Age-related inflammatory changes: The role of genes and body composition changes

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DESCRIPTION (provided by applicant): This proposal aims to quantify the effects of inflammatory genes and body composition changes on age-related changes in inflammatory markers. Inflammation has been implicated in a number of diseases and conditions that affect older adults including atherosclerotic cardiovascular disease (ASCVD). Inflammatory activity increases with aging, however, the knowledge about the natural history of this change and its origins and consequences is extremely limited. We postulate that age-related changes in inflammatory markers are partially explained by age-related changes in adiposity and inflammatory gene polymorphisms, and may be an important risk factor for subsequent ASCVD. Longitudinal data analyses using the Health Aging and Body Composition (Health ABC) Study, a prospective study of 3,075 black and white, men and women in their seventies who have been followed annually since 1997-98, will allow us to efficiently achieve the following specific aims: 1) to determine the pattern of changes in inflammatory markers with age during 7 years of follow-up; 2) to test the extent to which observed changes in inflammatory markers can be attributed to increase in fat mass or visceral fat and inflammatory gene polymorphisms; 3) to determine the predictive ability of age-related changes in inflammatory markers on subsequent ASCVD events. The proposed study will include all the Health ABC participants. For aim1 and 2, we will conduct measures of serum C-reactive protein and interleukin-6 levels every two years and sequence variants of approximately 29 important genes involved in inflammation and innate immune response. We will perform longitudinal data analyses using linear mixed-effect models. For aim 3, a prospective analysis will be conducted with Cox proportional hazard model. Understanding age-related alterations in immunosenescence and its cardiovascular deterioration is becoming increasingly important and may provide the basis for therapeutic interventions that will impact not only risk of ASCVD, but will impact morbidity and mortality from other common diseases of the elderly such as diabetes, dementia, frailty and disability. The Health ABC study, the only large cohort of community-dwelling older adults with long term follow-up and annually detailed measures of body composition, along with a wide range of functional, clinical, and laboratory data, provides a unique opportunity for studying this area of high scientific priority.