aruso C

Age-Related Inflammation: the Contribution of Different Organs, Tissues and Systems. How to Face it for Therapeutic Approaches

A typical feature of ageing is a chronic, low-grade inflammation characterized by a general increase in the production of pro-inflammatory cytokines and inflammatory markers (inflamm-ageing). This status may slowly damage one or several organs, especially when unfavorable genetic polymorphisms and epigenetic alterations are concomitant, leading to an increased risk of frailty together with the onset of age-related chronic diseases. The contribution of different tissues (adipose tissue, muscle), organs (brain, liver), immune system and ecosystems (gut microbiota) to age-related inflammation (inflamm-ageing) will be discussed in this review in the context of its onset/progression leading to site-restricted and systemic effects. Moreover, some of the possible strategies and therapies to counteract the different sources of molecular mediators which lead to the age-related inflammatory phenotype will be presented.

B Cells Compartment in Centenarian Offspring and Old People

Immunosenescence is considered a major contributory factor to the increased frequency of morbidity and mortality among elderly. On the other hand centenarians are considered the best example of successful ageing. To gain insight into mechanisms of immunosenescence and its clinical relevance, a possible model is represented by centenarians and/or their offspring. Nowadays centenarians are not more a curiosity, but in Europe are 1/8000 inhabitants and it has been demonstrated that the centenarian offspring, who are typically in their 70s and 80s, have a survival advantage when compared with age-matched controls whose parents died at an average life expectancy. Then again, studies on immunosenescence focus mainly on T cell impairment, although B cells are also affected. So, in the present preliminary report, we have studied B cell compartment in two classes of individuals, old people and centenarian offspring. B cell compartment was analysed using IgD and CD27 antibodies which characterize naïve B cells (IgD(+) CD27(-)), memory unswitched B cells (IgD(+)CD27(+)), memory switched B cells(IgD(-)CD27(+)) and double negative B cells (DN) (IgD(-)CD27(-)), i.e. exhausted memory cells. As expected, in both cohorts we observed a decreased B cell count. However, in centenarian offspring, naïve B cells are more abundant whereas exhausted memory cells (DN B cells, IgD(-)CD27(-)) do not show the increase that we have previously demonstrated in healthy elderly donors. These data are similar to that found in previously experiments on young subjects. So, our preliminary results show that centenarian offspring do not have the typical trend of memory/naive B cell subsets observed in elderly people and this is in agreement with the higher levels of IgM in the serum of centenarian offspring in comparison with data obtained in age-matched controls. This reservoir of naive B cell might be one of the causes that make centenarian offspring able to keep fighting off new infections, hence prolonging their life. So, B cell subset changes could represent a hallmark of successful or unsuccessful ageing and could be used as a biomarker of human life span, potentially useful for the evaluation of anti-ageing treatment.

Variants in Antiviral Genes are Risk Factors for Cognitive Decline and Dementia

A gene association study of factors regulating antiviral response such as interferon (IFN)-λ3, also known as IL-28B, mediator complex (Med) 23, and interferon regulatory factor (IRF) 7 with cognitive deterioration and Alzheimers disease (AD) was performed. Differences in the TT genotype distribution of IL-28B single nucleotide polymorphism (SNP) between AD patients and controls were found. The GG genotype of Med23 gene appeared to influence the progression of the disease, being more frequent in the APOE ɛ4 negative elderly that developed AD during the five year follow-up. Leukocyte positivity for Epstein Barr virus (EBV) and human herpes virus (HHV)-6 DNA was analyzed. Med23 GG genotype correlated with the positivity to HHV-6 DNA. EBV and HHV-6 plasma IgG levels were also investigated and EBV IgG levels were increased in AD with the IRF7 GG genotype. A differential genetic background in genes regulating anti-virus responses was associated with an increased risk of cognitive decline and AD. EBV and HHV-6 appeared to be risk factors for AD in genetically susceptible elderly.