Aging, immunity, and cancer
ABSTRACT Age is the most important risk factor for tumorigenesis. More than 60% of new cancers and more than 70% of cancer deaths occur in elderly subjects >65 years. The immune system plays an important role in the battle of the host against cancer development. Deleterious alterations occur to the immune response with aging, termed immunosenescence. It is tempting to speculate that this waning immune response contributes to the higher incidence of cancer, but robust data on this important topic are few and far between. This review is devoted to discussing state of the art knowledge on the relationship between immunosenescence and cancer. Emerging understanding of the aging process at the molecular level is viewed from the perspective of this increased tumorigenesis. We also consider some of the most recent means to intervene in the modulation of immunosenescence to increase the ability of the immune system to fight against tumors. Future research will unravel new aspects of the immune response against tumors which will be modulable to decrease the burden of cancer in elderly individuals.
- SourceAvailable from: Sanjay H Chotirmall
Mediators of Inflammation 06/2015; 2015(692546):1. · 3.24 Impact Factor
- "Additionally, there is a reduction in host defense mechanisms including macrophage phagocytosis, ineffective chemotaxis, decreased bactericidal function of neutrophils, and altered capability of dendritic and natural killer cells . " Inflamm-aging " often takes place and is associated with immunosuppression and low grade inflammation . When secondary pulmonary infection occurs as a result of impaired host response, secondary inflammation develops . "
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- "In addition to viruses, other stimulating agents may be present. This is perhaps the case for the continuous emergence of cancer antigens independent of the overt presence of clinical cancer (61). Indeed, many cancers such as advanced renal carcinoma, head and neck cancers, and melanomas are associated with the presence of late-differentiated CD8+ T cells (62, 63). "
ABSTRACT: Aging is associated with a dysregulation of the immune response, loosely termed "immunosenescence." Each part of the immune system is influenced to some extent by the aging process. However, adaptive immunity seems more extensively affected and among all participating cells it is the T cells that are most altered. There is a large body of experimental work devoted to the investigation of age-associated differences in T cell phenotypes and functions in young and old individuals, but few longitudinal studies in humans actually delineating changes at the level of the individual. In most studies, the number and proportion of late-differentiated T cells, especially CD8+ T cells, is reported to be higher in the elderly than in the young. Limited longitudinal studies suggest that accumulation of these cells is a dynamic process and does indeed represent an age-associated change. Accumulations of such late-stage cells may contribute to the enhanced systemic pro-inflammatory milieu commonly seen in older people. We do not know exactly what causes these observed changes, but an understanding of the possible causes is now beginning to emerge. A favored hypothesis is that these events are at least partly due to the effects of the maintenance of essential immune surveillance against persistent viral infections, notably Cytomegalovirus (CMV), which may exhaust the immune system over time. It is still a matter of debate as to whether these changes are compensatory and beneficial or pathological and detrimental to the proper functioning of the immune system and whether they impact longevity. Here, we will review present knowledge of T cell changes with aging and their relation to chronic viral and possibly other persistent infections.Frontiers in Immunology 09/2013; 4(article 271):271. DOI:10.3389/fimmu.2013.00271
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- "Ageing of the adaptive immune system is also associated with the increased proportion of effector/memory (CD45RO+) at the expense of naïve (CD45RA+) lymphocytes within the CD4+ population . Thus, it was feasible that the observed changes in the CCS expression in the CD4+ cells of the elderly would be due to rising proportion of the CD45RO+ cells. "
ABSTRACT: Ubiquitous system of regulatory, calcium-dependent, cytoplasmic proteases -- calpains -- and their endogenous inhibitor -- calpastatin -- is implicated in the proteolytic regulation of activation, proliferation, and apoptosis of many cell types. However, it has not been thoroughly studied in resting and activated human lymphocytes yet, especially in relation to the subjects' ageing process. The CALPACENT project is an international (Polish-Italian) project aiming at verifying the hypothesis of the role of calpains in the function of peripheral blood immune cells of Polish (Pomeranian) and Italian (Sicilian) centenarians, apparently relatively preserved in comparison to the general elderly population. In this preliminary report we aimed at establishing and comparing the baseline levels of expression of mu- and m-calpain and calpastatin in various, phenotypically defined, populations of human peripheral blood lymphocytes for healthy elderly Sicilians and Poles, as compared to these values observed in young cohort. We have found significant differences in the expression of both mu- and m-calpain as well as calpastatin between various populations of peripheral blood lymphocytes (CD4+, CD8+ and CD19+), both between the age groups compared and within them. Interestingly, significantly higher amounts of mu- and m-calpains but not of calpastatin could be demonstrated in the CD4+CD28- and CD8+CD28- lymphocytes of old subjects (but not in the cells of young individuals), as compared to their CD28+ counterparts. Finally, decreased expression of both calpains in the elderly T cells is not related to the accumulation of effector/memory (CD45RO+) cells in the latter, as the expression of both calpains does not differ significantly between the naive and memory T cells, while is significantly lower for elderly lymphocytes if both populations are taken separately. Observed differences in the amounts of CCS member proteins between various populations of lymphocytes of young and elderly subjects may participate in the impaired proliferative activity of these cells in the elderly.Immunity & Ageing 07/2013; 10(1):27. DOI:10.1186/1742-4933-10-27 · 3.54 Impact Factor