Pathways to a robust immune response in the elderly.

Circumstantial evidence suggests that infectious disease is the major cause of morbidity and mortality in the elderly, and immune-system dysfunction may contribute to this finding. Because innate and humoral immunity seem to be relatively unaffected by aging and because the T-cell compartment shows marked age-associated alterations, this article focuses on the association between T cells and aging. Longitudinal studies suggest that immune parameters, which predominantly are related to T cells, can be clustered to yield an IRP that is predictive of mortality in the elderly. Determining the IRP also may be helpful in younger individuals, particularly those under chronic antigenic stress (eg, patients with cancer or chronic infections) who experience premature aging of the immune system. Some changes in T cells can be modeled in clonal cultures in vitro to discover new biomarkers of immune aging. These biomarkers, which need to be validated in vivo, could be used to refine IRP. Interventions to selectively target changes that are identified as part of IRP may improve the health and quality of life of the elderly, reduce healthcare costs, and avoid potential unwanted side effects of global intervention approaches, such as triggering or exacerbating autoimmunity and inflammation.