Study of the Association with −330T/G IL-2 in a Population of Centenarians from Centre and South Italy

Abstract

Immune response in elderly is characterised by a progressive loss of the ability to cope environmental stressors with a characteristic remodelling of cytokine network. One of the data constantly reported in literature is the decrease of IL-2 production. An IL-2 central role in the reconstitution of T cell function in vitro is largely documented. Studies on a T-->G polymorphism at -330 nt of IL-2 gene promoter region have demonstrated that T lymphocytes from 330GG homozygous subjects are able to produce in vitro higher amount of IL-2, than -330TG heterozygous or -330TT homozygous subjects. As a genetic background conditioning the maintaining of an efficient immune response would exert positive effects on healthy ageing, we have typed for 330T/G IL-2 single nucleotide polymorphism (SNP), 168 centenarians and 214 control subjects matched for age and ancestry from Centre and South Italy to check the 330GG genotype association to longevity. The statistical analysis doesn't show a significant difference of genotypic and allelic frequencies at -330 IL-2 T/G SNP among centenarians and controls. Comparing the two cohorts of subjects by extended Mantel Haenszel procedure a marginally significant trend for an increased -330TT genotype frequency was observed. Our data seem to be paradoxical considering the role attributed to a well-conserved T cell function in the successful ageing. On the other hand, in a recent study on a sample of Irish octogenarians a similar distribution of -330T/G genotype even was observed. These data suggest that a genetic background favouring an increased IL-2 production might be detrimental for longevity. On the other hand, an increase of IL-2 and other pro-inflammatory cytokine production characterise the Alzheimer's disease serum profile. All in all our data seem to suggest that reduction of -330G allele frequency might be protective for healthy ageing limiting cell mediated inflammation implied in age associated diseases.

Cytokine Serum Profile in a Group of Sicilian Nonagenarians

“…Concerning IL-2 secretion maintenance in the oldest subjects, in our previous study, no modifications of genotypic and allelic frequencies of the IL-2 functional polymorphism À330 T=G were demonstrated. [18] In our study we found a statistically significant increase in serum levels of IL-12 in nonagenarians in comparison with controls (p value ¼ 0.01) ( Table 1). Conflicting data on IL-12 production in old subjects have been published.…”

Immunosenescence and Immunogenetics of Human Longevity

“…All these phenomena have a strong genetic component, as shown by studies in old people and centenarians, which collectively established that the frequency of several polymorphisms of important genes involved in immune response and inflammation are present at a different frequency in long-lived people compared with young subjects [121,[142][143][144] . The role of an individual genetic background and predisposition for the extent of an inflammatory response is determined by the variability of genes encoding endogenous mediators involved in inflammation pathways.…”

Apolipoprotein E Genotypic Frequencies Among Down Syndrome Patients Imply Early Unsuccessful Aging for ApoE4 Carriers

“…Nonagenarian subjects, not suffering of prolonged hill or cognitive impairment in the last 5 years, were recruited according to protocols of Multicentric Study on Italian Centenarian. 16,17 Written informed consent for enrolling in the study and for personal data management was obtained for all the subjects according to Italian laws.…”