Aging, imbalanced inflammation and viral infection

Goldstein, Daniel R.

doi:10.4161/viru.1.4.12009

Cited by 31 publications

(22 citation statements)

References 37 publications

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“…These data suggest that CoV adaptation to virulence is different in young and aged animals, especially when coupled with variations in virus pathogenic determinants. While immune senescence can enhance virus virulence 43 , our data support the novel hypothesis that virulent zoonotic coronaviruses may emerge more quickly after in vivo passage, especially in the aged, where multiple evolutionary pathways exist that can program virus virulence. The disproportionate identification of mutations in the accessory ORFs following passage of the CRG3 TRN virus in aged animals may reflect the roles these accessory ORFs are hypothesized to play in the modulation of host immunity 44 .…”

Section: Discussionsupporting

confidence: 74%

Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform

Graham

Deming

et al. 2018

Commun Biol

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Emerging and re-emerging zoonotic viral diseases are major threats to global health, economic stability, and national security. Vaccines are key for reducing coronaviral disease burden; however, the utility of live-attenuated vaccines is limited by risks of reversion or repair. Because of their history of emergence events due to their prevalence in zoonotic pools, designing live-attenuated coronavirus vaccines that can be rapidly and broadly implemented is essential for outbreak preparedness. Here, we show that coronaviruses with completely rewired transcription regulatory networks (TRNs) are effective vaccines against SARS-CoV. The TRN-rewired viruses are attenuated and protect against lethal SARS-CoV challenge. While a 3-nt rewired TRN reverts via second-site mutation upon serial passage, a 7-nt rewired TRN is more stable, suggesting that a more extensively rewired TRN might be essential for avoiding growth selection. In summary, rewiring the TRN is a feasible strategy for limiting reversion in an effective live-attenuated coronavirus vaccine candidate that is potentially portable across the Nidovirales order.

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Section: Discussionsupporting

confidence: 74%

Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform

Graham

Deming

et al. 2018

Commun Biol

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“…However, age and IL-6 levels were acting as confounding factors. Despite the fact that further analysis is needed to understand this result, we hypothesize whether IL-6 and neutrophilia could be indirect markers of tissue injury (Goldstein 2010;Baune et al 2011) and not the primary case leading to mortality.…”

Section: Discussionmentioning

confidence: 99%

Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans

Ferrando‐Martínez

Romero-Sánchez

Solana

et al. 2011

AGE

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Relationship between thymic function and elderly survival has been suspected, despite the fact that formal proof is elusive due to technical limitations of thymic function-related markers. The newly described sj/β-TREC ratio allows now, by overcoming these limitations, an accurate measurement of thymic output in elderly humans. Thus, the aim of this study was to determine the impact of thymic function and inflammatory markers on healthy elderly human survival. Healthy volunteers (n=151), aged over 65, were asked to participate (CARRERITAS cohort). Subjects were excluded if diagnosed of dementia or, during the last 6 months, had clinical data of infection, hospital admission, antitumor therapy, or any treatment that could influence the immune status. Thymic function (sj/β-TREC ratio), CD4:CD8 T cell ratio, C-reactive protein, interleukin-6, and neutrophilia were determined from basal samples. All basal variables and age were associated with 2-year allcause mortality. Multivariate analysis showed that only thymic function and C-reactive protein were independently associated with time to death. In conclusion, we show, for the first time, the direct role of thymic function in human survival. C-reactive protein raise is also a marker of mortality in the healthy elderly, in a thymic-independent way.

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“…In old individuals, alterations of both innate and adaptive immunity lead to increased susceptibility to infections, including periodontal inflammation [17], [18]. Age-related changes in the adaptive immune system are well-documented, such as altered cytokine patterns and a decline in Ag-presenting cell function [19].…”

Section: Introductionmentioning

confidence: 99%

Effects of Aging on Endotoxin Tolerance Induced by Lipopolysaccharides Derived from Porphyromonas gingivalis and Escherichia coli

Sun

Yang

et al. 2012

PLoS ONE

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BackgroundPeriodontitis is a bacterially induced chronic inflammatory disease. Exposure of the host to periodontal pathogens and their virulence factors induces a state of hyporesponsiveness to subsequent stimulations, termed endotoxin tolerance. Aging has a profound effect on immune response to bacteria challenge. The aim of this study was to explore the effects of aging on endotoxin tolerance induced by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) and Escherichia coli (E. coli) LPS in murine peritoneal macrophages.Methodology/Principal FindingsWe studied the cytokine production (TNF-αand IL-10) and Toll-like receptor 2, 4 (TLR2, 4) gene and protein expressions in peritoneal macrophages from young (2-month-old) and middle-aged (12-month-old) ICR mice following single or repeated P. gingivalis LPS or E. coli LPS stimulation. Pretreatment of peritoneal macrophages with P. gingivalis LPS or E. coli LPS resulted in a reduction in TNF-α production and an increase in IL-10 production upon secondary stimulation (p<0.05), and the markedly lower levels of TNF-α and higher levels of IL-10 were observed in macrophages from young mice compared with those from middle-aged mice (p<0.05). In addition, LPS restimulations also led to the significantly lower expression levels of TLR2, 4 mRNA and protein in macrophages from young mice (p<0.05).Conclusions/SignificanceRepeated LPS stimulations triggered endotoxin tolerance in peritoneal macrophages and the ability to develop tolerance in young mice was more excellent. The impaired ability to develop endotoxin tolerance resulted from aging might be related to TLR2, 4 and might lead to the incontrollable periodontal inflammation in older adults.

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Aging, imbalanced inflammation and viral infection

Cited by 31 publications

References 37 publications

Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform

Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform

Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans

Effects of Aging on Endotoxin Tolerance Induced by Lipopolysaccharides Derived from Porphyromonas gingivalis and Escherichia coli

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