What to read after Basic Biology and Clinical Impact of Immunosenescence?

Like other organ systems, the immune system does not remain unaffected by age. Work begun over three decades ago already hinted at the importance of immunity for the achievement of healthy old age. The real clinical relevance of age-related alterations in the immune system is, however, still remains controversial. This volume of ACAG contains contributions describing studies which are helping to resolve these difficulties, focussing predominantly on humans. The importance of longitudinal studies is stressed and the concept of an "immunological risk phenotype" is introduced, whereby clusters of immune parameters can predict morbidity and mortality. Current knowledge of age-associated changes in important immune system parameters are discussed in detail: T cells and NK cells, the role of cytokines and cytokine receptors, the impact of genetic factors, a critical role for the balance between inflammatory and anti-inflammatory activities within the immune system, and the role of chronic antigenic stress in determining immune parameters and overall longevity. Although all cells of the immune system show age-associated changes, it is the T cell compartment which is most severely affected. As T cells are generated primarily in the thymus, this organ must be the first focus of attention when considering T cell immunosenescence, as discussed in this volume. Peripheral T cell aging is considered in terms of alterations in signal transduction pathways required for activation of immune responses. The T cell arm is contrasted with an important compartment of the innate immune system, the neutrophil. Costimulatory requirements for T cell activation and the recent recognition of negative as well as positive T cell costimulation mediated by families of receptors originally discovered on natural killer (NK) cells is discussed. The important question of the control of apoptosis in the immune system is discussed, as well as the general question of DNA damage and repair, both nuclear and mitochondrial. A greater understanding of repair mechanisms may be important for remediation. These and other topics covered in this volume reveal the huge gains in knowledge recently acquired but highlight the enormous gaps still waiting to be filled before it can be decided whether the much maligned expression "anti-ageing medicine" will ever acquire respectability.