Factors that may impact on immunosenescence: an appraisal

Abstract

The increasing ratio of ageing population poses new challenges to healthcare systems. The elderly frequently suffer from severe infections. Vaccination could protect them against several infectious diseases, but it can be effective only if cells that are capable of responding are still present in the repertoire. Recent vaccination strategies in the elderly might achieve low effectiveness due to age-related immune impairment. Immunosenescence affects both the innate and adaptive immunity.Beside individual variations of genetic predisposition, epigenetic changes over the full course of human life exert immunomodulating effects. Disturbances in macrophage-derived cytokine release and reduction of the natural killer cell mediated cytotoxicity lead to increased frequency of infections. Ageing dampens the ability of B cells to produce antibodies against novel antigens. Exhausted memory B lymphocyte subsets replace naïve cells. Decline of cell-mediated immunity is the consequence of multiple changes, including thymic atrophy, reduced output of new T lymphocytes, accumulation of anergic memory cells, and deficiencies in cytokines production. Persistent viral and parasitic infections contribute to the loss of immunosurveillance and premature exhaustion of T cells. Reduced telomerase activity and Toll-like receptor expression can be improved by chemotherapy. Reversion of thymic atrophy could be achieved by thymus transplantation, depletion of accumulated dysfunctional naive T cells and herpesvirus-specific exhausted memory cells. Administration of interleukin (IL)-2, IL-7, IL-10, keratinocyte growth factor, thymic stromal lymphopoietin, as well as leptin and growth hormone boost thymopoiesis. In animals, several strategies have been explored to produce superior vaccines. Among them, virosomal vaccines containing polypeptide antigens or DNA plasmids as well as new adjuvanted vaccine formulations elicit higher dendritic cell activity and more effective serologic than conventional vaccines responses in the elderly. Hopefully, at least some of these approaches can be translated to human medicine in a not too far future.

Potentially fatal complications for elderly patients after laparoscopy-assisted distal gastrectomy

“…However, the definition of complication severities after LAG in the elderly was not strictly defined in these previous reports. Severe postoperative complications can easily become fatal in elderly patients as the result of age-related decline in immune functions, which could increase the prevalence and severity of infectious diseases in elderly patients [29][30][31][32]. Therefore, we analyzed postoperative complications depending on their severity and studied risk factors for severe complications in elderly LADG cases.…”

Dysfunction of dendritic cells in aged C57BL/6 mice leads to failure of natural killer cell activation and of tumor eradication

“…Increasing evidence shows aging affects many cells in both innate immunity and adaptive immunity (9). For example, impairment of DC and macrophage functions, including phagocytic activity, cytokine secretion, wound repair, and antigen presentation, were observed (10,11).…”

Reversing T cell immunosenescence: why, who, and how

“…The decreased number of naïve T cells Production and maintenance of the diverse peripheral naïve T cell repertoire are critical to the normal function of the immune system (Weiskopf et al 2009;Ongrádi and Kövesdi 2010). In the older adults, there is a decrease both in the diversity and functional integrity of the CD4+ and CD8+ T cells subsets which contribute to a decreased ability to respond adequately to reinfection (Naylor et al 2005) and a poorer vaccine effectiveness (Lang et al 2011a).…”

“…Indeed, the age-related changes of the immune system, commonly termed immunosenescence (Weiskopf et al 2009;Ongrádi and Kövesdi 2010), contribute to the increased susceptibility of older adults to develop not only infectious diseases, but cancer, Alzheimer's diseases, osteoporosis, and autoimmunity (Ginaldi et al 2005;Lang et al 2010b;Fulop et al 2011).…”

“…Thymic atrophy and decreased thymopoiesis are active processes mediated by the upregulation of thymosupressive cytokines (i.e., interleukin-IL-6, leukemia inhibitory factor-LIF, and oncostatin M-OSM) in aged human being and mice thymus tissue (Sempowski et al 2000;Ongrádi and Kövesdi 2010), while IL-7 production by stromal cell is significantly decreased (Andrew and Aspinall 2002;Ortman et al 2002). IL-7 is necessary for thymopoiesis, promoting cell survival by maintaining the anti-apoptotic protein Bcl-2 and inducing V-DJ recombination (see Fig.…”