Cytomegalovirus seropositivity is associated with glucose regulation in the oldest old. Results from the Leiden 85-plus Study

Background: Cytomegalovirus (CMV) infection has been reported to contribute to the pathogenesis of type 1 diabetes and post-transplantation diabetes. However, CMV infection has not been evaluated as a possible risk factor for type 2 diabetes. Our aim was to investigate potential associations between CMV seropositivity, CMV IgG antibody level and glucose regulation in the oldest old.Results: CMV seropositive subjects were more likely to have type 2 diabetes (17.2% vs 7.9%, p = 0.016), had a higher level of HbA1c (p = 0.014) and higher non-fasting glucose (p = 0.024) in the oldest olds. These associations remained significant after adjustment for possible confounders. CMV IgG antibody level was not significantly associated with glucose regulation (all p > 0.05).Conclusions: In the oldest old, CMV seropositivity is significantly associated with various indicators of glucose regulation. This finding suggests that CMV infection might be a risk factor for the development of type 2 diabetes in the elderly

Early-life environment influencing susceptibility to cytomegalovirus infection: evidence from the Leiden Longevity Study and the Longitudinal Study of Aging Danish Twins

SUMMARYHuman cytomegalovirus (CMV) is a common herpesvirus establishing lifelong persisting infection, which has been implicated in immunosenescence and mortality in the elderly. Little is known about how and when susceptibility to CMV infection is determined. We measured CMV seroprevalence in two genetically informative cohorts. From the Leiden Longevity Study (LLS) we selected long-lived sib-pairs (n=844) and their middle-aged offspring and the offspring's partners (n=1452). From the Longitudinal Study of Aging Danish Twins (LSADT) 604 (302 pairs) same-sex monozygotic (MZ) and dizygotic (DZ) twins aged 73-94 years were included (n=302 pairs). Offspring of the long-lived LLS participants had significantly lower seroprevalence of CMV compared to their partners (offspring: 42% vs. partners: 51%, P=0·003). Of 372 offspring living with a CMV-positive partner, only 58% were infected. The corresponding number for partners was 71% (P<0·001). In the LSADT, MZ and DZ twins had high and similar CMV-positive concordance rates (MZ: 90% vs. DZ: 88%, P=0·51) suggesting that shared family environment accounts for the similarity within twin pairs. Our findings suggest that susceptibility to CMV infection - even under continuous within-partnership exposure - appears to be more strongly influenced by early-life environment than by genetic factors and adult environment.Pathophysiology, epidemiology and therapy of agein

Immunosenescence and Cytomegalovirus: where do we stand after a decade?

AbstractSince Looney at al. published their seminal paper a decade ago it has become clear that many of the differences in T cell immunological parameters observed between young and old people are related to the age-associated increasing prevalence of infection with the persistent beta-herpesvirus HHV-5 (Cytomegalovirus). Ten years later, studies suggest that hallmark age-associated changes in peripheral blood T cell subset distribution may not occur at all in people who are not infected with this virus. Whether the observed changes are actually caused by CMV is an open question, but very similar, rapid changes observed in uninfected patients receiving CMV-infected kidney grafts are consistent with a causative role. This meeting intensively discussed these and other questions related to the impact of CMV on human immune status and its relevance for immune function in later life.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A Consideration of Biomarkers to be Used for Evaluation of Inflammation in Human Nutritional Studies

To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammatio

Inflammation, genetic background and longevity

Ageing is an inexorable intrinsic process that affects all cells, tissues, organs and individuals. Due to a diminished homeostasis and increased organism frailty, ageing causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. Actually, it is characterized by a state of reduced ability to maintain health and general homeodynamics of the organism.Alarge part of the ageing phenotype is explained by an imbalance between inflammatory and anti-inflammatory networks, which results in the low grade chronic pro-inflammatory status of ageing, ‘‘inflamm-ageing’’. It is strictly linked to immunosenescence, and on the whole they are the major contributory factors to the increased frequency of morbidity and mortality among elderly. Inflammageing is compatible with longevity; even if centenarians have an increased level of inflammatory mediators in comparison to old subjects and they are very frail, they also have high level of anti-inflammatory cytokines together with protective genotypes. Actually, data on case control studies performed in Italian centenarians suggest that a pro-inflammatory genotype is unfavourable to reach extreme longevity in good health and likely favours the onset of age-related diseases such as cardiovascular diseases and Alzheimer’s disease, the leading causes of mortality and disability in the elderly. However, many associations between gene variants and longevity have been found only in Italian population. This should not be unexpected, since ageing and longevity are complex traits resulting not only and not exclusively from genetics, but rather from the interactions between genetics, environment and chance

Molecular Clusters in Mesoporous Materials as Precursors to Nanoparticles of a New Lacunar Ternary Compound PdxMoyP

Bimetallic clusters of composition Pd2Mo2(g5-C5H5)2(l3-CO)2(l2-CO)4 (PR3)2 (R = ethyl or phenyl) were incorporated by impregnation from solution into two different silica matrices, amorphous xerogels and ordered SBA-15, and a study of their thermal decomposition under a reducing atmosphere is reported. With both matrices, a suitable thermal treatment afforded nanoparticles of a new bimetallic phosphide. Although nanoparticles of composition PdxMoyP, isostructural with Mo3P, were formed in both matrices, they were more uniformly distributed in the SBA-15 framework and showed a narrower size distribution. The samples have been characterized by powder XRD, chemical analysis, FT-IR spectroscopy, TEM and electron tomography (3D TEM)

Mechanisms of immunosenescence

On April 7,8, 2009 a Symposium entitled "Pathophysiology of Successful and Unsuccessful Ageing" took place in Palermo, Italy. Here, the lectures of G. Pawelec, D. Dunn-Walters and. G. Colonna-Romano on T and B immunosenescence are summarized. In the elderly, many alterations of both innate and acquired immunity have been described. Alterations to the immune system in the older person are generally viewed as a deterioration of immunity, leading to the use of the catch-all term immunosenescence. Indeed, many immunological parameters are often markedly different in elderly compared to young people, and some, mostly circumstantial, evidence suggests that retained function of both innate and acquired immunity in the elderly is correlated with health status. What is often not clear from studies is how far immune dysfunction is a cause or an effect. A better understanding of immunosenescence and mechanisms responsible for proven deleterious changes is needed to maintain a healthy state in later life and to design possible therapeutic interventions