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与健康和生活质量的改善密切相关。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，也是几种早发性遗传性结缔组织（CT）疾病的共同特征。由于细胞稳态的特定遗传干扰，这些疾病代表了这种与年龄相关的病理分子研究的独特工具。CHANGE的科学目标是：(i)研究CT疾病，以确定与年龄相关的生理功能下降有关的关键途径，意识到性别差异；（ii）更多地了解这些途径的相互依赖性，导致包括细胞衰老在内的刻板细胞反应。这一知识将为开发针对与衰老有关的常见疾病和虚弱的创新治疗策略铺平道路。为此，我们将培训和建立一个由10名具备科学专业知识、可转移技能和社会和环境意识的高技能早期研究人员组成的网络，为他们未来的职业生涯奠定基础。为了成功，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家公司（包括2家非学术合作伙伴）共同培养10名年轻科学家。ESR网络将通过深入研究CT疾病，揭示衰老的支柱及其多系统特征，从跨学科的角度解决衰老的基本生物学问题。总之，CHANGE将提供软骨、骨骼、肌肉和血管中与年龄相关的变化对早性疾病暴露的细胞/细胞外后果的综合图谱。

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.