The participating NIH Institutes and Centers invite applications to address both the origins and the effects of low level chronic inflammation in the onset and progression of age-related diseases and conditions. Chronic inflammation, as defined by elevated levels of both local and systemic cytokines and other pro-inflammatory factors, is a hallmark of aging in virtually all higher animals including humans and is recognized as a major risk factor for developing age-associated diseases. The spectra of phenotypes capable of generating low-level chronic inflammation and their defining mediators are not clear. Further, a clear understanding of how chronic inflammation compromises the integrity of cells or tissues leading to disease progression is lacking. The role of dietary supplements and/or nutritional status in chronic inflammation in age-related disease is also poorly studied. Thus, there is a critical need to establish the knowledge base that will allow a better understanding of the complex interplay between inflammation and age-related diseases. Applications submitted to this FOA should aim to clarify the molecular and cellular basis for the increase in circulating inflammatory factors with aging, and/or shed light on the cause-effect relationship between inflammation and disease, using pre-clinical (animal or cellular based) models.