Complexity Loss, Aging and the Dynamics of Frailty

此申请构成了过渡到K99独立途径的ROO阶段的请求 Awarid旨在促进和扩大基础和基础教育领域学术生涯的所有相互关联的组成部分， 人类衰老的应用方面。 博士IVladalena Costa的长期研究目标是：（i）了解非线性的基本机制 生物和生理控制的健康和他们的退化与老化和脆弱，（ii）开发一种新的 一类动态生物标志物，可量化整合功能并提供病理生理学信息 无法获得与传统的探测器，和（iii）以确定这种新的动态类的值 用于风险分层和评估旨在逆转或 延缓病理性衰老。 她的工作是在统计物理学，生物工程，生理学和衰老生物学的接口。两 这一跨学科工作的新兴主题是，健康的系统，其特点是鲁棒性 和适应性，表现出最复杂的多尺度动力学，而衰老和脆弱综合征， 特别是，其特征是复杂的多尺度变异性和适应能力的丧失。 博士科斯塔的K99奖使她成为一个独立的调查员在接口工作 复杂系统和生物衰老之间的联系 她在原提案中提出的ROO阶段的具体研究目标保持不变。 由基础K99培训和研究工作推动。科斯塔博士也在寻求一些 相互关联的子项目作为她的连贯计划的一部分，作为一个全职教师。具体目标 主要有：1）从发育动力学角度阐明综合生理控制的非线性机制 量化多尺度波动的生物标志物; 2）测试假设，即 生理调节机制在代表性系统中随着老化而退化， 3）检验生理系统复杂性随时间推移而丧失的假设， 预测整体健康状况恶化和随后的虚弱发展。

This application constitutes the request to transition to the ROO phase of a K99 Pathway to Indepentdence Awarid aimed at fostering and expanding ail the inter-related components of a academic career in basic and applied aspects of human aging. Dr. IVladalena Costa's long-term research goals are: (i) to understand basic mechanisms of nonlinear biologic and physiologic control in health and their degradation with aging and frailty, (ii) to develop a new class of dynamical biomarkers that quantify integrative function and give information about pathophysiology not obtainable with traditional probes, and (iii) to determine the value of this new class of dynamical biomarlcers for risk stratification and the assessment of therapeutic interventions designed to reverse or retard pathologic aging. Her work is at the interfaces of statistical physics, bioengineering, physiology, and the biology of aging. Two emerging themes of this interdisciplinary work are that healthy systems, which are marked by robustness and adaptability, exhibit the most complex multiscale dynamics, and that aging and the frailty syndrome in particular, are marked by a loss of complex multiscale variability and adaptive capacity. Dr. Costa's K99 award has allowed her to become an independent investigator working at the interface between complex systems and the biologic of aging. Her specific research aims for the ROO phase as presented in the original proposal remain unchanged. Propelled by the foundational K99 training and research work. Dr. Costa is also pursuing a number of inter-related sub-projects as part of her coherent program as a full time faculty member. The specific aims are: 1) to elucidate nonlinear mechanisms of integrative physiologic control by developing dynamical biomarkers that quantify multiscale fluctuations; 2) to test the hypothesis that the dynamical complexity of physiologic regulatory mechanisms degrades with aging in representative systems ranging from the cellular to organ, and 3) to test the hypothesis that loss of complexity in physiologic systems over time can be predictive of overall health status degradation and subsequent development of frailty.