http://www.immunityageing.com The latest research articles published by Immunity & Ageing 2010-07-05T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Background: Leukotrienes are pro-inflammatory lipid mediators, which are important in asthma leading to its characteristic features of airway bronchoconstriction, wheezing, increased mucus secretion and decreased mucociliary clearance. Aging results in changes in immune function and we have previously demonstrated age-related differences in levels of neutrophil elastase, MMP-9, and IL-8 in asthma subjects. We sought to determine whether leukotriene levels differed between young and older asthmatics. Results: In this pilot study, we measured leukotriene B4 (LTB4) and leukotriene C4 (LTC4) production in neutrophils and eosinophils, respectively, stimulated with calcium ionophore in vitro. Sputum samples were analyzed for LTB4 and cysteinyl leukotrienes (cysLT). Analysis of data was performed as a comparison between the younger and older age groups. Sputum analysis revealed a tendency towards a higher percentage of neutrophils in older asthma subjects. No age-related differences were found for in vitro leukotriene production. However, LTB4 was significantly decreased in the airway of older adults with asthma and there was a strong tendency of lower levels of cysLT. In addition, there was an age-related decrease in GM-CSF production in peripheral blood mononuclear cells (PBMCs), which may account for the diminished production of leukotrienes in the airway of older asthmatics. Conclusion: This pilot study revealed age-related changes in sputum leukotriene levels. This demonstrates a key difference in the airway inflammatory state in older asthmatics, which may have therapeutic relevance regarding response to asthma treatments. http://www.immunityageing.com/content/7/1/8 Sharmilee Nyenhuis Elizabeth Schwantes Sameer Mathur Immunity & Ageing 2010, 7:8 2010-07-05T00:00:00Z doi:10.1186/1742-4933-7-8 Immunity & Ageing 1742-4933 7 8 2010-07-05T00:00:00Z XML The increasing ratio of ageing population poses new challenges to healthcare systems. The elderly frequently suffer from severe infections. Vaccination could protect them against several infectious diseases, but it can be effective only if cells that are capable of responding are still present in the repertoire. Recent vaccination strategies in the elderly might achieve low effectiveness due to age-related immune impairment. Immunosenescence affects both the innate and adaptive immunity.Beside individual variations of genetic predisposition, epigenetic changes over the full course of human life exert immunomodulating effects. Disturbances in macrophage-derived cytokine release and reduction of the natural killer cell mediated cytotoxicity lead to increased frequency of infections. Ageing dampens the ability of B cells to produce antibodies against novel antigens. Exhausted memory B lymphocyte subsets replace naïve cells. Decline of cell-mediated immunity is the consequence of multiple changes, including thymic atrophy, reduced output of new T lymphocytes, accumulation of anergic memory cells, and deficiencies in cytokines production. Persistent viral and parasitic infections contribute to the loss of immunosurveillance and premature exhaustion of T cells. Reduced telomerase activity and Toll-like receptor expression can be improved by chemotherapy. Reversion of thymic atrophy could be achieved by thymus transplantation, depletion of accumulated dysfunctional naive T cells and herpesvirus-specific exhausted memory cells. Administration of interleukin (IL)-2, IL-7, IL-10, keratinocyte growth factor, thymic stromal lymphopoietin, as well as leptin and growth hormone boost thymopoiesis. In animals, several strategies have been explored to produce superior vaccines. Among them, virosomal vaccines containing polypeptide antigens or DNA plasmids as well as new adjuvanted vaccine formulations elicit higher dendritic cell activity and more effective serologic than conventional vaccines responses in the elderly. Hopefully, at least some of these approaches can be translated to human medicine in a not too far future. http://www.immunityageing.com/content/7/1/7 Joseph Ongradi Valeria Kovesdi Immunity & Ageing 2010, 7:7 2010-06-14T00:00:00Z doi:10.1186/1742-4933-7-7 Immunity & Ageing 1742-4933 7 7 2010-06-14T00:00:00Z XML Nonagenarians are the fastest growing sector of populations across Western European and the developed world. They are some of the oldest members of our societies and survivors of their generation and may help us understand how to age not only longer, but better.The Belfast Longevity Group enlisted the help of 500 community-living, mobile, mentally competent, 'elite' nonagenarians, as part of an ongoing study of ageing. We assessed some immunological, cardiovascular, nutritional and genetic factors and some aspects of their interaction in this group of 'oldest old'.Here we present some of the evidence related to genetic and nutritional factors which seem to be important for good quality ageing in nonagenarians from the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST). http://www.immunityageing.com/content/7/1/6 I Maeve Rea Immunity & Ageing 2010, 7:6 2010-05-27T00:00:00Z doi:10.1186/1742-4933-7-6 Immunity & Ageing 1742-4933 7 6 2010-05-27T00:00:00Z XML Alpha integrins play an important role in cell to cell and cell to extra-cellular matrix interactions required for an effective T-lymphocyte-mediated immune response, however little is known about age related differences in expression of alpha integrins on T-cells in humans. We here measured alpha-4 (α4) integrin (CD49d) expression on T-lymphocytes via peripheral blood sampling, comparing parameters between cohorts of young and old adults. No age-related differences were found for the absolute numbers of T-cells, although the percentage of CD4+ T-cells in older adults was significantly greater and the percentage of CD8+ T-cells lower than in younger cohorts. Percentage and absolute numbers of CD3+ T-cells co-expressing CD49d were significantly lower in older adults compared to younger cohorts, and the percentage of gated CD4+ and CD8+ cells that co-labelled positively for CD49d was also reduced in this group. There were no age-related differences in circulating levels of cytokines (Type I interferons) that are known to regulate cell surface integrin expression. Reduced expression of alpha integrins on T-cells may be an early indicator of the loss of homeostatic control that occurs with ageing, contributing to diminished effector T-cell responses during senescence. http://www.immunityageing.com/content/7/1/5 Christine Crooks Martin Cross Clare Wall Immunity & Ageing 2010, 7:5 2010-04-26T00:00:00Z doi:10.1186/1742-4933-7-5 Immunity & Ageing 1742-4933 7 5 2010-04-26T00:00:00Z XML Background: There is reported to be a decline in immune function and an alteration in the frequency of circulating lymphocytes with advancing age. There are also differences in ageing and lifespan between males and females. We performed this study to see if there were differences between males and females in the frequency of the different lymphocyte subsets with age. Results: Using flow cytometry we have examined different populations of peripheral blood leukocytes purified from healthy subjects with age ranging from the third to the tenth decade. We used linear regression analysis to determine if there is a linear relationship between age and cell frequencies. For the whole group, we find that with age there is a significant decline in the percentage of naïve T cells and CD8+ T cells, and an increase in the percentage of effector memory cells, CD4+foxp3+ T cells and NK cells. For all cells where there was an effect of ageing, the slope of the curve was greater for men than for women and this was statistically significant for CD8+αβ+ T cells and CD3+CD45RA-CCR7- effector memory cells. There was also a difference for naïve cells but this was not significant. Conclusion: The cause of the change in percentage of lymphocyte subsets with age, and the different effects on males and females is not fully understood but warrants further study. http://www.immunityageing.com/content/7/1/4 Jun Yan Judith Greer Renee Hull John O Sullivan Robert Henderson Stephen Read Pamela McCombe Immunity & Ageing 2010, 7:4 2010-03-16T00:00:00Z doi:10.1186/1742-4933-7-4 Immunity & Ageing 1742-4933 7 4 2010-03-16T00:00:00Z XML Background: Oncogenic γ-herpesviruses establish life-long infections in their hosts and control of these latent infections is dependent on continual immune surveillance. Immune function declines with age, raising the possibility that immune control of γ-herpesvirus infection becomes compromised with increasing age, allowing viral reactivation and/or increased latent load, both of which are associated with the development of malignancies. Results: In this study, we use the experimental mouse γ-herpesvirus model, γHV68, to investigate viral immunity in aged mice. We found no evidence of viral recrudescence or increased latent load in aged latently-infected mice, suggesting that effective immune control of γ-herpesvirus infection remains intact with ageing. As both cellular and humoral immunity have been implicated in host control of γHV68 latency, we independently examined the impact of ageing on γHV68-specific CD8 T cell function and antibody responses. Virus-specific CD8 T cell numbers and cytolytic function were not profoundly diminished with age. In contrast, whereas ELISA titers of virus-specific IgG were maintained over time, there was a progressive decline in neutralizing activity. In addition, although aged mice were able to control de novo acute infection with only slightly delayed viral clearance, serum titers of neutralizing antibody were reduced in aged mice as compared to young mice. Conclusion: Although there is no obvious loss of immune control of latent virus, these data indicate that ageing has differential impacts on anti-viral cellular and humoral immune protection during persistent γHV68 infection. This observation has potential relevance for understanding γ-herpesvirus immune control during disease-associated or therapeutic immunosuppression. http://www.immunityageing.com/content/7/1/3 Eric Yager In-Jeong Kim Michael Freeman Kathleen Lanzer Claire Burkum Tres Cookenham David Woodland Marcia Blackman Immunity & Ageing 2010, 7:3 2010-02-02T00:00:00Z doi:10.1186/1742-4933-7-3 Immunity & Ageing 1742-4933 7 3 2010-02-02T00:00:00Z XML Background: The prevalence of coronary artery diseases is low among Down Syndrome (DS) patients and they rarely die of atherosclerotic complications. Histopathological investigations showed no increase in atherosclerosis, or even a total lack of atherosclerotic changes, in DSAimThe aim of our study is to investigate the relationship between age and brain-derived neurotrophic factor (BDNF) levels in Down Syndrome (DS).Subjects and methodsThree groups of DS patients were studied: the first consisted of 23 children (age 2-14 years); the second of 14 adults (age 20-50 years), the third group of 13 elderly persons (>60 years) and a controls group of 20 healthy patients (age 15-60 years).The analytes of interest were quantified using a biochip array analyzer (Evidence®, Randox Ltd., Crumlin, UK). Results: Plasma BDNF was higher in DS patients than in controls and there was a significant age-related increase. Serum levels of IL-6 and MCP-1 were also higher in DS children and adults, but not in older patients, than in healthy control. High levels of circulating BDNF may protect DS patients from the clinical complications of atherosclerosis. However, the striking drop in peripheral BDNF levels with age might predispose these patients to clinical manifestations of dementia in later life. http://www.immunityageing.com/content/7/1/2 Giada Dogliotti Emanuela Galliera Federico Licastro Massimiliano Corsi Immunity & Ageing 2010, 7:2 2010-01-25T00:00:00Z doi:10.1186/1742-4933-7-2 Immunity & Ageing 1742-4933 7 2 2010-01-25T00:00:00Z XML A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy between April 7 and 8th 2009. Here the lecture by Sikora with some input from the chairpersons Scapagnini and Barbagallo is summarized. Ageing is manifested by the decreasing health status and increasing probability to acquire age-related disease such as cancer, Alzheimer's disease, atherosclerosis, metabolic disorders and others. They are likely caused by low grade inflammation driven by oxygen stress and manifested by the increased level of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α, encoded by genes activated by the transcription factor NF-κB. It is believed that ageing is plastic and can be slowed down by caloric restriction as well as by some nutraceuticals. Accordingly, slowing down ageing and postponing the onset of age-related diseases might be achieved by blocking the NF-κB-dependent inflammation. In this review we consider the possibility of the spice curcumin, a powerful antioxidant and anti-inflammatory agent possibly capable of improving the health status of the elderly. http://www.immunityageing.com/content/7/1/1 Ewa Sikora Giovanni Scapagnini Mario Barbagallo Immunity & Ageing 2010, 7:1 2010-01-17T00:00:00Z doi:10.1186/1742-4933-7-1 Immunity & Ageing 1742-4933 7 1 2010-01-17T00:00:00Z XML The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria remain unclear.Conventional definitions identify the patients too late, miss subjects with cognitive impairment short of dementia, and emphasize consequences rather than causes, the true bases for treatment and prevention. We should throw out current diagnostic categories and describe cognitive impairment clinically and according to commonly agreed instruments that document the demographic data in a standardized manner and undertake a systematic effort to identify the underlying aetiology in each case.Increased effort should be targeted towards the concept of and criteria for Vascular Cognitive Impairment and Post-Stroke Dementia as well as for genetic factors involved, especially as these categories hold promise for early prevention and treatment. http://www.immunityageing.com/content/6/1/13 Francesco Iemolo Giovanni Duro Claudia Rizzo Laura Castiglia Vladimir Hachinski Calogero Caruso Immunity & Ageing 2009, 6:13 2009-11-06T00:00:00Z doi:10.1186/1742-4933-6-13 Immunity & Ageing 1742-4933 6 13 2009-11-06T00:00:00Z XML A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy on 7-8 April 2009. Three lectures from that Symposium by G. Campisi, L. Ginaldi and F. Licastro are here summarized. Ageing is a complex process which negatively impacts on the development of various bodily systems and its ability to function. A long life in a healthy, vigorous, youthful body has always been one of humanity's greatest dreams. Thus, a better understanding of the pathophysiology of age-related diseases is urgently required to improve our understanding of maintaining good health in the elderly and to program possible therapeutic intervention. http://www.immunityageing.com/content/6/1/12 Giuseppina Campisi Martina Chiappelli Massimo De Martinis Vito Franco Lia Ginaldi Rosario Guiglia Federico Licastro Domenico Lio Immunity & Ageing 2009, 6:12 2009-09-08T00:00:00Z doi:10.1186/1742-4933-6-12 Immunity & Ageing 1742-4933 6 12 2009-09-08T00:00:00Z XML