A radical view of immunosenescence: Does chronic redox depletion interfere with immune cell signalling and function?

Many changes occur in the aging immune system, which culminate in its functional decline, but the underlying mechanisms have proved difficult to define. Wick & Grubeck-Loebenstein, (1) have recently classified the changes in function as either primary " those that occur in perfectly healthy older individuals " as the result of " an age dependent intrinsic decline of immune responsiveness " or secondary " those that are due to underlying disease or various environmental factors including diet, drug intake, physical activity, etc ". Both types of alteration are important when considering immune dysfunction in the elderly which seem to be centred on the loss of cell mediated immunity, in particular the activity of CD4 helper T lymphocytes. The most apparent primary change is the gradual shift of these cells from a naïve to a memory phenotype, while secondary changes include an accumulation of defects in intracellular signalling pathways. These have interesting parallels in chronic inflammatory diseases, changes which may result from oxidative stress. This work will review immune changes in aging, with particular focus on those involving signal transduction pathways and suggest how the oxidation of key proteins in this pathway may play a role in the dysfunction of the immune system in elderly individuals.