Immunosenescence of ageing.

Abstract

Ageing is a complex process that negatively impacts the development of the immune system and its ability to function. The mechanisms that underlie these age-related defects are broad and range from defects in the haematopoietic bone marrow to defects in peripheral lymphocyte migration, maturation and function. The thymus is a central lymphoid organ responsible for production of naïve T cells, which play a vital role in mediating both cellular and humoral immunity. Chronic involution of the thymus gland is thought to be one of the major contributing factors to loss of immune function with increasing age. It has recently been demonstrated that thymic atrophy is mediated by a shift from a stimulatory to a suppressive cytokine microenvironment. In this review we present an overview of the morphological, cellular and biochemical changes that have been implicated in the decline of thymic and peripheral immune function with ageing. We conclude with the clinical implications of age-associated immunosenescence to vaccine development for tumours and infectious disease. A fundamental understanding of the complex mechanisms by which ageing attenuates immune function will enable translational research teams to develop new therapies and vaccines specifically aimed at overcoming these defects in immunological function in the aged.