Cellular Homeostasis ANd AGing in Connective TissuE Disorders

结缔组织疾病中的细胞稳态和衰老

• 批准号: EP/X031721/1
• 负责人: Tom Van Agtmael
• 金额: $ 33.8万
• 依托单位: University of Glasgow
• 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=EP%2FX031721%2F1
• 关键词: Cellular; Homeostasis; AGing; Connective; TissuE

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 elderly people, but also represent common traits in several early-onset hereditary connective tissue (CT) disorders. These disorders represent a unique tool for the molecular investigation of such age-related pathologies due to the specific genetic disturbance of cellular homeostasis. The scientific objectives of CHANGE are: (i) to investigate CT disorders to identify key pathways responsible for age-related decline of physiological functions, being aware of gender differences (ii) to learn more about the interdependency of these pathways leading to stereotypic cellular responses including cellular senescence.This knowledge will pave the way for developing innovative treatment strategies for common diseases and frailty associated with ageing. To this end, we will train and establish a network of 10 highly-skilled early stage researchers (ESRs) equipped with scientific expertise, transferable skills and societal and environment awareness as a foundation for their future careers. To succeed, CHANGE has built a unique and multidisciplinary network of 7 renowned academic partners and 5 companies (including 2 non-academics as associated partners) working together to train 10 young scientists. The ESR network will address the basic biology of ageing from an interdisciplinary perspective, by deeply investigating CT diseases to uncover the pillars of ageing and its multi-systemic signatures. Altogether, CHANGE will provide an integrative map of cellular/extracellular consequences of age-related changes in cartilage, bone, muscle and vasculature as consequences to precocious diseaseexposure.

发达国家寿命的延长不一定与健康和生活质量的改善齐头并进。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。这些疾病代表了一个独特的工具，这种年龄相关的病理学的分子研究，由于特定的遗传紊乱的细胞内稳态。变迁学会的科学目标是：（一）调查CT疾病，以确定与年龄相关的生理功能下降的主要途径，同时意识到性别差异;（二）更多地了解这些途径的相互依赖性，从而导致包括细胞衰老在内的定型细胞反应，这一知识将为制定与衰老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，这些研究人员拥有科学专业知识，可转移技能以及社会和环境意识，为他们未来的职业生涯奠定基础。为了取得成功，变迁学会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个非学术界的合作伙伴）组成，共同培训10名年轻科学家。ESR网络将从跨学科的角度解决衰老的基本生物学问题，通过深入调查CT疾病来揭示衰老的支柱及其多系统特征。总之，CHANGE将提供软骨、骨、肌肉和脉管系统中年龄相关变化的细胞/细胞外后果的综合地图，作为早熟疾病暴露的后果。