Successful immunosenescence and the remodelling of immune responses with ageing

Abstract

In recent decades, major theoretical and technological advances have been achieved in the field of immunology. These have allowed the scientific community to analyse the immune system in a much more sophisticated manner than was possible even 20 years ago. Moreover, great theoretical changes have also occurred in gerontology-in particular, the hypothesis has been put forward that ageing and diseases are two different phenomena, and that successful ageing, i.e. ageing in good psychophysical conditions, is really possible for most humans and animals. Immunosenescence was then carefully investigated, either in selected healthy people of advanced age or in the oldest old people, such as healthy centenarians. The main results showed that most immune parameters are indeed well preserved even at this far advanced age. This paper deals with some of the most important theoretical problems of immunosenescence. An immunological tenet was that the most important phenomenon of immunosenescence is the involution of the thymus. In most textbooks and papers it is taken for granted that the thymus starts its involution immediately after puberty. When people aged 60-65 were considered old, it was not difficult to think that they could live for the rest of their life with a fully involuted thymus. The findings on centenarians challenge this tenet, as they have only a small reduction of T lymphocytes, and a relatively normal number of virgin and memory T cells, together with a functional T cell repertoire. Other observations reported here on centenarians, concerning the activity of B lymphocytes and the cytokine network, as well as those on the well-preserved innate immunity and the cells' capability of undergoing proliferation after appropriate stimuli, suggest that complex immune changes occur with age, but also indicate that we have to modify our attitude, to grasp the new scenario which is emerging. Immunosenescence can no longer be considered as a unidirectional deterioration, and this complex phenomenon is much better described by terms such as 'remodelling', 'reshaping' or 'retuning'.

Is thymus redundant after adulthood?

“…This regulation of peripheral T cell pool by thymic migrants is strongly supported by the findings on centenarians that show a relatively normal number of naive and memory T cells, together with a functional T cell repertoire [85]. However, it is still not clear how thymic export is regulated as to date no firm feedback loops have been defined between events in the peripheral T cell pool feeding back on the thymus to increase thymic output [86].…”

Ascitic Growth of a Spontaneous Transplantable T Cell Lymphoma Induces Thymic Involution

“…Only a small reduction in T lymphocytes with age and a relatively normal number of naive and memory T cells together with a functional T cell repertoire has been reported [35]. Moreover, the thymus has been shown to play a determining role in the establishment of longterm cytolytic T cell memory [36,37].…”

Aging and Immune Function: Molecular Mechanisms to Interventions

“…Studies conducted in humans have demonstrated an increase in overall numbers of circulating NK cells, with little or no loss in cytolytic activity, either toward sensitive tumor targets or when non-MHC restricted activity was assessed (105,106). A detailed phenotypic analysis of peripheral blood mononuclear cell (PBMC) demonstrated little or no age-related alteration in NK cell activity in healthy subjects recruited per strict SENIEUR protocol adherence (206).…”