The Immune System and Its Dysregulation with Aging

Müller, Ludmila; Benedetto, Svetlana Di; Pawelec, Graham

doi:10.1007/978-981-13-3681-2_2

Cited by 202 publications

(190 citation statements)

References 107 publications

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“…The thymus, as a central immune organ, is the main site for generation of naive T lymphocytes [43]. Thymus atrophy is considered to be a biomarker of immune system aging and is influenced by many factors, such as age, hormones, and gender [44]. Studies have extensively demonstrated that ovariectomy or orchiectomy can result in transient thymic regeneration.…”

Section: Discussionmentioning

confidence: 99%

Effects of Castration on miRNA, lncRNA, and mRNA Profiles in Mice Thymus

Zhang

et al. 2020

Genes

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Thymic degeneration and regeneration are regulated by estrogen and androgen. Recent studies have found that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in organ development. In this study, RNA sequencing (RNA-seq) results showed that ovariectomy significantly affected 333 lncRNAs, 51 miRNAs, and 144 mRNAs levels (p < 0.05 and |log2fold change| > 1), and orchiectomy significantly affected 165 lncRNAs, 165 miRNAs, and 208 mRNA levels in the thymus. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that differentially expressed genes (DEGs) were closely related to cell development and immunity. Next, we constructed two lncRNA–miRNA–mRNA networks using Cytoscape based on the targeting relationship between differentially expressed miRNAs (DEMs) and DEGs and differentially expressed lncRNAs (DELs) analyzed by TargetScan and miRanda. Besides, we screened DEGs that were significantly enriched in GO and in ceRNA networks to verify their expression in thymocytes and thymic epithelial cells (TECs). In addition, we analyzed the promoter sequences of DEGs, and identified 25 causal transcription factors. Finally, we constructed transcription factor-miRNA-joint target gene networks. In conclusion, this study reveals the effects of estrogen and androgen on the expression of miRNAs, lncRNAs, and mRNAs in mice thymus, providing new insights into the regulation of thymic development by gonadal hormones and non-coding RNAs.

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Section: Discussionmentioning

confidence: 99%

Effects of Castration on miRNA, lncRNA, and mRNA Profiles in Mice Thymus

Zhang

et al. 2020

Genes

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“…This chronic stimulation causes these memory cells to become exhausted and no longer able to function, contributing to an increased susceptibility of elderly to infectious pathogens [79,80]. The aging immune system is also characterized by a decline in the numbers of naive T cells, an imbalance in Th1/Th2 cell subsets, and a decrease in T cell receptor (TCR) repertoire [75,81,82].…”

Section: Immunomodulatation Of the Elderly Immune Systemmentioning

confidence: 99%

Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak

Har-Noy

2020

J Transl Med

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Background: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next 'Disease X' . Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim ® ) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim ® creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-ϒ, leading to development of an "anti-viral state", by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allospecific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-ϒ, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/ CTL in circulation capable of responding to the next viral encounter. Conclusion:Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism.

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“…However, many differences between the younger and older generation are in fact only assumed to be detrimental without unequivocal evidence. It is clear that ageing process does not always lead to predictable decline in immune functions but it does lead to their alterations [2].…”

Section: Introductionmentioning

confidence: 99%

Immunosenescence of Lymphocytes T and Implications for Age-Related Disorders

Tylutka

Morawin

Gramacki

et al. 2020

Preprint

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Background. The decrease in immunity with age is still a major health concern as elderly people are more susceptible to infections and increased incidence of autoimmunity. Consequently, there is an increasing interest in immunosenescence and changes in immunology cells like T cells. The aim of our study was to find a disproportion in subpopulation of T cells as well as CD4/CD8 ratio depending on the age, gender or comorbidities. Results. In the present study, a flow cytometry was used to indicate the differences between age, sex, disorders and fat content in the CD4+ and CD8+ T cells population divided into naïve and memory cells as well as CD4/CD8 ratio in people aged 71.9± 5.8 years (females n=83, males n=16) compared to young people aged 20.6 ± 1.1 years (females n=12, males n=19). The percentage of naïve CD4+ and CD8+ cells was found to be statistically significantly lower in the elderly compared to the young. In addition, gender was observed to play an important role in the outcomes in the analysed subpopulations and in female group, who live statistically longer than males, our older group of Polish women demonstrated a significantly higher percentage of naïve lymphocytes in both the CD4+ and CD8+ populations compared to men. The CD4/CD8 ratio increases with age, which can be considered one of the markers determining longevity. Elderly people with age-related diseases (hypertension) also show an increased level of CD4/CD8 ratio as well as CD4+. Conclusion. We demonstrated that changes in the T cells population, including naïve cell population as well as CD4/CD8 ratio, are important markers which can be predictive of healthy status. In order to accurately determine longevity, gender or age-associated diseases should be taken into account.

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The Immune System and Its Dysregulation with Aging

Cited by 202 publications

References 107 publications

Effects of Castration on miRNA, lncRNA, and mRNA Profiles in Mice Thymus

Effects of Castration on miRNA, lncRNA, and mRNA Profiles in Mice Thymus

Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak

Immunosenescence of Lymphocytes T and Implications for Age-Related Disorders

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