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Immunology of Aging

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 April 2017) | Viewed by 58278

Special Issue Editor

Department of Physiology, Faculty of Biology, Complutense University of Madrid, 28040 Madrid, Spain
Interests: aging; imunosenescence; oxidation–inflammation; oxi-inflamm-aging
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Aging is accompanied by an impairment of the physiological systems, including the immune system. The age-related changes of immune functions, which are denominated immunosenescence, are the cause of the increased vulnerability to infections, cancer, and inflammatory diseases with age. The adequate function of immune cells has been proposed as a marker of health, rate of aging or biological age, as well as a predictor of longevity. One of the most important molecular causes of immunosenescence is the alteration in the regulation of signaling pathways. In agreement with the oxidation theory of aging, and considering the age-related inflammation and the relation between oxidation and inflammation, it has been proposed that the immune cells show an increase of oxidant and inflammatory compounds and a decrease of antioxidant and anti-inflammatory defenses. These chronic oxidative and inflammatory stresses are involved in immunosenscence and also in oxi-inflamm-aging of the organism, and consequently in the rate of aging. Thus, in several states associated with oxidation and inflammation such as anxiety, depression, inadequate stress response, obesity, cognitive deterioration or neurodegenerative diseases, among others, there is premature immunosenescence and mortality. The confirmation of the role of the immune system in the rate of aging is that several life style strategies, such as the type of diet, physical activity, environmental enrichment, social relationships, etc., can improve the immune redox and inflammatory state and thus increase the longevity of the subjects.
This Special Issue is devoted to the age-related increase in inflammatory and oxidative stress states of the immune system, the deregulation of the signaling pathways, and how these are involved in oxi-inflamm-aging and consequently in the rate of aging, morbidity and the lifespan of each individual. Moreover, the effectiveness of several strategies of life style in slowing down the aging process, through the modulation of immunosenescence, will be commented on.

Prof. Dr. Monica De la Fuente
Guest Editor

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Keywords

  • Aging
  • Immunosenescence
  • Oxi-inflamm-aging
  • Antioxidant defenses
  • Oxidant compounds
  • Inflammatory compounds
  • Models of premature aging
  • Signal pathways

Related Special Issue

Published Papers (8 papers)

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Research

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3302 KiB  
Article
An Appropriate Modulation of Lymphoproliferative Response and Cytokine Release as Possible Contributors to Longevity
by Irene Martínez de Toda, Carmen Vida and Mónica De la Fuente
Int. J. Mol. Sci. 2017, 18(7), 1598; https://doi.org/10.3390/ijms18071598 - 24 Jul 2017
Cited by 14 | Viewed by 4559
Abstract
The decrease in the proliferative response of lymphocytes is one of the most evident among the age-related changes of the immune system. This has been linked to a higher risk of mortality in both humans and experimental animals. However, long-lived individuals, in spite [...] Read more.
The decrease in the proliferative response of lymphocytes is one of the most evident among the age-related changes of the immune system. This has been linked to a higher risk of mortality in both humans and experimental animals. However, long-lived individuals, in spite of optimally maintaining most of the functions of the immune system, also seem to show an impaired proliferative response. Thus, it was hypothesized that these individuals may have distinct evolution times in this proliferation and a different modulatory capacity through their cytokine release profiles. An individualized longitudinal study was performed on female ICR-CD1 mice, starting at the adult age (40 weeks old), analyzing the proliferation of peritoneal leukocytes at different ages in both basal conditions and in the presence of the mitogen Concanavalin A, for 4, 24 and 48 h of culture. The cytokine secretions (IL-2, IL-17, IL-1β, IL-6, TNF-α and IL-10) in the same cultures were also studied. Long-lived mice show a high proliferative capacity after short incubation times and, despite experiencing a functional decline when they are old, are able to compensate this decrease with an appropriate modulation of the lymphoproliferative response and cytokine release. This could explain their elevated resistance to infections and high longevity. Full article
(This article belongs to the Special Issue Immunology of Aging)
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8153 KiB  
Article
Effect of Cytomegalovirus (CMV) and Ageing on T-Bet and Eomes Expression on T-Cell Subsets
by Fakhri Hassouneh, Nelson Lopez-Sejas, Carmen Campos, Beatriz Sanchez-Correa, Raquel Tarazona, Alejandra Pera and Rafael Solana
Int. J. Mol. Sci. 2017, 18(7), 1391; https://doi.org/10.3390/ijms18071391 - 29 Jun 2017
Cited by 9 | Viewed by 5600
Abstract
The differential impact of ageing and cytomegalovirus (CMV) latent infection on human T-cell subsets remains to some extent controversial. The purpose of this study was to analyse the expression of the transcription factors T-bet and Eomes and CD57 on CD4+, CD4hiCD8 [...] Read more.
The differential impact of ageing and cytomegalovirus (CMV) latent infection on human T-cell subsets remains to some extent controversial. The purpose of this study was to analyse the expression of the transcription factors T-bet and Eomes and CD57 on CD4+, CD4hiCD8lo and CD8+ T-cell subsets in healthy individuals, stratified by age and CMV serostatus. The percentage of CD4+ T-cells expressing T-bet or Eomes was very low, in particular in CD4+ T-cells from young CMV-seronegative individuals, and were higher in CMV-seropositive older individuals, in both CD57− and CD57+ CD4+ T-cells. The study of the minor peripheral blood double-positive CD4hiCD8lo T-cells showed that the percentage of these T-cells expressing both Eomes and T-bet was higher compared to CD4+ T-cells. The percentage of CD4hiCD8lo T-cells expressing T-bet was also associated with CMV seropositivity and the coexpression of Eomes, T-bet and CD57 on CD4hiCD8lo T-cells was only observed in CMV-seropositive donors, supporting the hypothesis that these cells are mature effector memory cells. The percentage of T-cells expressing Eomes and T-bet was higher in CD8+ T-cells than in CD4+ T-cells. The percentages of CD8+ T-cells expressing Eomes and T-bet increased with age in CMV-seronegative and -seropositive individuals and the percentages of CD57− CD8+ and CD57+ CD8+ T-cells coexpressing both transcription factors were similar in the different groups studied. These results support that CMV chronic infection and/or ageing are associated to the expansion of highly differentiated CD4+, CD4hiCD8lo and CD8+ T-cells that differentially express T-bet and Eomes suggesting that the expression of these transcription factors is essential for the generation and development of an effector-memory and effector T lymphocytes involved in conferring protection against chronic CMV infection. Full article
(This article belongs to the Special Issue Immunology of Aging)
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Review

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1152 KiB  
Review
Markers of T Cell Senescence in Humans
by Weili Xu and Anis Larbi
Int. J. Mol. Sci. 2017, 18(8), 1742; https://doi.org/10.3390/ijms18081742 - 10 Aug 2017
Cited by 141 | Viewed by 13103
Abstract
Many countries are facing the aging of their population, and many more will face a similar obstacle in the near future, which could be a burden to many healthcare systems. Increased susceptibility to infections, cardiovascular and neurodegenerative disease, cancer as well as reduced [...] Read more.
Many countries are facing the aging of their population, and many more will face a similar obstacle in the near future, which could be a burden to many healthcare systems. Increased susceptibility to infections, cardiovascular and neurodegenerative disease, cancer as well as reduced efficacy of vaccination are important matters for researchers in the field of aging. As older adults show higher prevalence for a variety of diseases, this also implies higher risk of complications, including nosocomial infections, slower recovery and sequels that may reduce the autonomy and overall quality of life of older adults. The age-related effects on the immune system termed as “immunosenescence” can be exemplified by the reported hypo-responsiveness to influenza vaccination of the elderly. T cells, which belong to the adaptive arm of the immune system, have been extensively studied and the knowledge gathered enables a better understanding of how the immune system may be affected after acute/chronic infections and how this matters in the long run. In this review, we will focus on T cells and discuss the surface and molecular markers that are associated with T cell senescence. We will also look at the implications that senescent T cells could have on human health and diseases. Finally, we will discuss the benefits of having these markers for investigators and the future work that is needed to advance the field of T cell senescence markers. Full article
(This article belongs to the Special Issue Immunology of Aging)
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635 KiB  
Review
Role of Hormones in the Regulation of RACK1 Expression as a Signaling Checkpoint in Immunosenescence
by Marco Racchi, Erica Buoso, Melania Ronfani, Melania M. Serafini, Marilisa Galasso, Cristina Lanni and Emanuela Corsini
Int. J. Mol. Sci. 2017, 18(7), 1453; https://doi.org/10.3390/ijms18071453 - 06 Jul 2017
Cited by 19 | Viewed by 6013
Abstract
Immunosenescence defines the decline in immune function that occurs with aging. This has been associated, at least in part, with defective cellular signaling via protein kinase C (PKC) signal transduction pathways. Our data suggest reduced PKC activation and consequently reduced response to lipopolysaccharide [...] Read more.
Immunosenescence defines the decline in immune function that occurs with aging. This has been associated, at least in part, with defective cellular signaling via protein kinase C (PKC) signal transduction pathways. Our data suggest reduced PKC activation and consequently reduced response to lipopolysaccharide (LPS) stimulation and cytokine release. The lack of PKC activation seems to be dependent on the reduced expression of the receptor for activated C kinase 1 (RACK1), a scaffolding protein involved in multiple signal transduction cascades. The defective expression of RACK1 may be dependent on age-related alteration of the balance between the adrenal hormones cortisol and dehydroepiandrosterone (DHEA). DHEA levels reduce with aging, while cortisol levels remain substantially unchanged, resulting in an overall increase in the cortisol:DHEA ratio. These hormonal changes are significant in the context of RACK1 expression and signaling function because DHEA administration in vivo and in vitro can restore the levels of RACK1 and the function of the PKC signaling cascade in aged animals and in human cells. In contrast, there is evidence that cortisol can act as a negative transcriptional regulator of RACK1 expression. The rack1 gene promoter contains a glucocorticoid responsive element that is also involved in androgen signaling. Furthermore DHEA may have an indirect influence on the post-transcriptional regulation of the functions of the glucocorticoid receptor. In this review, we will examine the role of the hormonal regulation of rack1 gene transcriptional regulation and the consequences on signaling and function in immune cells and immunosenescence. Full article
(This article belongs to the Special Issue Immunology of Aging)
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208 KiB  
Review
Age-Related Changes in Immunological and Physiological Responses Following Pulmonary Challenge
by Edmund J. Miller and Helena M. Linge
Int. J. Mol. Sci. 2017, 18(6), 1294; https://doi.org/10.3390/ijms18061294 - 17 Jun 2017
Cited by 18 | Viewed by 4379
Abstract
This review examines the current status of knowledge of sepsis and pneumonia in the elderly population and how the dynamics of the pulmonary challenge affects outcome and consequences. Led by an unprecedented shift in demographics, where a larger proportion of the population will [...] Read more.
This review examines the current status of knowledge of sepsis and pneumonia in the elderly population and how the dynamics of the pulmonary challenge affects outcome and consequences. Led by an unprecedented shift in demographics, where a larger proportion of the population will reach an older age, clinical and experimental research shows that aging is associated with certain pulmonary changes, but it is during infectious insult of the lungs, as in the case of pneumonia, that the age-related differences in responsiveness and endurance become obvious and lead to a worse outcome than in the younger population. This review points to the neutrophil, and the endothelium as important players in understanding age-associated changes in responsiveness to infectious challenge of the lung. It also addresses how the immunological set-point influences injury-repair phases, remote organ damage and how intake of drugs may alter the state of responsiveness in the users. Further, it points out the importance of considering age as a factor in inclusion criteria in clinical trials, in vitro/ex vivo experimental designs and overall interpretation of results. Full article
(This article belongs to the Special Issue Immunology of Aging)
925 KiB  
Review
Dendritic Cell-Airway Epithelial Cell Cross-Talk Changes with Age and Contributes to Chronic Lung Inflammatory Diseases in the Elderly
by Anshu Agrawal
Int. J. Mol. Sci. 2017, 18(6), 1206; https://doi.org/10.3390/ijms18061206 - 06 Jun 2017
Cited by 17 | Viewed by 5813
Abstract
Age-associated dysregulated immune and inflammatory responses are one of the major factors responsible for the prevalence of chronic respiratory diseases in the older population. Pulmonary dendritic cells (DCs) are present below the airway epithelial cells (AECs) and are critical in initiating effective immune [...] Read more.
Age-associated dysregulated immune and inflammatory responses are one of the major factors responsible for the prevalence of chronic respiratory diseases in the older population. Pulmonary dendritic cells (DCs) are present below the airway epithelial cells (AECs) and are critical in initiating effective immune responses to harmful pathogens while maintaining tolerance against harmless antigens. The interaction between DCs and AECs plays a crucial role in lung immunity at homeostasis and during infections. The functions of both DCs and AECs are impacted with age. The present report reviews how the potential crosstalk between pulmonary DCs and AECs is dysregulated in the elderly impairing the capacity to maintain tolerance at the respiratory surfaces, which results in severe and chronic respiratory inflammatory diseases. We also discuss how such DC-AECs crosstalk will provide insight into the mechanisms underlying the increased susceptibility of the elderly to pulmonary inflammatory diseases. Full article
(This article belongs to the Special Issue Immunology of Aging)
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215 KiB  
Review
Aged Lymphatic Vessels and Mast Cells in Perilymphatic Tissues
by Sarit Pal, Cynthia J. Meininger and Anatoliy A. Gashev
Int. J. Mol. Sci. 2017, 18(5), 965; https://doi.org/10.3390/ijms18050965 - 03 May 2017
Cited by 15 | Viewed by 4563
Abstract
This review provides a comprehensive summary of research on aging-associated alterations in lymphatic vessels and mast cells in perilymphatic tissues. Aging alters structure (by increasing the size of zones with low muscle cell investiture), ultrastructure (through loss of the glycocalyx), and proteome composition [...] Read more.
This review provides a comprehensive summary of research on aging-associated alterations in lymphatic vessels and mast cells in perilymphatic tissues. Aging alters structure (by increasing the size of zones with low muscle cell investiture), ultrastructure (through loss of the glycocalyx), and proteome composition with a concomitant increase in permeability of aged lymphatic vessels. The contractile function of aged lymphatic vessels is depleted with the abolished role of nitric oxide and an increased role of lymphatic-born histamine in flow-dependent regulation of lymphatic phasic contractions and tone. In addition, aging induces oxidative stress in lymphatic vessels and facilitates the spread of pathogens from these vessels into perilymphatic tissues. Aging causes the basal activation of perilymphatic mast cells, which, in turn, restricts recruitment/activation of immune cells in perilymphatic tissues. This aging-associated basal activation of mast cells limits proper functioning of the mast cell/histamine/NF-κB axis that is essential for the regulation of lymphatic vessel transport and barrier functions as well as for both the interaction and trafficking of immune cells near and within lymphatic collecting vessels. Cumulatively, these changes play important roles in the pathogenesis of alterations in inflammation and immunity associated with aging. Full article
(This article belongs to the Special Issue Immunology of Aging)
1588 KiB  
Review
Fueling Inflamm-Aging through Mitochondrial Dysfunction: Mechanisms and Molecular Targets
by Anna Picca, Angela Maria Serena Lezza, Christiaan Leeuwenburgh, Vito Pesce, Riccardo Calvani, Francesco Landi, Roberto Bernabei and Emanuele Marzetti
Int. J. Mol. Sci. 2017, 18(5), 933; https://doi.org/10.3390/ijms18050933 - 28 Apr 2017
Cited by 119 | Viewed by 13379
Abstract
Among the complex determinants of aging, mitochondrial dysfunction has been in the spotlight for a long time. As the hub for many cellular functions, the maintenance of an adequate pool of functional mitochondria is crucial for tissue homeostasis. Their unique role in energy [...] Read more.
Among the complex determinants of aging, mitochondrial dysfunction has been in the spotlight for a long time. As the hub for many cellular functions, the maintenance of an adequate pool of functional mitochondria is crucial for tissue homeostasis. Their unique role in energy supply makes these organelles essential, especially in those tissues strictly dependent on oxidative metabolism. Mitochondrial quality control (MQC) is ensured by pathways related to protein folding and degradation as well as by processes involving the entire organelle, such as biogenesis, dynamics, and mitophagy. Dysfunctional MQC, oxidative stress and inflammation are hallmarks of senescence and chronic degenerative diseases. One of the consequences of age-related failing MQC and oxidative stress is the release of mitochondria-derived damage-associated molecular patterns (DAMPs). Through their bacterial ancestry, these molecules contribute to mounting an inflammatory response by interacting with receptors similar to those involved in pathogen-associated responses. Mitochondrial DAMPs, especially cell-free mitochondrial DNA, have recently become the subject of intensive research because of their possible involvement in conditions associated with inflammation, such as aging and degenerative diseases. Here, we review the contribution of mitochondrial DAMPs to inflammation and discuss some of the mechanisms at the basis of their generation. Full article
(This article belongs to the Special Issue Immunology of Aging)
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