PHYSIOLOGIC & MOLECULAR BASIS OF THE SYNDROME OF FRAILTY

生理

• 批准号: 7375796
• 负责人: Jeremy D Walston
• 金额: $ 1.52万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375796
• 关键词: PHYSIOLOGIC; MOLECULAR; BASIS; SYNDROME; FRAILTY

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Frailty is widely viewed by geriatricians as increasingly prevalent with old age. Elderly individuals who are frail are identified as a high risk subset of older adults who are most at risk for hospitalization, functional decline and early morbidity and mortality. The mechanisms by which frailty develop are unclear and may be related to underlying disease processes. However, it is likely that there are age related variations in physiologic parameters that are exaggerated in some individuals and which may influence the development of this syndrome. The specific aims are: 1) to characterize the association of a standardized defined phenotype of frailty with skeletal muscle mass and function as assessed by muscle power and strength; 2) to characterize the association between frailty and cortisol secretion, sex steroid levels, thyroid function, immune system function, and levels of cytokines; and 3) determine the relationship between physiologic and molecular parameters in the frail. To help identify underlying physiologic factors that may allow earlier interventions and head off the development of the syndrome of frailty, we will identify frail and non-frail individuals from a variety of sources throughout Johns Hopkins and surrounding centers. Ages >70 individuals will be screened excluding those with medical conditions that may cause abnormalities in the definition of frailty; such as Parkinson's disease, cerebral vascular accident with residual hemiparesis, symptomatic rheumatoid disease, symptomatic cardiovascular disease, and level of abnormality in the Folstein Mini Mental score. We will review medical charts for these and then perform the following exam on those who are not excluded secondary to medical diagnosis. Frailty is defined as having 3-5 components of a syndrome consisting of grip strength weakness, slow timed walking speed over 15 feet, subjective assessment of fatigue and low physical activity as well as unintentional weight loss of 5% or greater in the past 2 years. Using the same exam, we will identify a group of age-matched controls that meet none of the above criteria. The frail and non-frail participants will be enrolled in the second portion of the study at the GCRC. Anthropomorphic measurements will be performed after a nurse's exam, involving skin fold, biceps, triceps and inner thigh measurements using caliber and tape measurements. A DEXA scan will be performed on the GCRC unit in order to take meaurements of total lean body mass, total fat mass, and bone mineral density. Blood samples will be drawn on the unit as well as urine collection, which will be a 24-hour sample, returned to the unit the next day for analysis. We have identified significant differences in immune and endocrine system function between frail and non-frail cohorts. We have identified a lower lymphocyte proliferation rate in those frail individuals as compare to non-frail, and have now identified differential gene expression in monocytes from frail and non-frail participants. These findings may help explain why frail older adults are at much higher risk of infection and sepsis than non-frail adults, and will lead to other translational experiements involving immune system markers.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。老年病学家普遍认为，随着年龄的增长，虚弱越来越普遍。体弱的老年人被确定为老年人中的高风险亚群，他们最有可能住院治疗、功能衰退以及早期发病和死亡。虚弱发展的机制尚不清楚，可能与潜在的疾病过程有关。然而，可能存在生理参数的年龄相关变化，这些变化在某些个体中被夸大，并且可能影响该综合征的发展。具体目标是：1）表征虚弱的标准化定义表型与骨骼肌质量和功能（如通过肌肉力量和力量评估的）的关联; 2）表征虚弱与皮质醇分泌、性类固醇水平、甲状腺功能、免疫系统功能和细胞因子水平之间的关联;和3）确定虚弱者中生理和分子参数之间的关系。为了帮助确定潜在的生理因素，可能允许早期干预和阻止虚弱综合征的发展，我们将从约翰霍普金斯和周围中心的各种来源中确定虚弱和非虚弱的个体。年龄>70岁的个体将被筛选，排除那些具有可能导致虚弱定义异常的医学状况的个体;例如帕金森氏病、伴有残余轻偏瘫的脑血管意外、症状性类风湿性疾病、症状性心血管疾病和Folstein Mini Mental评分的异常水平。我们将审查这些病例的病历，然后对那些未因医学诊断而被排除的患者进行以下检查。虚弱被定义为具有3-5个综合征组成部分，包括握力虚弱、超过15英尺的缓慢计时步行速度、疲劳和低体力活动的主观评估以及过去2年内意外体重减轻5%或以上。使用相同的检查，我们将确定一组年龄匹配的对照，不符合上述标准。虚弱和非虚弱受试者将在GCRC入组研究的第二部分。在护士检查后进行拟人测量，包括皮褶、二头肌、三头肌和大腿内侧测量（使用口径和卷尺测量）。将在GCRC单元上进行DEXA扫描，以测量总瘦体重、总脂肪量和骨矿物质密度。将在单元上采集血液样本以及尿液样本，这将是一个24小时样本，第二天返回单元进行分析。 我们已经确定了虚弱和非虚弱队列之间的免疫和内分泌系统功能的显着差异。我们已经确定了较低的淋巴细胞增殖率在那些体弱的个人相比，非体弱，现在已经确定了差异基因表达的单核细胞从体弱和非体弱的参与者。这些发现可能有助于解释为什么虚弱的老年人比非虚弱的成年人感染和败血症的风险要高得多，并将导致涉及免疫系统标志物的其他翻译经验。