Signal transduction changes in granulocytes and lymphocytes with ageing.

It is well known that the immune response declines with ageing. However, the exact cause of this decline is still unknown. In recent years signal transduction events leading to the transmission of a signal from the cell surface to the nucleus have been extensively studied in various cell systems. These studies have indicated that an alteration in signal transduction occurs with ageing. It is not possible to identify a single age-sensitive step in this sequence, but rather a series of deficiencies contributing to the decline in competency of aged lymphocytes and granulocytes to undergo normal activation. Thus, signal transduction events such as calcium mobilization, phosphatidylinositol breakdown, accumulation of proto-oncogene transcripts, expression of activation markers, and synthesis of new proteins are deficient in the aged. Other events in signal transduction have been much less studied such as protein tyrosine kinase activity and G-protein functions. alterations in these various intracellular signalling events may fundamentally influence the functional activity of lymphocytes and granulocytes in the aged, as suggested by several investigations performed in recent years and reviewed in the subsequent sections. Future study on the signal transduction pathways using well-defined experimental models and healthy individuals should help to elucidate the molecular basis of immunosenescence and to develop effective approaches for reducing age-associated deficits and thereby reducing the incidence of age-associated diseases.