SFB 1506: Aging at Interfaces

与年龄有关的疾病共同导致与年龄有关的发病率和死亡率上升。尽管衰老与理解衰老有着重要的关系，但衰老如何从分子和细胞水平“传播”到影响整个器官和生物体仍然没有得到很好的理解。细胞和分子界面连接生物系统中的功能和结构单元。它们代表蛋白质、细胞、组织和器官之间的通信模块，在这些模块上启动决策并传递信息，突触或干细胞生态位界面就是此类界面的例子。因此，界面是多细胞生物的主要调控中心。失调的界面导致细胞和分子稳态的丧失。我们假设，衰老相关的组织腐烂以及衰老相关的疾病是在接口的相互作用的质量和数量的变化的结果。这些变化可能是：i）调节与其它蛋白质相互作用的蛋白质错误折叠，ii）一个受影响的细胞影响其周围细胞和/或iii）一个组织的老化表型被赋予另一个组织。深入了解界面的变化对于解码复杂生物体（如小鼠和人类）的潜在机制以及衰老的层次顺序至关重要。最重要的是，新的见解可能允许识别新的目标，用于开发治疗策略。CRC内的项目将侧重于脊椎动物模型系统，原代人类细胞/组织和健康老年受试者队列。衰老研究正朝着一个新的转变点发展：基于基础研究结果的抗衰老策略的发展。本CRC中产生的数据和知识将有助于这一转变。

Aging-related diseases which together contribute to age-associated elevated morbidity and mortality. Though of major and critical relevance for understanding aging, how aging “spreads” from the molecular and cellular level to affect whole organs and organisms is still not very well understood.Cellular and molecular interfaces connect functional and structural units in biological systems. They represent modules of communication between proteins, cells, tissues and organs, and at which decisions are initiated and information is passed on. Synapses or the stem-cell niche interface are examples of such interfaces. Interfaces are therefore primary regulatory hubs of multicellular organisms. Dysregulated interfaces contribute to the loss of cellular and molecular homeostasis. We hypothesize that aging-related tissue decay as well as aging-related diseases are a result of changes in both the quality and quantity of the interactions at interfaces. Such changes may be: i) protein misfolding that modulate interactions with other proteins, ii) one affected cell influencing its surrounding cells and/or iii) an aging phenotype of one tissue being conferred to another tissue. In depth knowledge on changes at interfaces will be critical to decode underlying mechanisms as well as the hierarchical order of aging in complex organisms such as mice and humans. Most importantly, novel insights might allow for the identification of novel targets for the development of therapeutic strategies. Projects within the CRC will focus on vertebrate model systems, primary human cells/tissues and a cohort of healthy elderly subjects. Aging research is in the process of moving towards a novel transition point for translation: the development of anti-aging strategies based on results from basic research. Data and knowledge generated in this CRC will contribute to this transition.