Reversing thymus involution by targeting long-lived stem cells

通过靶向长寿干细胞来逆转胸腺退化

• 批准号: EP/Y026543/1
• 负责人: Paola Bonfanti
• 金额: $ 16.19万
• 依托单位: The Francis Crick Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY026543%2F1
• 关键词: Reversing; thymus; involution; targeting; long

Ageing is accompanied by increased incidence of disorders that impair quality of life. It is a multifactorial process characterized by a progressive loss of tissue repairing capacity with increased inflammation, infections, and incidence of cancer, degenerative andchronic disorders. There is a need to target a societal major challenge which is represented by the dramatic increased of people aged over 60 years that will double by 2050 with enormous impact on health systems. Due to the intrinsic systemic nature of the immune system interconnecting all organs in our body, progressive immune senescence plays a major role in these age-associated disorders.The thymus is a primary lymphoid organ that provides immunity against pathogens, cancer and establishes long-term immune memory. Nevertheless, the thymus starts involuting with puberty and continue into adulthood with essentially atrophy in the elderly. Aged thymus has reduced capacity to raise response to vaccination and ability to eliminate self-reacting immune cells, contributing to inflammation, autoimmunity and cancer occurrence. Therefore, there is an urgent need to build a novel approach for development of therapeutics able to reverse thymus atrophy. Reversing thymus involution will increase circulating anti-inflammatory immune cells, process known as immune rejuvenation.The REVERSE THYME project has the main goal to develop a robust screening platform for identification of novel compounds able to activate long-lived, well characterized human epithelial stem cells to restore thymic stroma function and T cell output in aged or damaged thymus. The know-how developed in the host laboratory and our capacity to study thymic epithelial cells from aged and diseased thymi define our competitive advantage to develop a transformative approach to enhance the function of the thymus in several conditions affecting it throughout life and ageing.

老龄化伴随着损害生活质量的疾病发病率的增加。这是一个多因素的过程，其特征是组织修复能力的逐渐丧失，炎症、感染和癌症、退行性疾病和慢性疾病的发病率增加。有必要针对一个重大的社会挑战，其代表是60岁以上的人口急剧增加，到2050年将翻一番，对卫生系统产生巨大影响。由于免疫系统的内在系统性质将我们身体中的所有器官相互连接，进行性免疫衰老在这些与年龄相关的疾病中起着重要作用。胸腺是主要的淋巴器官，提供对病原体、癌症的免疫力，并建立长期免疫记忆。然而，胸腺在青春期开始退化，并持续到成年，老年人基本上萎缩。老化的胸腺降低了提高对疫苗接种的反应的能力和消除自我反应免疫细胞的能力，从而导致炎症、自身免疫和癌症的发生。因此，迫切需要建立一种新的方法来开发能够逆转胸腺萎缩的治疗方法。逆转胸腺退化将增加循环的抗炎免疫细胞，这一过程被称为免疫再生。REVERSE THYME项目的主要目标是开发一个强大的筛选平台，用于鉴定能够激活长寿命、特征良好的人类上皮干细胞的新型化合物，以恢复衰老或受损胸腺中的胸腺基质功能和T细胞输出。在主机实验室开发的专业知识和我们的能力，研究胸腺上皮细胞从老化和患病的胸腺定义我们的竞争优势，开发一种变革性的方法，以提高胸腺的功能，在几个条件影响它在整个生命和衰老。