Immunosenescence: potential causes and strategies for reversal

Abstract

Age-related deterioration in immune function has been recognized in many species. In humans the clinical manifestation of such immune dysfunction is age-related increases in the susceptibility to certain infections and in the incidence of some autoimmune disease and certain cancers. Laboratory investigations reveal age-related changes in the peripheral T cell pool, in the predominant phenotype, cytokine production profiles, signalling function and in replicative ability following stimulus with antigen, mitogens or anti-CD3 antibody. These changes in the properties of peripheral T cells are thought to be causally linked to an age-associated involution in the thymus. Our analysis reveals that thymic involution is due to a change in the thymic microenvironment linked to a reduction in the level of available interleukin 7. Treatment with interleukin 7 leads to a reversal of thymic atrophy with increased thymopoiesis. This provides the potential to reverse the immune dysfunction seen in the peripheral T cell pool by replacing old cells with new output generated in the thymus. Problems to overcome in order for such an experimental therapy to be successful require careful analysis in order to provide an optimal strategy to ensure that new T cell emigrants from the thymus have a broad range of specificities and are able to enter the peripheral T cell pool.

Characterization of an interaction between fetal hemoglobin and lipid A of LPS resulting in augmented induction of cytokine production in vivo and in vitro

“…A number of groups have focused on biochemical/ physiological parameters which are altered with aging, including, but not limited to, factors such as chromosomal telomere length, cellular proteasome function, etc., and asked whether they might contribute to altered immunocompetence [41][42][43]. There is evidence that chronic oxidative stress might contribute to the immunological changes seen [43][44][45], though longevity was not increased by increasing antioxidants in the diet [46].…”

Clonal Expansions and Loss of Receptor Diversity in the Naive CD8 T Cell Repertoire of Aged Mice

“…A variety of therapeutic approaches are being tested, including thymic transplants (72) and restoration of thymic progenitor cells (73, 74) or haematopoietic stem cells (75). In addition, methods such as chemical or physical castration to lower circulating levels of sex hormones (76–78) or treatment with IL-7, alone, or in combination with LHRH agonists (67, 79, 80), have been shown to increase the rate of export from the existing, but atrophied, thymus. Finally, growth hormones to increase thymic mass (81) should be tested, as it has been shown that thymic output correlates with the size of the thymus and is independent of age (22).…”

Dietary folate improves age-related decreases in lymphocyte function

“…Undernutrition is common in the aged population, and a lower serum folate level has been correlated with decreased proliferation of T cells from elderly subjects [21]. A higher response to mitogens in vitro has been demonstrated to be associated with reduced infections [22] and a better response to vaccine [3], suggesting a physiological effect of this observation. Differences were observed between groups in the types of cells present in the spleen and MLNs.…”