Aging-associated immunosenescence via alterations in splenic immune cell populations in rat

El-naseery, Nesma I.; Mousa, Hanaa S.E.; Noreldin, Ahmed E.; El‐Far, Ali H.; Elewa, Yaser Hosny Ali

doi:10.1016/j.lfs.2019.117168

Cited by 27 publications

(19 citation statements)

References 68 publications

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“…Infected myeloid cells had almost no SOD. These data correlate with studies that showed that lower levels of SOD in rats resulted in significantly reduced spleen sizes, reduced number of T-cells and macrophages (among others), increases in oxidative stress in splenic tissues, and shorter lifespans [152]. Additionally, the importance of peroxisome-related enzymes to cell survival was validated by the addition of exogenous CAT/SOD, showing that CAT rescues viability in myeloid cells only, SOD rescues viability in both myeloid and T-cells ( Figure 1C).…”

Section: Discussionsupporting

confidence: 88%

Low-Level Ionizing Radiation Induces Selective Killing of HIV-1-Infected Cells with Reversal of Cytokine Induction Using mTOR Inhibitors

Pinto

DeMarino

et al. 2020

Viruses

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HIV-1 infects 39.5 million people worldwide, and cART is effective in preventing viral spread by reducing HIV-1 plasma viral loads to undetectable levels. However, viral reservoirs persist by mechanisms, including the inhibition of autophagy by HIV-1 proteins (i.e., Nef and Tat). HIV-1 reservoirs can be targeted by the “shock and kill” strategy, which utilizes latency-reversing agents (LRAs) to activate latent proviruses and immunotarget the virus-producing cells. Yet, limitations include reduced LRA permeability across anatomical barriers and immune hyper-activation. Ionizing radiation (IR) induces effective viral activation across anatomical barriers. Like other LRAs, IR may cause inflammation and modulate the secretion of extracellular vesicles (EVs). We and others have shown that cells may secrete cytokines and viral proteins in EVs and, therefore, LRAs may contribute to inflammatory EVs. In the present study, we mitigated the effects of IR-induced inflammatory EVs (i.e., TNF-α), through the use of mTOR inhibitors (mTORi; Rapamycin and INK128). Further, mTORi were found to enhance the selective killing of HIV-1-infected myeloid and T-cell reservoirs at the exclusion of uninfected cells, potentially via inhibition of viral transcription/translation and induction of autophagy. Collectively, the proposed regimen using cART, IR, and mTORi presents a novel approach allowing for the targeting of viral reservoirs, prevention of immune hyper-activation, and selectively killing latently infected HIV-1 cells.

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Section: Discussionsupporting

confidence: 88%

Low-Level Ionizing Radiation Induces Selective Killing of HIV-1-Infected Cells with Reversal of Cytokine Induction Using mTOR Inhibitors

Pinto

DeMarino

et al. 2020

Viruses

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“…Toll-like receptor 4 (TLR4) is the main receptor for lipopolysaccharides (LPS) present in gram-negative bacteria (9). The TLR4 protein functions as a key regulator of periodontitis by modulating cell signal transduction, apoptosis, and the quality and magnitude of immune responses (10,11). Polymorphisms in the TLR4 gene are associated with increased risk of periodontitis (12).…”

Section: Introductionmentioning

confidence: 99%

Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression

Qin

Chen

et al. 2020

Int J Mol Med

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Overproduction of pro-inflammatory cytokines in the aged, which is called inflammaging, leads to the deterioration of periodontitis. Toll-like receptor 4 (TLR4) plays a role in the regulation of cellular senescence, and its expression increases with age. However, there has been limited research into the molecular mechanisms underlying the onset of periodontal inflammaging, and the interplay between TLR4 and inflammaging. In the present study, wild-type and TLR4 gene knockout mice were used to investigate the activation of the TLR4 pathway in mouse periodontitis and the expression of the nucleotide-binding and oligomerization domain-like receptor 3 (NLRP3) inflammasome, an upstream immune checkpoint during the development of inflammaging. Activation of TLR4 in a mouse model of periodontitis enhanced the expression of a senescence-associated secretory phenotype (SASP), which boosted the inflammaging process. Conversely, TLR4 activation downregulated the expression of B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and promoted the priming of NLRP3 inflammasome, both of which are regulators of SASP. Treating gingival fibroblasts with Bmi-1 inhibitor PTC209, it was demonstrated that TLR4 activated the NLRP3 pathway and the inflammaging process by suppressing Bmi-1. In addition, there was a significant reduction in the expression of Bmi-1 expression in the gingiva of patients with periodontitis compared with healthy controls. In conclusion, the present study demonstrated that TLR4 acted by inhibiting Bmi-1 to enhance the NLRP3 pathway and SASP factors. This cascade of reactions may contribute to the senescence of the periodontium.

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“…The spleen is the most important secondary lymphoid organ in the body. It contains nearly one-fourth of all lymphocytes necessary for innate and adaptive immune responses, and it is the center of cellular and humoral immunity (El-naseery et al, 2020). The spleen structure of the oxidatively damaged mice disappeared, the shape was irregular, the red pulp myelinous sinus expanded and was filled with a large number of red blood cells, the white pulp lymphocytes were reduced, the red pulp myelin was narrowed, and the cells were sparsely arranged.…”

Section: Discussionmentioning

confidence: 99%

Determination of Polyphenols in Ilex kudingcha and Insect Tea (Leaves Altered by Animals) by Ultra-high-performance Liquid Chromatography-Triple Quadrupole Mass Spectrometry (UHPLC-QqQ-MS) and Comparison of Their Anti-Aging Effects

Yang

Tan

et al. 2021

Front. Pharmacol.

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Ilex kudingcha C.J. Tseng tea and insect tea, as traditional Chinese teas, are favored for their original craftsmanship, unique flavor, and biological functionality. In this study, ultra high-performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ-MS) was used to analyze the bioactive components of the extracts of Ilex kudingcha and insect tea, and D-galactose-induced aging mice were used to compare the in vivo anti-aging effects of Ilex kudingcha and insect tea extracts. The results were remarkable, UHPLC-QqQ-MS analysis showed that ITP contains 29 ingredients, while IKDCP contains 26 ingredients. However, due to the large differences in the content of the main chemical components in IKDCP and ITP, the effects are equally different. At the same time, the in vivo research results suggesting that the anti-aging effects of IKDCP and ITP (500 mg/kg) include the regulation of viscera indices of major organs; improvement in liver, skin, and spleen tissue morphology; decreased production of inflammatory cytokines; up regulation of SOD, CAT, GSH, GSH-PX, and T-AOC and down regulation of NO and MDA levels in serum and liver tissue; reductions in the concentration of pro-inflammatory factors, and increases in the concentration of anti-inflammatory factor. RT-qPCR and western blot assay also showed that IKDCP and ITP affect anti-aging by regulating the gene and protein expression of GSH-PX, GSH1, SOD1, SOD2, and CAT. The overall results indicate that ITP is more effective in treating oxidative damage in aging mice induced by D-galactose. Thus, ITP appears to be an effective functional drink owing to its rich nutritional components and anti-aging activities.

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Aging-associated immunosenescence via alterations in splenic immune cell populations in rat

Cited by 27 publications

References 68 publications

Low-Level Ionizing Radiation Induces Selective Killing of HIV-1-Infected Cells with Reversal of Cytokine Induction Using mTOR Inhibitors

Low-Level Ionizing Radiation Induces Selective Killing of HIV-1-Infected Cells with Reversal of Cytokine Induction Using mTOR Inhibitors

Toll‑like receptor 4 activates the NLRP3 inflammasome pathway and periodontal inflammaging by inhibiting Bmi‑1 expression

Determination of Polyphenols in Ilex kudingcha and Insect Tea (Leaves Altered by Animals) by Ultra-high-performance Liquid Chromatography-Triple Quadrupole Mass Spectrometry (UHPLC-QqQ-MS) and Comparison of Their Anti-Aging Effects

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