The Baltimore Longitudinal Study Of Aging

巴尔的摩老龄化纵向研究(BLSA)是NIA目前关于人类老龄化的主要研究计划，自1958年以来一直在老年学研究中心进行，目前活跃在位于巴尔的摩海港医院的NIA-ASTRA(老龄翻译研究)单位。这项研究继续代表着一个科学家联盟，他们致力于描述正常和病理性衰老的特征。目前管理这项研究的研究团队正在对其设计和评估技术进行重大改变。主要的科学目标仍然是BLSA原始遗产中报告的那些目标：1)确定不能用疾病解释的个体之间与年龄相关的差异，以及2)表征影响从正常到病理性衰老转变的因素。然而，正在实施新的措施，目的是更好地了解年龄和疾病对导致许多老年人行动不便和生活质量低下的过程的影响。重点是综合和多学科的方法，以及在多个层面(细胞、组织、器官、全身、社会)自然实施的补偿机制，使许多老年人能够保持高水平的流动性，尽管有多种病理过程。 研究人群是一群志愿者，他们在多次随访中被终身跟踪。许多活跃的参与者已经在这项研究中工作了20多年，有些人甚至长达44年。未来，将实施一项筛查计划，以延长那些保持极高身体和认知功能水平的人的寿命。 在过去，BLSA一直是所有关于老龄化的流行病学研究的黄金标准参考。在心血管研究领域的重要发现，影响前列腺癌风险的因素，与年龄相关的认知功能下降，肌肉力量和骨骼力量，甚至在最近几年都有发表。将BLSA转移到ASTRA单位对于从临床角度实施一些新知识至关重要。为了实现这一目标，将同时进行BLSA的辅助研究，这些研究仅限于少数参与者，并涉及单一的预先制定的假设，更有可能提供可直接应用于临床医学的信息。 新BLSA设计的结构基于三个级别的措施： 1.参考的措施是身体和认知功能，所有其他措施，直接或间接旨在了解老年与发展为行动不便和认知功能受损的高风险有关的机制。因此，BLSA收集了一套关于身体和认知功能许多不同方面的广泛测量； 2.中间水平包括对活动很重要的生理系统的解剖完整性和功能的衡量：中枢神经系统、外周神经系统、肌肉、骨骼和关节、对产生能量重要的物质的输送、提供来自环境的反馈的感觉系统； 3.第三级包括对维持生物稳定很重要的生理系统，并包括免疫功能、激素、氧化应激/抗氧化剂、自主神经系统、营养摄入量和体力活动的措施。 这项研究的假设是，维持生物动态平衡的系统功能障碍是与年龄相关的身体功能下降和虚弱发展的主要原因。本质上，这一具体目标将由两个分项目来实现，这两个分项目在实际方面的设计略有不同，在科学范围内具有高度的相关性和互补性。 第一个分项目包括重新组织和记录BLSA在过去50年中收集的数据。该项目已处于开发的高级阶段，并已取得重要成果，涉及前列腺癌的临床特征与预后不良、白细胞的长期趋势及其与近半个世纪死亡率下降的关系，以及与身体功能加速下降有关的遗传特征。该计划的一个重要部分是对在整个研究过程中收集的生物标本(尿液、血液、血清、血浆、红细胞等)进行清点、分类和质量控制。此外，我们计划对大约1450名拥有可用DNA的参与者进行广泛的基因组扫描(Illumina 550K)。 第二个分项目包括招募一批特别健康的老年人(精英老龄化或非常成功的老年人)，研究这一群体与普通人群相比的横截面特征，并测量一些可能与身体和认知功能直接或间接相关的生理参数。从这个角度来看，BLSA的未来将成为一个永久的生理学实验室，研究衰老过程中发生的不同生理变化，最终目的是了解它们之间的相互关系，并描述它们有助于维持体内平衡的机制。

The Baltimore Longitudinal Study of Aging (BLSA), the Intramural NIA's current major research program on human aging, has been conducted at the Gerontology Research Center since 1958, and is now active at the NIA-ASTRA (Translational Research on Aging) Unit located at Harbor Hospital (Baltimore). The study continues to represent a consortium of scientists who work to characterize normal and pathological aging. The team of researchers currently managing the study is implementing major changes in its design and assessment technology. The primary scientific goals remain those that were reported in the original BLSA legacy: 1) to identify age-associated differences among individuals which are not explained by diseases, and 2) to characterize factors that affect the transitions from normal to pathological aging. However, new measures are being implemented that are aimed at gaining a better understanding of the effect of age and diseases on the process that leads to mobility disability and poor quality of life in many older adults. The focus is on an integrative and multidisciplinary approach, and the compensatory mechanisms that, naturally implemented at multiple levels (cells, tissues, organs, whole body, society) allow many older persons to maintain a high level of mobility, in spite of multiple pathological process. The study population is a cohort of volunteers that are followed for life over multiple follow-up visits. Many of the active participants have been in the study for more than 20 years, and some for as long as 44 years. In the future, a screening program will be implemented to longeve individuals that have maintained an extraordinary high level of physical and congnitive functioning. In the past, the BLSA has been the gold-standard reference for all epidemiological studies on aging. Important findings in the area of cardiovascular research, factors affecting the risk of prostate cancer, age-associated decline of cognitive function, muscle strength and bone strength were published even in recent years. Moving the BLSA to the ASTRA unit was vital to implementing some of the new knowledge in a clinical perspective. This goal will be pursued by conducting, in parallel, the BLSA ancillary studies that, being limited to a small number of participants and adressing a single, pre-formulated hypothesis, are more likely to provide information that can be directly applied in clinical medicine. The structure of the new BLSA design is based on three levels of measures: 1. The reference out come measures are physical and cognitive function and all other measures, directly or indirectly, are aimed at understanding the mechanisms by which old age is associated with high risk of developing mobility disability and impaired cognitive function. Accordingly, the BLSA collects an extensive set of measures of many difference aspects of physical and cognitive function; 2. The intermediate level includes measures of anatomical integrity and functionality of the physiological systems that are important for mobility: central nervous system, peripheral nervous system, muscle, bone and joints, delivery of substances important for energy production, sensory systems that provide feedback from the environment; 3. The third level includes the physiological systems that are important to maintain a stable biological homeostasis and include measures for immune function, hormones, oxidative stress/antioxidants, autonomic nervous system, nutritional intake, and physical activity. The hypothesis of the study is that a dysfunction of the systems that maintain the biological homeostasis is the primary cause of the age associated decline of physical function and of the development of frailty. In essence this specific aim will be pursued by two sub-projects, which are somewhat different in the design of practical aspects by highly related and complementary in the scientific scope. Thhe first sub-project consists in reorganizing and documenting the data collected by the BLSA over the last 5 decades. This project is already in an advanced stage of development and is already producing important results, concerning clinical feature for the diagnosis of prostate cancer associated with negative prognosis, secular trend of WBC and its relationship with the decline of mortality over the last half of the century, genetic traits that are associated with accelerated decline of physical function. An essential part of this plan is the inventory, classification and quality control of the entire collection of the biological specimens (urines, blood, serum, plasma, red blood cells etc) collected in BLSA participants during the entire course of the study. In addition, we plan to perfom a wide genome scan (Illumina 550K) in aroung 1450 participants who have available DNA. The second sub-project consists in recruiting a new cohort of exceptionally healthy older persons (Elite Aging or Extremely Successful Aging), look at the cross-sectional characteristics of this group compared to the general population, and measure a number of physiological parameters that may be directly or indirecly connected with physical and cognitive function. From this prospective, the future of the BLSA is to become a permanent laboratory of physiology that study the different physiological changes that occur over the aging process, with the final aim of understanding their inter-relationships and describing the mechanisms by which they contribute to the maintainance of the homeostatic equilibrium.