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Longitudinal studies are defining progressive alterations to the immune system associated with …

Biology Articles » Health and Medicine » Age and immunity » Genetics

- Age and immunity

The pathogenic burden, to which an individual has been or is exposed, may be linked to levels of chronic inflammation and to increased risk of age-related diseases. This will be influenced by genetic factors affecting the capacity of the host to control the pathogen-induced inflammatory response. Calogero Caruso (University of Palermo) suggested that within the inflammatory network, the most important node of the net is represented by CD14, the main receptor for Gram-negative endotoxin, and its co-receptor, TLR4, responsible for activating intracellular signalling pathways. Several functional polymorphisms have been described in these genes associated with age-related disease. Thus, the intensity of the genetically-determined inflammatory response against pathogens or their antigens might play a major role in determining the magnitude of inflammation and subsequent clinical outcome. The presence of gene polymorphisms with pro-inflammatory associations may fuel the inflammatory response of macrophages to gram-negative infection, promoting pro-inflammatory status and clinical setting of the inflammatory diseases [11,12]. This implies that people genetically predisposed to a weak inflammatory activity have less risk of developing age-related diseases and genetic polymorphisms responsible for a low inflammatory response might therefore result in an increased chance of a long life-span in a modern environment with a reduced pathogen burden.

Elisavetta Naumova (University of Sofia) studying the Bulgarian population focused on the relevance of HLA and cytokine genotype profiling as predictors of successful ageing. The analysis showed statistically significantly increased frequencies in elderly individuals and in families with long-lived members of HLA haplotypes such as DRB*11 and DRB*16. However, the pro-inflammatory cytokine gene polymorphisms for IL-2, IL-6, IFN-γ did not differ significantly between elderly and controls, but differences were observed for IL-10, TGF-β, and TNF-α genes, supporting a role of HLA and cytokine genes in successful ageing [13].

Another factor with a genetic basis discussed in this session, which could be contributing to T cell immunosenescence and chronic inflammation in the elderly, is the dysregulation of zinc homeostasis (Marco Malavolta, INRCA, Ancona). Preliminary results from the EU ZINCAGE Project, indicate that zinc dyshomeostasis, characterized by high levels of expression of metallothioneins (MT) associated with plasma zinc deficiency and impaired release of zinc at the intracellular level, may occur mostly in aged T cells of subjects carrying the C allele of the 647 A/C MT1A SNP, especially when associated with a pro-inflammatory cytokine profile. In contrast, carriers of the A allele, perhaps through a better regulation of zinc homeostasis, have a greater likelihood of longer life [14]. Careful zinc supplementation my therefore also represent a possible intervention to help maintain immunological integrity, an approach that the ZINCAGE project is currently testing.

Daniel Remondini (Bologna University) presented data on T-cell profiling over lifespan in humans, suggesting a possible global response of gene activity in ageing.

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