Aging and Immune Dysfunction

The number of people over the age of 65 is increasing, a trend that will continue in the foreseeable future. A considerable volume of evidence exists to support the contention that immune system function deteriorates as human beings age. The decline in immune function, frequently called immunosenescence, is often attributed to thymic involution and the associated impairments in T-cell function. More recent evidence points to the decline in antigen naive cells and the accumulation of regulatory T cells (Treg or suppressor T cells), which appears to coincide with aging. Innate immunity also appears to decline with age, with impaired dendritic cell and macrophage function. These cells are responsible for presenting antigen to the adaptive arm of the immune system. B-cell function, and the associated antibody production is frequently shown to be normal in older individuals, but overall, B-cell function is impaired by the decline in antibody-producing plasma cells, which is functionally evident in the impaired response to vaccines in the elderly.

Aging is linked to an increased number of infections, autoimmune diseases, and cancers—many likely attributable to a decline in host defense. More recently, aging has been linked to a hyperinflammatory state, which has been implicated in the risk of cardiovascular disease, diabetes, and other chronic diseases. In 2000, Claudio Franceschi coined the term inflamm-aging to describe the coincident increase in morbidities and inflammation observed in older persons. Franceschi and coworkers suggested that inflammaging is caused by lifelong exposure to acute and chronic infections and the resulting cumulative antigenic burden. Simply put, a lifetime of fighting infection takes its toll on the immune system.

In this entry, various aspects of declines in the immune system with aging and potential comorbid associations with inflammation are described. Recent research on the anti-inflammatory actions of regular exercise are contrasted with Franceschi's inflammaging model to allow for the possibility that aging per se is not the cause of all “age-related” phenomena.