Administrative Core

摘要核心A 老年科学假说是基于这样一种观察，即健康寿命在生命结束时往往会下降， 出现单一的与年龄有关的疾病，随后是与年龄有关的并发症的快速积累 在相对较短的时间内。根据这一假设，治疗这些疾病中的任何一种， 治疗衰老的基本生物学只会导致它被另一种替代。虽然肺炎 导致老年人死亡率过高，大多数老年患者在获得现代医疗保健后存活 然而，在出院后的一年里，这些老年肺炎幸存者患肺炎的风险增加。 发生与年龄相关的疾病，包括持续性肺损伤、骨骼肌功能障碍， 不动、心肌梗塞、慢性肾病、痴呆和认知障碍。因此，在本发明中， 肺炎是一个网关的复合发病率，限制健康寿命在生命的尽头。在第一循环中 我们使用无偏见的转录组学和蛋白质组学方法来表明，与年龄相关的韧性可以 通过激活的整合应激反应，通过部分抑制线粒体代谢来恢复 转录因子4（ATF4）。核心A将协助PPG研究者检验这一中心假设， 通过一系列高度集成和创新的实验，专注于五个具体目标： 具体目标1。支持项目研究者、核心领导者、合作者之间的沟通 调查员以及内部和外部咨询委员会成员。 具体目标2。提供一个结构，以便在各机构之间分享材料和传播信息， 项目调查员、核心领导人及其合作者。 具体目标3。为项目和核心领导人提供财务和监管监督，并协调 他们与机构核心服务的互动。 具体目标4。通过出版物传播项目研究人员的发现， 向其他机构和其他研究者介绍和分享试剂和技术。 具体目标5.培养跨学科合作研究和指导的环境， 学生、博士后研究员和调查人员。

ABSTRACT CORE A The Geroscience hypothesis is based on the observation that healthspan decline toward the end of life often presents with a single age-related illness that is followed by the rapid accumulation of age-related complications over a relatively short period of time. According to this hypothesis, treating any one of these conditions without treating the fundamental biology of aging will only result in its substitution by another. Although pneumonia causes excess mortality in older people, most elderly patients with access to modern health care survive However, in the year after hospital discharge these older pneumonia survivors have an increased risk of developing age-related disorders including persistent lung injury, skeletal muscle dysfunction leading to immobility, myocardial infarction, chronic kidney disease, dementia and cognitive impairment. As such, pneumonia is a gateway for the compounding morbidity that limits healthspan at the end of life. In the first cycle of this award, we used unbiased transcriptomic and proteomic approaches to suggest age-related resilience can be restored by partial inhibition of mitochondrial metabolism through the integrated stress response via Activating Transcription Factor 4 (ATF4). Core A will assist the PPG investigators as they test this central hypothesis of this PPG through a highly integrated and innovative set of experiments by focusing on five Specific Aims: Specific Aim 1. To support communication between the Project Investigators, the Core Leaders, Collaborating investigators, and the Internal and External Advisory Committee members. Specific Aim 2. To provide a structure for the sharing of materials and dissemination of information between the Project Investigators, Core Leaders and their Collaborators. Specific Aim 3. To provide financial and regulatory oversight to the Project and Core Leaders and coordinate their interactions with Institutional Core Services. Specific Aim 4. To disseminate the discoveries made by the program project investigators through publications, presentations and the sharing of reagents and techniques to other institutions and other investigators. Specific Aim 5. To foster an environment of collaborative interdisciplinary research and mentoring of students, post-doctoral fellows and investigators.