases to uncover the pillars of ageing and its multi-systemic signatures. Altogether, CHANGE will provide anintegrative map of cellular/extracellular consequences of age-related changes in cartilage, bone, muscle and vasculature asconsequences to precocious disease exposure.