PHYSIOLOGIC & MOLECULAR BASIS OF THE SYNDROME OF FRAILTY

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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 we 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. As for our results, we have already begun to identify significant differences in immune 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. We have also detected higher IL6 in stimulated lymphocytes from frail as compared to non-frail subjects. This was in response to lipopolysacride (LPS) mitogen. These findings may help explain why frail older adults are at much higher risk of infection and sepsis than non-frail adults. The Exercise Core Lab was utilized for this protocol.