Walston Jeremy, Hadley Evan C, Ferrucci Luigi, Guralnik Jack M, Newman Anne B, Studenski Stephanie A, Ershler William B, Harris Tamara, Fried Linda P
Department of Medicine, Johns Hopkins Medical Institutions, 5505 Hopkins Bayview Circle, Baltimore, MD 21224, USA.
J Am Geriatr Soc. 2006 Jun;54(6):991-1001. doi: 10.1111/j.1532-5415.2006.00745.x.
Evolving definitions of frailty, and improved understanding of molecular and physiological declines in multiple systems that may increase vulnerability in frail, older adults has encouraged investigators from many disciplines to contribute to this emerging field of research. This article reports on the results of the 2004 American Geriatrics Society/National Institute on Aging conference on a Research Agenda on Frailty in Older Adults, which brought together a diverse group of clinical and basic scientists to encourage further investigation in this area. This conference was primarily focused on physical and physiological aspects of frailty. Although social and psychological aspects of frailty are critically important and merit future research, these topics were largely beyond the scope of this meeting. Included in this article are sections on the evolving conceptualization and definitions of frailty; physiological underpinnings of frailty, including the potential contributions of inflammatory, endocrine, skeletal muscle, and neurologic system changes; potential molecular and genetic contributors; proposed animal models; and integrative, system biology approaches that may help to facilitate future frailty research. In addition, several specific recommendations as to future directions were developed from suggestions put forth by participants, including recommendations on definition and phenotype development, methodological development to perform clinical studies of individual-system and multiple-system vulnerability to stressors, development of animal and cellular models, application of population-based studies to frailty research, and the development of large collaborative networks in which populations and resources can be shared. This meeting and subsequent article were not meant to be a comprehensive review of frailty research; instead, they were and are meant to provide a more-targeted research agenda-setting process.
衰弱的定义不断演变，人们对多个系统中可能增加衰弱老年人易损性的分子和生理衰退有了更深入的理解，这促使许多学科的研究人员投身于这个新兴的研究领域。本文报告了2004年美国老年医学会/国立衰老研究所关于老年人衰弱研究议程会议的结果，该会议汇聚了众多临床和基础科学家，以鼓励在这一领域开展进一步研究。本次会议主要聚焦于衰弱的身体和生理方面。尽管衰弱的社会和心理方面至关重要且值得未来研究，但这些主题在很大程度上超出了本次会议的范围。本文包括以下部分：衰弱概念的演变与定义；衰弱的生理基础，包括炎症、内分泌、骨骼肌和神经系统变化的潜在作用；潜在的分子和遗传因素；提议的动物模型；以及可能有助于推动未来衰弱研究的综合系统生物学方法。此外，根据参会者提出的建议制定了一些关于未来方向的具体建议，包括关于定义和表型发展的建议、开展个体系统和多系统对压力源易损性临床研究的方法学发展、动物和细胞模型的开发、基于人群的研究在衰弱研究中的应用，以及建立可共享人群和资源的大型协作网络。本次会议及后续文章并非对衰弱研究的全面综述；相反，它们旨在提供一个更具针对性的研究议程设定过程。
