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

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

Income and Markers of Immunological Cellular Aging

Socioeconomic disadvantage may contribute to poor health through immune-related biological mechanisms. We examined the associations between socioeconomic status, as measured by annual household income, and T-cell markers of aging, including the ratios of CD4 and CD8 effector cells to naïve cells (E:N ratio) and the CD4:CD8 T-cell ratio. We hypothesized that participants with a lower income would have higher E:N ratios and lower CD4:CD8 ratios compared to participants with a higher income, and that these associations would be partially mediated by elevated cytomegalovirus (CMV) IgG antibody levels, a virus implicated in aging and clonal expansion of T-cells

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

CD43-independent augmentation of mouse T-cell function by glycoprotein cleaving enzymes

Previous work has shown that the function of mouse CD4 + T cells can be augmented by an enzyme, O -sialoglycoprotein endopeptidase (OSGE), which cleaves surface CD43, suggesting the idea that the high levels of glycosylated CD43 found on T cells from aged mice may contribute to immune senescence. New results now show that OSGE improves T-cell function even in mice lacking CD43, showing that other glycoproteins must contribute to the OSGE effect on function. Evaluation of other enzymes found two whose ability to stimulate CD4 activation was higher in aged than in young T cells. One of these, PNGase F, is a glycosidase specific for N-linked glycans, and the other, ST-Siase(2,3) from Salmonella typhimurium , is specific for α2,3-linked terminal sialic acid residues. Parallel lectin-binding experiments showed that removal of α2,3-linked sialic acid residues vulnerable to PNGase F and ST-Siase(2,3) was also greater in old than in young T cells. The preferential ability of PNGase F and ST-Siase(2,3) to improve the function of T cells from aged mice may involve cleavage of glycoproteins containing α2,3-linked sialic acid residues on N-linked or O-linked glycans or both.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75621/1/j.1365-2567.2006.02419.x.pd

PTSD is associated with an increase in aged T cell phenotypes in adults living in Detroit

Psychosocial stress is thought to play a key role in the acceleration of immunological aging. This study investigated the relationship between lifetime and past-year history of post-traumatic stress disorder (PTSD) and the distribution of T cell phenotypes thought to be characteristic of immunological aging

Environmental and cultivar variability in composition, content and biological activity of phenolic acids and alkylresorcinols of winter wheat grains from a multi-site field trial across Europe

Different factors such as the genotype, environmental conditions, temperature stress, solar radiation and others can influence the phytochemical status of plants. The concentration of phenolic acids and alkylresorciols (ARs) as well as their chemical composition and biological activity have been determined in twelve winter wheat cultivars grown at eight European locations. This was the first winter wheat multi-location field trial of the European Consortium for Open Field Experimentation (ECOFE). Extracts from grain were analyzed using a UPLC-PDA-ESI-MS system (phenolic acids), UPLC-PDA-MS/MS (alkylresorcinols) and TLC-DPPH center dot test with ImageJ program (antiradical activity). The phenolic acid profile consisted of five hydroxybenzoic acid and four hydroxycinnamic acid derivatives, among which ferulic and sinapic acids were predominated. The ARs profile consisted of nine AR derivatives, among which 5-n-heneicosylresorcinol (C21:0) and 5-n-nonadecanylresorcinol (C19:0) were predominated. Our study showed significant differences in phenolic acids and AR content between wheat cultivars, as well as between locations. We observed a positive correlation between the biological activity of extracts and the total amount of phenolic acids and ARs. Two cultivars, Chambo and Julius (average of all sites) and samples from the Spanish site (average of all cultivars) showed the highest content and composition of nutritional substances

Environmental and cultivar variability in composition, content and biological activity of phenolic acids and alkylresorcinols of winter wheat grains from a multi-site field trial across Europe

Different factors such as the genotype, environmental conditions, temperature stress, solar radiation and others can influence the phytochemical status of plants. The concentration of phenolic acids and alkylresorciols (ARs) as well as their chemical composition and biological activity have been determined in twelve winter wheat cultivars grown at eight European locations. This was the first winter wheat multi-location field trial of the European Consortium for Open Field Experimentation (ECOFE). Extracts from grain were analyzed using a UPLC-PDA-ESI-MS system (phenolic acids), UPLC-PDA-MS/MS (alkylresorcinols) and TLC-DPPH• test with ImageJ program (antiradical activity). The phenolic acid profile consisted of five hydroxybenzoic acid and four hydroxycinnamic acid derivatives, among which ferulic and sinapic acids were predominated. The ARs profile consisted of nine AR derivatives, among which 5-n-heneicosylresorcinol (C21:0) and 5-n-nonadecanylresorcinol (C19:0) were predominated. Our study showed significant differences in phenolic acids and AR content between wheat cultivars, as well as between locations. We observed a positive correlation between the biological activity of extracts and the total amount of phenolic acids and ARs. Two cultivars, Chambo and Julius (average of all sites) and samples from the Spanish site (average of all cultivars) showed the highest content and composition of nutritional substances.info:eu-repo/semantics/publishedVersio