International Journal of Molecular Sciences

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Open AccessEditorial

Where Could Research on Immunosenescence Lead?

by Mónica De la Fuente

Int. J. Mol. Sci. 2019, 20(23), 5906; https://doi.org/10.3390/ijms20235906 - 25 Nov 2019

Cited by 2 | Viewed by 3346

Abstract

In the special issue of the International Journal of Molecular Sciences (ISSN 1422-0067) entitled: Immunosenescence and related processes, eight relevant articles are presented [...] Full article

(This article belongs to the Special Issue Immunosenescence and Related Processes)

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Research

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21 pages, 3438 KiB

Open AccessArticle

The Modulatory Effect of Gender and Cytomegalovirus-Seropositivity on Circulating Inflammatory Factors and Cognitive Performance in Elderly Individuals

by Svetlana Di Benedetto, Marcel Gaetjen and Ludmila Müller

Int. J. Mol. Sci. 2019, 20(4), 990; https://doi.org/10.3390/ijms20040990 - 25 Feb 2019

Cited by 21 | Viewed by 5582

Abstract

Aging is characterized by a chronic increase in the systemic levels of inflammatory cytokines even in ostensibly healthy individuals. The drivers of age-related increase in systemic inflammation are unclear but one potential contributor may be a persistent infection with Cytomegalovirus (CMV). In this [...] Read more.

Aging is characterized by a chronic increase in the systemic levels of inflammatory cytokines even in ostensibly healthy individuals. The drivers of age-related increase in systemic inflammation are unclear but one potential contributor may be a persistent infection with Cytomegalovirus (CMV). In this study, we characterized the inflammatory status of 161 older participants recruited to undergo a six-month training intervention. We investigated the influence of gender and CMV-seropositivity on the main inflammatory and anti-inflammatory circulating biomarkers, such as cytokines, receptor antagonist, soluble receptor, immune cells, and relevant metabolic markers. We found that both gender and CMV-seropositivity modulate circulating peripheral biomarkers, and that CMV-infection modifies associations among the latter. Moreover, we observed an interaction between CMV-serostatus and gender associations with cognitive abilities: gender differences in fluid intelligence (Gf) and working memory (WM) were noted only in CMV-negative individuals. Finally, we found that in the CMV-seronegative participants Gf, episodic memory (EM), and WM correlated negatively with pro-inflammatory tumor necrosis factor (TNF); and EM correlated positively with anti-inflammatory interleukin (IL)-10. In CMV-seropositive individuals EM and Gf correlated negatively with pro-inflammatory IL-6, while EM, Gf, and WM correlated negatively with anti-inflammatory IL-1RA. We conclude that both CMV-serostatus and gender may modulate neuroimmune factors, cognitive performance and the relationship between the two domains and should therefore be considered in comparative and interventional studies with elderly people. Full article

(This article belongs to the Special Issue Immunosenescence and Related Processes)

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17 pages, 1061 KiB

Open AccessArticle

Lymphoproliferation Impairment and Oxidative Stress in Blood Cells from Early Parkinson’s Disease Patients

by Carmen Vida, Hikaru Kobayashi, Antonio Garrido, Irene Martínez de Toda, Eva Carro, José Antonio Molina and Mónica De la Fuente

Int. J. Mol. Sci. 2019, 20(3), 771; https://doi.org/10.3390/ijms20030771 - 12 Feb 2019

Cited by 31 | Viewed by 5071

Abstract

In Parkinson’s Disease (PD), the peripheral changes in the functional capacity and redox state of immune cells has been scarcely investigated, especially in the early PD stages. Aging is a risk factor for PD, and the age-related impairment of the immune system, based [...] Read more.

In Parkinson’s Disease (PD), the peripheral changes in the functional capacity and redox state of immune cells has been scarcely investigated, especially in the early PD stages. Aging is a risk factor for PD, and the age-related impairment of the immune system, based on a chronic-oxidative stress situation, is involved in the rate of aging. We analyzed several functions in isolated peripheral blood neutrophils and mononuclear cells from PD stage 2 patients, and compared the results to those in healthy elderly and adult controls. Several oxidative stress and damage parameters were studied in whole blood cells. The results showed an impairment of the lymphoproliferative response in stimulated conditions in the PD patients compared with age-matched controls, who also showed typical immunosenescence in comparison with adult individuals. Higher oxidative stress and damage were observed in whole blood cells from PD patients (lower glutathione peroxidase activity, and higher oxidized glutathione and malondialdehyde contents). Our results suggest an accelerated immunosenescence in PD stage 2, and that several of the parameters studied could be appropriate peripheral biomarkers in the early stages of PD. Full article

(This article belongs to the Special Issue Immunosenescence and Related Processes)

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23 pages, 3004 KiB

Open AccessArticle

Oxidative-Inflammatory Stress in Immune Cells from Adult Mice with Premature Aging

by Antonio Garrido, Julia Cruces, Noemí Ceprián, Elena Vara and Mónica de la Fuente

Int. J. Mol. Sci. 2019, 20(3), 769; https://doi.org/10.3390/ijms20030769 - 12 Feb 2019

Cited by 42 | Viewed by 5535

Abstract

Oxidative and inflammatory stresses are closely related processes, which contribute to age-associated impairments that affect the regulatory systems such as the immune system and its immunosenescence. Therefore, the aim of this work was to confirm whether an oxidative/inflammatory stress occurs in immune cells [...] Read more.

Oxidative and inflammatory stresses are closely related processes, which contribute to age-associated impairments that affect the regulatory systems such as the immune system and its immunosenescence. Therefore, the aim of this work was to confirm whether an oxidative/inflammatory stress occurs in immune cells from adult mice with premature aging, similar to that shown in leukocytes from chronologically old animals, and if this results in immunosenescence. Several oxidants/antioxidants and inflammatory/anti-inflammatory cytokines were analyzed in peritoneal leukocytes from adult female CD1 mice in two models of premature aging—(a) prematurely aging mice (PAM) and (b) mice with the deletion of a single allele (hemi-zygotic: HZ) of the tyrosine hydroxylase (th) gene (TH-HZ), together with cells from chronologically old animals. Several immune function parameters were also studied in peritoneal phagocytes and lymphocytes. The same oxidants and antioxidants were also analyzed in spleen and thymus leukocytes. The results showed that the immune cells of PAM and TH-HZ mice presented lower values of antioxidant defenses and higher values of oxidants/pro-inflammatory cytokines than cells from corresponding controls, and similar to those in cells from old animals. Moreover, premature immunosenescence in peritoneal leukocytes from both PAM and TH-HZ mice was also observed. In conclusion, adult PAM and TH-HZ mice showed oxidative stress in their immune cells, which would explain their immunosenescence. Full article

(This article belongs to the Special Issue Immunosenescence and Related Processes)

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12 pages, 926 KiB

Open AccessArticle

Comparison of the Effect of Melatonin Treatment before and after Brain Ischemic Injury in the Inflammatory and Apoptotic Response in Aged Rats

by Lisa Rancan, Sergio D. Paredes, Cruz García, Pablo González, Cruz Rodríguez-Bobada, Mario Calvo-Soto, Bryan Hyacinthe, Elena Vara and Jesús A. F. Tresguerres

Int. J. Mol. Sci. 2018, 19(7), 2097; https://doi.org/10.3390/ijms19072097 - 19 Jul 2018

Cited by 20 | Viewed by 3988

Abstract

Aging is associated with an increase in stroke risk. Melatonin, a potent free radical scavenger and broad spectrum antioxidant, has been shown to counteract inflammation and apoptosis in brain injury. However, little is known on the possible protective effects of melatonin in aged [...] Read more.

Aging is associated with an increase in stroke risk. Melatonin, a potent free radical scavenger and broad spectrum antioxidant, has been shown to counteract inflammation and apoptosis in brain injury. However, little is known on the possible protective effects of melatonin in aged individuals affected by brain ischemia. Also, using melatonin before or after an ischemic stroke may result in significantly different molecular outcomes. The objective of the present study was to compare the effects of pre-ischemia vs. post-ischemia melatonin administration in an ischemic lesion in the cortex and hippocampus of senescent Wistar rats. An obstruction of the middle cerebral artery (MCA) to 18-month-old animals was performed. In general, animals treated with melatonin from 24 h prior to surgery until 7 days after the surgical procedure (PrevT) experienced a significant decrease in the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), glial fibrillary acidic protein (GFAP), Bcl-2-associated death promoter (BAD), and Bcl-2-associated X protein (BAX) in both cortex and hippocampus, while hippocampal levels of sirtuin 1 (SIRT1) and B-cell lymphoma 2 (Bcl-2) increased. Treatment of animals with melatonin only after surgery (AT) resulted in similar effects, but to a lesser extent than in the PrevT group. In any case, melatonin acted as a valuable therapeutic agent protecting aged animals from the harmful effects of cerebral infarction. Full article

(This article belongs to the Special Issue Immunosenescence and Related Processes)

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15 pages, 1318 KiB

Open AccessArticle

Protein Carbamylation: A Marker Reflecting Increased Age-Related Cell Oxidation

by Julia Carracedo, Rafael Ramírez-Carracedo, Irene Martínez de Toda, Carmen Vida, Matilde Alique, Mónica De la Fuente and Rafael Ramírez-Chamond

Int. J. Mol. Sci. 2018, 19(5), 1495; https://doi.org/10.3390/ijms19051495 - 17 May 2018

Cited by 32 | Viewed by 5582

Abstract

Carbamylation is a post-translational modification of proteins that may partake in the oxidative stress-associated cell damage, and its increment has been recently proposed as a “hallmark of aging”. The molecular mechanisms associated with aging are related to an increased release of free radicals. [...] Read more.

Carbamylation is a post-translational modification of proteins that may partake in the oxidative stress-associated cell damage, and its increment has been recently proposed as a “hallmark of aging”. The molecular mechanisms associated with aging are related to an increased release of free radicals. We have studied whether carbamylated proteins from the peripheral blood of healthy subjects are related to oxidative damage and aging, taking into account the gender and the immune profile of the subjects. The study was performed in healthy human volunteers. The detection of protein carbamylation and malondialdehyde (MDA) levels was evaluated using commercial kits. The immune profile was calculated using parameters of immune cell function. The results show that the individuals from the elderly group (60–79 years old) have increased carbamylated protein and MDA levels. When considered by gender, only men between 60 and 79 years old showed significantly increased carbamylated proteins and MDA levels. When those subjects were classified by their immune profile, the carbamylated protein levels were higher in those with an older immune profile. In conclusion, the carbamylation of proteins in peripheral blood is related to age-associated oxidative damage and to an aging functional immunological signature. Our results suggest that carbamylated proteins may play an important role at the cellular level in the aging process. Full article

(This article belongs to the Special Issue Immunosenescence and Related Processes)

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Review

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12 pages, 661 KiB

Open AccessReview

Mitochondrial Dysfunction and Aging: Insights from the Analysis of Extracellular Vesicles

by Anna Picca, Flora Guerra, Riccardo Calvani, Cecilia Bucci, Maria Rita Lo Monaco, Anna Rita Bentivoglio, Hélio José Coelho-Júnior, Francesco Landi, Roberto Bernabei and Emanuele Marzetti

Int. J. Mol. Sci. 2019, 20(4), 805; https://doi.org/10.3390/ijms20040805 - 13 Feb 2019

Cited by 120 | Viewed by 11155

Abstract

The progressive decline of cell function and integrity, manifesting clinically as increased vulnerability to adverse outcomes and death, is core to biological aging. Mitochondrial dysfunction, oxidative stress, altered intercellular communication (including chronic low-grade inflammation), genomic instability, telomere attrition, loss of proteostasis, altered nutrient [...] Read more.

The progressive decline of cell function and integrity, manifesting clinically as increased vulnerability to adverse outcomes and death, is core to biological aging. Mitochondrial dysfunction, oxidative stress, altered intercellular communication (including chronic low-grade inflammation), genomic instability, telomere attrition, loss of proteostasis, altered nutrient sensing, epigenetic alterations, and stem cell exhaustion have been proposed as hallmarks of aging. These “aging pillars” are not mutually exclusive, making the matter intricate and leaving numerous unanswered questions. The characterization of circulating extracellular vesicles (EVs) has recently allowed specific secretory phenotypes associated with aging to be identified. As such, EVs may serve as novel biomarkers for capturing the complexity of aging. Besides the mitochondrial–lysosomal axis, EV trafficking has been proposed as an additional layer in mitochondrial quality control. Indeed, disruption of the mitochondrial–lysosomal axis coupled with abnormal EV secretion may play a role in the pathogenesis of aging and several disease conditions. Here, we discuss (1) the mechanisms of EV generation; (2) the relationship between the mitochondrial–lysosomal axis and EV trafficking in the setting of mitochondrial quality control; and (3) the prospect of using EVs as aging biomarkers and as delivery systems for therapeutics against age-related conditions. Full article

(This article belongs to the Special Issue Immunosenescence and Related Processes)

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14 pages, 897 KiB

Open AccessReview

Updates on Old and Weary Haematopoiesis

by Joanna Konieczny and Lorena Arranz

Int. J. Mol. Sci. 2018, 19(9), 2567; https://doi.org/10.3390/ijms19092567 - 29 Aug 2018

Cited by 18 | Viewed by 8774

Abstract

Blood formation, or haematopoiesis, originates from haematopoietic stem cells (HSCs), whose functions and maintenance are regulated in both cell- and cell non-autonomous ways. The surroundings of HSCs in the bone marrow create a specific niche or microenvironment where HSCs nest that allows them [...] Read more.

Blood formation, or haematopoiesis, originates from haematopoietic stem cells (HSCs), whose functions and maintenance are regulated in both cell- and cell non-autonomous ways. The surroundings of HSCs in the bone marrow create a specific niche or microenvironment where HSCs nest that allows them to retain their unique characteristics and respond rapidly to external stimuli. Ageing is accompanied by reduced regenerative capacity of the organism affecting all systems, due to the progressive decline of stem cell functions. This includes blood and HSCs, which contributes to age-related haematological disorders, anaemia, and immunosenescence, among others. Furthermore, chronological ageing is characterised by myeloid and platelet HSC skewing, inflammageing, and expanded clonal haematopoiesis, which may be the result of the accumulation of preleukaemic lesions in HSCs. Intriguingly, haematological malignancies such as acute myeloid leukaemia have a high incidence among elderly patients, yet not all individuals with clonal haematopoiesis develop leukaemias. Here, we discuss recent work on these aspects, their potential underlying molecular mechanisms, and the first cues linking age-related changes in the HSC niche to poor HSC maintenance. Future work is needed for a better understanding of haematopoiesis during ageing. This field may open new avenues for HSC rejuvenation and therapeutic strategies in the elderly. Full article

(This article belongs to the Special Issue Immunosenescence and Related Processes)

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16 pages, 1137 KiB

Open AccessReview

Unraveling the Molecular Mechanism of Immunosenescence in Drosophila

by Kyung-Jin Min and Marc Tatar

Int. J. Mol. Sci. 2018, 19(9), 2472; https://doi.org/10.3390/ijms19092472 - 21 Aug 2018

Cited by 22 | Viewed by 8070

Abstract

A common feature of the aging process is a decline in immune system performance. Extensive research has sought to elucidate how changes in adaptive immunity contribute to aging and to provide evidence showing that changes in innate immunity have an important role in [...] Read more.

A common feature of the aging process is a decline in immune system performance. Extensive research has sought to elucidate how changes in adaptive immunity contribute to aging and to provide evidence showing that changes in innate immunity have an important role in the overall decline of net immune function. Drosophila is an emerging model used to address questions related to immunosenescence via research that integrates its capacity for genetic dissection of aging with groundbreaking molecular biology related to innate immunity. Herein, we review information on the immunosenescence of Drosophila and suggest its possible mechanisms that involve changes in insulin/IGF(insulin-like growth factor)-1 signaling, hormones such as juvenile hormone and 20-hydroxyecdysone, and feedback system degeneration. Lastly, the emerging role of microbiota on the regulation of immunity and aging in Drosophila is discussed. Full article

(This article belongs to the Special Issue Immunosenescence and Related Processes)

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