High dietary intake of vitamin C suppresses age-related thymic atrophy and contributes to the maintenance of immune cells in vitamin C-deficient senescence marker protein-30 knockout mice

Uchio, Ryusei; Hirose, Yasuyuki; Murosaki, Shinji; Yamamoto, Yoshihiro; Ishigami, Akihito

doi:10.1017/s0007114514003857

Cited by 33 publications

(33 citation statements)

References 42 publications

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“…In an aging mouse model with vascular endothelium damage, antioxidant therapy can alleviated the dysfunction of aging vascular endothelium cells (4). Studies have shown that long-term addition of the antioxidant vitamin C (VC), which can reduce the immune levels associated with thymic aging (5). VC may also be involved in the function of cardiovascular endothelial cells (6), which can improve endothelial dysfunction in patients with hypertension (7).…”

Section: Introductionmentioning

confidence: 99%

Piwi-interacting RNAs play a role in vitamin C-mediated effects on endothelial aging

Zheng

Huang

et al. 2020

Int. J. Med. Sci.

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The underlying mechanisms that mediate the effects of vitamin C on endothelial cell aging are widely unknown. To investigate whether Piwi-interacting RNAs (piRNAs) are involved in this process, an endothelial aging model was induced in vitro using H2O2 in human umbilical vein endothelial cells (HUVECs) and then treated with vitamin C (VC). Untreated HUVECs without H2O2 exposure were used to serve as the negative control group. Cell cycle, cell viability, and aging-associated protein expression were assessed, and RNA sequencing was performed to reveal the piRNA profile. Functional and regulatory networks of the different piRNA target genes were predicted by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) analysis. H2O2 induced G1 phase cell arrest, decreased cell viability, and upregulated the senescence marker p16 in HUVECs. We found that VC treatment inhibited G1 phase cell arrest, increased the number of cells in the S and G2/M phases, increased cell viability, and decreased p16 expression. The piRNA expression profiles revealed that a large proportion of piRNAs that were differentially expressed in H2O2-treated HUVECs were partly normalized by VC. Furthermore, a number of piRNAs associated with the response to VC in H2O2-treated HUVECs were linked with senescence and cell cycle-related pathways and networks. These results indicate that the ability of VC to attenuate H2O2-mediated endothelial cell senescence may be associated with changes in expression of piRNAs that are linked to the cell cycle.

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Section: Introductionmentioning

confidence: 99%

Piwi-interacting RNAs play a role in vitamin C-mediated effects on endothelial aging

Zheng

Huang

et al. 2020

Int. J. Med. Sci.

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“…Increased ROS observed in thymocytes often leading to apoptosis, and its inhibition has been shown to rescue thymic atrophy induced by various conditions . To study the roles of ROS during the various models of thymic atrophy, we used the ROS quencher, NAC.…”

Section: Resultsmentioning

confidence: 99%

“…One of the host‐induced factors is the generation of ROS. The involvement of ROS in thymic atrophy is well documented and the supplementation of ROS quenchers or inhibitors is successful in reducing the extent of atrophy during ageing, viral infection and tumour growth in mice. Antioxidants such as NAC and vitamin C have been successful in increasing the survival and numbers of CD4 + T cells in the periphery of HIV patients.…”

Section: Discussionmentioning

confidence: 99%

“…Increased ROS observed in thymocytes 30 often leading to apoptosis, and its inhibition has been shown to rescue thymic atrophy induced by various conditions. [30][31][32][33] To study the roles of ROS during the various models of thymic atrophy, we used the ROS quencher, NAC. The thymocytes from control, infected and treated mice were stained with DCFDA to detect intracellular ROS.…”

Section: Ros Mediate Thymocyte Loss During S Typhimuriumand Lps-indumentioning

confidence: 99%

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Comparative analysis of thymic subpopulations during different modes of atrophy identifies the reactive oxygen species scavenger, N‐acetyl cysteine, to increase the survival of thymocytes during infection‐induced and lipopolysaccharide‐induced thymic atrophy

et al. 2019

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Summary The development of immunocompetent T cells entails a complex pathway of differentiation in the thymus. Thymic atrophy occurs with ageing and during conditions such as malnutrition, infections and cancer chemotherapy. The comparative changes in thymic subsets under different modes of thymic atrophy and the mechanisms involved are not well characterized. These aspects were investigated, using mice infected with Salmonella Typhimurium, injection with lipopolysaccharide (LPS), an inflammatory but non‐infectious stimulus, etoposide (Eto), a drug used to treat some cancers, and dexamethasone (Dex), a steroid used in some inflammatory diseases. The effects on the major subpopulations of thymocytes based on multicolour flow cytometry studies were, first, the CD4− CD8− double‐negative (DN) cells, mainly DN2–4, were reduced with infection, LPS and Eto treatment, but not with Dex. Second, the CD8+ CD3lo immature single‐positive cells (ISPs) were highly sensitive to infection, LPS and Eto, but not Dex. Third, treatment with LPS, Eto and Dex reduced all three subpopulations of CD4+ CD8+ double‐positive (DP) thymocytes, i.e. DP1, DP2 and DP3, but the DP3 subset was relatively more resistant during infection. Fourth, both CD4+ and CD8+ single‐positive (SP) thymocytes were lowered by Eto and Dex, but not during infection. Notably, LPS lowered CD4+ SP subsets, whereas the CD8+ SP subsets were relatively more resistant. Interestingly, the reactive oxygen species quencher, N‐acetyl cysteine, greatly improved the survival of thymocytes, especially DNs, ISPs and DPs, during infection and LPS treatment. The implications of these observations for the development of potential thymopoietic drugs are discussed.

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“…Another study showed that oral supplementation of vitamin C in mice exposed to a chemotherapeutic agent was not able to prevent a decrease in total leukocytes, lymphocytes and neutrophils counts 32 . However, long-term high-dose intake of vitamin C is effective in the maintenance of immune cells 33 .…”

Section: Discussionmentioning

confidence: 99%

The effect of vitamin C supplementation on neutropenia induced by cyclophosphamide in mice

et al. 2019

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Neutropenia is one of the adverse effects caused by the administration of chemotherapy drugs. The present study aimed at investigating the effect of vitamin C supplementation in a model of immunosuppression induced by cyclophosphamide in mice. Vitamin C supplementation (50 mg/kg/day) administered intraperitoneally (i.p.) for 7 consecutive days in adult Swiss albino female. Mice were divided into four groups (n= 8/group): 1. Control (only distilled water i.p.), 2. Cyclophosphamide group (cyclophosphamide i.p. 150 and 100 mg/kg on days 1 and 4, respectively and distilled water daily), 3. Vitamin C group (Vitamin C 50 mg/kg i.p. and distilled water daily), and 4. Cyclophosphamide and Vitamin C group (cyclophosphamide i.p. 150 and 100 mg/kg on days 1 and 4, respectively and vitamin C 50 mg/kg i.p. daily). Vitamin C did not interfere in leukocytes count, but when co-administered with cyclophosphamide, significant interaction was observed, intensifying the neutropenia caused by cyclophosphamide. Vitamin C did not influence body weight during treatment, but groups receiving cyclophosphamide had a significant weight loss from the third day of treatment until the end of experiment compared to the control group. Vitamin C supplementation intensified neutropenia induced by cyclophosphamide and did not prevent weight loss induced by cyclophosphamide in mice.

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High dietary intake of vitamin C suppresses age-related thymic atrophy and contributes to the maintenance of immune cells in vitamin C-deficient senescence marker protein-30 knockout mice

Cited by 33 publications

References 42 publications

Piwi-interacting RNAs play a role in vitamin C-mediated effects on endothelial aging

Piwi-interacting RNAs play a role in vitamin C-mediated effects on endothelial aging

Comparative analysis of thymic subpopulations during different modes of atrophy identifies the reactive oxygen species scavenger, N‐acetyl cysteine, to increase the survival of thymocytes during infection‐induced and lipopolysaccharide‐induced thymic atrophy

The effect of vitamin C supplementation on neutropenia induced by cyclophosphamide in mice

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