Intracellular signalling pathways: targets to reverse immunosenescence

Abstract

Ageing is a very complex process, the result of the dysregulation of multiple systems interacting in many ways. A prominent change occurring with ageing is related to the architecture and functioning of the immune system, viewed commonly as detrimental and termed 'immunosenescence'. However, age-associated changes may also lead to increased function in certain respects, which can be viewed as adaptive. None the less, on balance it is well-recognized that immunosenescence is accompanied by the low-grade inflammation observed commonly in elderly people, which has been dubbed 'inflamm-ageing'. The exact cause and significance of all these changes is not clear, but there is a consensus that they are related to the occurrence of chronic non-infectious age-associated disease, as well as increased susceptibility to infections. Alterations to immune cell signalling may be a prominent cause of malfunctioning immunity. Emerging attempts to reverse immunosenescence have recently targeted the signalling pathways in various different cell types of the immune system. Here, we review and discuss alterations in the signalling pathways of immune cells with ageing and consider current targets and means to modulate altered functions. We discuss the potential dangers as well as the benefits of these interventions, and consider future approaches to this problem.

Keywords: adaptive immunity; aging; immunosenescence; innate immunity; lipid rafts; signalling pathways.

Figure 1

Different signalling pathway targets already used for interventions to reverse immunosenescence. Immune cells use receptor‐mediated signalling pathways to respond to their ligands. With ageing, the changes in the signalling pathways may lead to changes in immune cell functions of the innate and the adaptive immune response. To improve the functioning of the immune cells with ageing, these signalling pathways seem to be good targets. The main targets used in various studies in vitro (*) and in vivo (†) are indicated. ? Suggests that other possible targets not yet explored in the context of immunosenescence.