Morbidity and mortality due to infectious disease is greater in the elderly than in the young, at least partly because of age-associated decreased immune competence, which renders individuals more susceptible to pathogens. This susceptibility is particularly evident for novel infectious agents such as in severe acute respiratory syndrome but is ...

Both mouse and human exhibit deficiencies in humoral immunity during 'old age'. While alterations in phenotype and function have been well documented, the molecular mechanisms that result in immune senescence remain undefined. B lymphopoiesis is suppressed in senescent mice, which may result from deficits at the pre-B-cell stage or earlier ...

Aged animals and humans exhibit a decreased T-cell activation response although they also exhibit increased susceptibility to responses to self-antigens and a loss of self-tolerance. The age-related alteration in T-cell reactivity, polyclonal expansion of T cells, and enhanced production of autoantibodies may reflect the numerous age-associated alterations in the T-cell ...

Advanced glycation end products (AGEs), S100/calgranulins, and HMGB1 proteins supposedly play a pivotal role in diabetes mellitus and other chronic inflammatory diseases by promoting cellular dysfunction via binding to cellular surface receptors. Particularly, engagement of the receptor for AGEs (RAGE) has gained major attention because it converts short-lasting cellular activation ...

The strict limit in proliferative potential of normal human somatic cells - a process known as replicative senescence - is highly relevant to the immune system, because clonal expansion is fundamental to adaptive immunity. CD8(+) T cells that undergo extensive rounds of antigen-driven proliferation in cell culture invariably reach the ...

The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses ...

Naturally occurring CD4(+)CD25(+) regulatory T (T(R)) cells, a component of the innate immune response, which play a key role in the maintenance of self-tolerance, have become the focus of numerous studies over the last decade. These cells inhibit the immune response in an Ag-nonspecific manner, interacting with other T cells. ...

Vitamin D is a steroid hormone that, in addition to its well-characterized role in calcium/phosphate metabolism, has been found to have regulatory properties for immune system function. The nuclear vitamin D receptor is widely expressed in tissues, but has also been shown to be regulated by hormones, growth factors, and ...

For lymphocytes, the ability to undergo clonal expansion is crucial for effective immune function. Telomerase activity compensates for telomere erosion during cell division and contributes to the capability of lymphocytes to maintain cellular proliferation. In addition, telomerase activity may have a fundamental role in cell growth and survival. To determine ...

Immunosenescence is the consequence of the continuous attrition caused by chronic antigenic stress. The most important characteristics of immunosenescence (accumulation of memory and effector T cells, reduction of naive T cells, shrinkage of T cell repertoire, reduction of the immunological space) are compatible with this assumption. Immunosenescence can be taken ...

Sixteen native ram lambs weaned at 10 wk of age were divided into two groups. Eight animals were immunized against LHRH with a mixture of two fusion proteins: ovalbumin-LHRH-7 and thioredoxin-LHRH-7. The immunized lambs received a primary immunization plus two booster immunizations at 4 and 12 wks. Animals in the ...

The immune system exhibits profound age-related changes, collectively termed immunosenescence. The most visible of these is the decline in protective immunity, which results from a complex interaction of primary immune defects and compensatory homeostatic mechanisms. The sum of these changes is a dysregulation of many processes that normally ensure optimal ...

BACKGROUND: The hypothesis that common infections can modulate the onset and course of tic disorders and early-onset obsessive-compulsive disorder (OCD) in pediatric populations is longstanding. To date, most investigations have focused on the hypothesis of molecular mimicry and humoral immune responses. This study was carried out to investigate whether cytokines ...

Epidemiological studies have suggested an association between vitamin C (and other antioxidant vitamins) and cancer risk. However, the mechanisms accounting for prevention have not been extensively investigated. In skin, vitamin C (ascorbic acid) exerts different biological roles, including photoprotective effects and participation in collagen synthesis. This paper reports new findings ...

We demonstrate herein that zinc pyrithione can induce apoptosis at nanomolar concentrations. Zinc pyrithione was a potent inducer of cell death causing greater than 40-60% apoptosis among murine thymocytes, murine splenic lymphocytes and human Ramos B and human Jurkat T cells. Conversely, the addition of a zinc chelator protected thymocytes ...

With advancing age, the immune system undergoes changes that predispose to autoimmune reactivity. Aging reduces the efficiency of physical barriers, decreasing protection against invasive pathogens, and exposing previously hidden antigens in the body's own tissues. Self-antigens acquire alterations that increase their immunogenicity. In addition, the ability of innate immunity to ...

Phosphatidylserine (PS) on apoptotic cells promotes their uptake and induces anti-inflammatory responses in phagocytes, including TGF-beta release. Little is known regarding the effects of PS on adaptive immune responses. We therefore investigated the effects of PS-containing liposomes on immune responses in mice in vivo. PS liposomes specifically inhibited responses to ...

The vitamin K-dependent gamma-carboxylation system in the endoplasmic reticulum membrane responsible for gamma-carboxyglutamic acid modification of vitamin K-dependent proteins includes gamma-carboxylase and vitamin K 2,3-epoxide reductase (VKOR). An understanding of the mechanism by which this system works at the molecular level has been hampered by the difficulty of identifying VKOR ...

The function of the immune system is to maintain body integrity by defending against infections, cancers, autoimmune diseases and inflammation-related chronic diseases. The immune response is known to become defective with aging, leading to decreased longevity and appearance of age-related disease. The most important changes occur in T-cell immunity, and ...

Many polysaccharides obtained from natural sources are considered to be biological response modifiers and have been shown to enhance various immune responses. Here, we investigated the immunomodulating effects of arabinogalactan (AG) and fucoidan (FU) in vitro. Mouse spleen lymphocytes became cytotoxic to tumor cells after culture with AG and FU ...

The kidneys exhibit age-associated deterioration in function via a loss of 20% to 25% kidney mass, particularly from the renal cortex and increased fibrosis. Oxidative stress has been found to mediate age-associated renal cell injury and cell death, particularly apoptosis. Oxidative stress results from an imbalance between the levels of ...

Neutrophils are the first barrier against infections. Aged neutrophils display impaired oxidative burst and phagocytosis with subsequent less capability to destroy bacteria. In successful ageing (nonagenarians), neutrophil efficiency (phagocytosis) increases. After ingested microbes, aged neutrophils are less prone to undergo apoptosis favouring chronic inflammation. Moreover, the superoxide dismutase (SOD) activity, ...

Aging is characterized by a proinflammatory state that contributes to the onset of disability and age-related diseases. Proinflammatory cytokines play a central role in mediating cellular and physiological responses. The levels of these cytokines may reflect immune system effectiveness. Studies of the effects of aging on inflammatory response show interleukin-6 ...

Two siblings with severe combined immune deficiency, one with maternal engraftment and detectable immunologic functions who was alive at the age of 8 years are presented. Both patients had the same JAK3 gene mutation, suggesting that maternal engraftment may result in immune competence leading to long-term survival in patients with ...

Respiratory tract infections are a leading cause of morbidity and mortality in the elderly. Many factors, such as malnutrition and the presence of structural lung disease, increase the risk of respiratory infection in older individuals. Aging is also accompanied by a gradual decline in many aspects of immune function, and ...

Aging can be characterized by structural changes and functional deterioration during the lifetime, for which hundreds of explanations have been put forward. Recently, we have proposed the gate theory of aging, in which gatekeeper molecules at the membrane level would play the prime role in determining the senescent phenotype. Caveolin-1 ...

Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. A decrease in functional competence of individual natural killer (NK) cells is found with advancing ...

Effective resetting of the immune system cannot be achieved by non-specific immunosuppression. Instead, novel strategies aim at harnessing the body's natural tolerance mechanisms to rectify an Ag-specific response without disturbing other immune functions. Fine-tuning of the balance between Ag-specific effector and regulatory T (Tr) cells is a promising strategy that ...

It is well documented that long term potentiation (LTP) is impaired in the hippocampus of the aged animal. Among the changes that contribute to this impairment is an increase in hippocampal concentration of the pro-inflammatory cytokine interleukin-1beta (IL-1beta), and increased IL-1beta-induced signaling. In this study we investigated the possibility that ...

Aging is associated with impairment of T cell function. We demonstrate here that age-associated declines in T cell signaling are due to the inability to form effective immune synapses at the site of the T cell receptor and antigen interaction. On the basis of our previous research with vitamin E ...

Immunization with the hen egg-white lysozyme (HEL) protein induces T cells to various of its peptide determinants. The distribution of such T cells, however, does not correlate with the peptide level of each epitope on class II molecules. For this reason, we sought information on the cells responsible for Ag ...

A beneficial effect of fish oil in reducing inflammatory and cardiovascular diseases has been suggested. This effect occurs in part through fish oil's inhibition of synthesis of pro-inflammatory cytokines. Epidemiologic studies have shown a link between increased intake of vitamin E in diet and reduced risk of cardiovascular disease. Since ...

It is well known that leukocyte composition, T cell phenotypes and immune function change in aged mice and humans. However, limited and conflicting results on the age-related immune changes in middle-aged mice were reported. Identification of the characteristics of allogeneic immune responses in aging mice may offer important information for ...

Both the incidence and severity of herpes zoster (HZ) or shingles increase markedly with increasing age in association with a decline in varicella zoster virus (VZV)-specific immunity. Considerable evidence shows that behavioral stressors, prevalent in older adults, correlate with impairments of cellular immunity. Moreover, the presence of depressive symptoms in ...

Although apoptosis has been shown in vivo to be involved in the aging process, in vitro studies of age-dependent apoptosis are limited. In this study, apoptosis was examined in normal human fibroblasts exposed to H(2)O(2) to induce premature senescence and in spontaneously senescent human fibroblasts. Although apoptosis was not observed ...

OBJECTIVE: To determine effects of vitamin A, zinc and iron deficiency in Indonesian infants on the ability to produce immunoregulatory cytokines. DESIGN, SETTING AND SUBJECTS: Immunological assessment was done in 59 infants participating in a cross-sectional nutritional survey in rural West Java, Indonesia. Production of T-helper cell type-1 (Th1, cell-mediated) ...

Glucose can react non-enzymatically with amino groups of, for example, proteins, to yield derivatives termed advanced glycation end products (AGE), which contribute to many chronic progressive diseases associated with microvascular complications. The study aimed to determine the effect of AGE-modified albumin on THP-1 cells and human monocyte-derived macrophages. Bovine serum ...

Aging and local chronic inflammation are established risk factors for epithelial tumorigenesis. These risk factors can act individually and/or synergistically to increase the incidence of age-related carcinomas. The basis for this co-stimulatory response has not yet been defined, nor have the feedback mechanisms that are responsible for this synergism. This ...

Aging is associated with an impaired capacity of the immune system to respond properly to danger signals, such as infection and cancer. Here, we provide evidence that an impaired innate immune response, as measured by a low production capacity of pro- and anti-inflammatory cytokines upon ex vivo standardized danger signalling ...

PURPOSE: To review current knowledge of key pathogenetic pathways in age-related macular disease (AMD). METHODS: Experimental evidence and clinical observations are reviewed. RESULTS: A number of common downstream pathophysiologic pathways appear to be relevant in AMD manifestations irrespective of primary heterogeneous etiologies. These include sequelae of oxidative damage, retinal pigment ...

The free-living soil nematode Caenorhabditis elegans is a versatile model for the study of the genetic regulation of aging and of host-pathogen interactions. Many genes affecting multiple processes, such as neuroendocrine signalling, nutritional sensing and mitochondrial functions, have been shown to play important roles in determining the lifespan of C. ...

Immunosenescence is defined as the state of dysregulated immune function that contributes to the increased susceptibility to infection, cancer and autoimmune diseases observed in old organisms, including humans. However, dysregulations in the immune functions are normally counterbalanced by continuous adaptation of the body to the deteriorations that occur over time. ...

It is well known that the immune response decreases during aging, leading to a higher susceptibility to infections, cancers and autoimmune disorders. Most widely studied have been alterations in the adaptive immune response. Recently, the role of the innate immune response as a first-line defence against bacterial invasion and as ...

Innate and adaptive immune functions decline with age, leading to increased susceptibility to infectious diseases and cancer, and reduced responses to preventive vaccination in the elderly population. Macrophages function as 'pathogen sensors' and play an important role in the initiation of inflammatory responses, elimination of pathogens, manipulation of the adaptive ...

Neurodegenerative conditions share common primary risk factors and mediators of disease progression. Because many degenerative disorders are age related, deteriorating immunity in aging patients might impose additional risk. Adaptive (T-cell-mediated) immunity is a defense mechanism that instructs microglia to fight off and clear away self-derived enemies. Such adaptive immunity can ...

Functional analyses of changes in the immune response indicate that aging is associated with a decline of adaptive immunity whereas innate immunity is ramped up. Gene expression studies also support age-dependent changes in immunity. Studies using a large panel of methodologies and multiple species show that some of the most ...

BACKGROUND: We studied the effects of advanced glycation end products (AGEs), which are known to accumulate in patients with diabetes, autoimmune diseases, or that smoke, on human trophoblasts. METHODS: First trimester human chorionic villi of 6-10 week gestation were obtained. Expression and localization of the receptor for AGEs (RAGE) was ...

Aging of the immune system, or immunosenescence, is a complex subject best defined as a decline in cell-mediated immunity, particularly with respect to T cell function. Paradoxically with the decline in immune function is an increase in autoantibody frequency. It has been postulated that the accumulation of anamnestic cells over ...

A major cause of aging is thought to result from the cumulative effects of cell loss over time. In yeast, caloric restriction (CR) delays aging by activating the Sir2 deacetylase. Here we show that expression of mammalian Sir2 (SIRT1) is induced in CR rats as well as in human cells ...

The capacity of the remodeling immune responses during stress (immune plasticity) is fundamental to reach successful aging. We herein report two pivotal models to demonstrate the relevance of the immune plasticity in aging and successful aging. One model is represented by the circadian rhythms of immune responses; the other one ...