Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians

Miyaji, Chikako; Watanabe, Hirotaka; Toma, Hiromu; Akisaka, Masafumi; Tomiyama, Katsuhiro; Sato, Yoshiya; Abo, Toru

doi:10.1016/s0198-8859(00)00153-1

Cited by 99 publications

(63 citation statements)

References 46 publications

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“…Such a mechanism might be important for restoring ZnT8 gene expression in pancreatic vesicles being involved in the aetiology of type-2 diabetes (65) . Since zinc also affects the cytotoxicity of liver NKT cells bearing T-cell receptor gd (extrathymic T-cell pathway) with higher production of IFN-g in old mice (66) , the presence of satisfactory zinc ion bioavailability coupled with increased NKT cell cytotoxicity and enhanced IFN-g production in centenarians with respect to the elderly (67) strengthens the pivotal role of zinc supplementation in maintaining or improving the global immune response (thymic and extrathymic T-cell pathways) and in fighting oxidative stress and inflammation. However, since zinc also affects MT gene expression (13) , the question arises whether zinc supplementation in old age may further increase MT, causing possible major harmful effects (i.e.…”

Section: (Z)mentioning

confidence: 99%

Zinc, metallothioneins and immunosenescence

et al. 2010

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Ageing is an inevitable biological process with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. The nutritional factor, zinc, may remodel these changes with subsequent healthy ageing, because zinc improves the inflammatory/immune response as shown by in vitro and in vivo studies. The intracellular zinc homeostasis is regulated by buffering metallothioneins (MT) and zinc transporters (ZnT and ZIP families) that mediate the intracellular zinc signalling assigning to zinc a role of 'second messenger'. In ageing, the intracellular zinc homeostasis is altered, because high MT are unable to release zinc and some zinc transporters deputed to zinc influx (ZIP family) are defective leading to low intracellular zinc content for the immune efficiency. Physiological zinc supplementation in the elderly improves these functions. However, the choice of old subjects for zinc supplementation has to be performed in relation to the specific genetic background of MT and IL-6, because the latter is involved both in MTmRNA and in intracellular zinc homeostasis. Old subjects carrying GG genotypes (C-carriers) in the IL-6 -174G/C locus display high IL-6, low intracellular zinc content, impaired innate immunity and enhanced MT. Old subjects carrying GC and CC genotypes (C + carriers) display satisfactory intracellular zinc content, adequate innate immunity and are more prone to reach longevity. Zinc supplementation in old C-carriers restores natural killer cell cytotoxicity and zinc status. The genetic variations of the IL-6 -174G/C locus when associated with those of the MT1A + 647A/C locus are useful tools for the choice of old people for zinc supplementation.

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Section: (Z)mentioning

confidence: 99%

Zinc, metallothioneins and immunosenescence

et al. 2010

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“…The level of lymphocyte subsets, including T cells, B cells, NK cells and NKT cells, was examined by two-color immunofluorescence tests (11). Since thermal exposure was found to induce HLA-DR (MHC class II antigens) on lymphocyte subsets, three-color staining was also conducted to detect the expression of this antigen on cell surface.…”

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confidence: 99%

“…Since thermal exposure was found to induce HLA-DR (MHC class II antigens) on lymphocyte subsets, three-color staining was also conducted to detect the expression of this antigen on cell surface. This flow cytometric analysis was performed as previously described (11). The mAbs used here included FITC, PE, or PerCP-conjugated anti-CD3 (UCHT1), anti-CD56 (N901), anti-CD4 (RPA-T4), anti-CD8 (RPA-T8) (Beckman Coulter Inc., Fullerton, CA), anti-CD57 (HNK-1), anti-CD20 (L27), and anti-HLA-DR (L243) (Beckton-Dickinson Co., Franklin Lakes, NJ).…”

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confidence: 99%

Modulation of the endocrine and immune systems by well-controlled hyperthermia equipment

Tomiyama-Miyaji

Watanabe

Ohishi³

et al. 2007

Biomed. Res.

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Since high levels of hyperthermia induce immunosuppression to a certain extent (i.e., granulocytosis and lymphocytopenia) in patients, we applied mild hyperthermia in volunteers using equipment enabling well-controlled hyperthermia. Restricted control of rectal temperature at 39.4 (± 0.2)°C for 30 min was conducted and various parameters of the body were examined. The most prominent change observed during exposure to hyperthermia was elevated levels of pH and PO 2 in the blood, even in the venous blood. A transient elevation of ACTH, cortisol and growth hormone in the blood was also seen during this time. In parallel with this phenomenon, the number of total lymphocytes and those of its subsets (especially CD57 + or CD56 + NK cells and NKT cells) increased. More interestingly, the proportion of HLA-DR (MHC class II antigens) increased in NK and NKT cells, and their intensity on the surface of CD20 + B cells increased. These results suggest that mild hyperthermia is important for modulation of the functions of the circulatory, endocrine and immune systems.It is widely known that hyperthermia induces the production of heat shock proteins (HSPs) and that such HSPs are able to induce immunopotentiation via the augmented expression of MHC class I or II antigens on lymphocytes and tissue cells (2, 3, 10, 15). Hyperthermia is therefore expected to have potential as cancer immunotherapy. Another strategy for use of hyperthermia in cancer therapy is based on the notion that cancer cells are sensitive to thermal stress, which results in apoptotic death (5,20,23). However, we have encountered severe granulocytosis and lymphocytopenia in patients or animals during the exposure to various types of stress, including hyperthermia (4,12,16,17). This experience is contrary to our expectation for immunopotentiation by hyperthermic therapy.In light of these findings, we conducted mild hyperthermia in volunteers using the "Thercura System," a well-controlled hyperthermia device. We found that restricted control of rectum temperature to 39.4 (± 0.2)°C for 30 min was able to induce a prominent potentiation of many parameters in the circulation, endocrine system and immune system. Especially, the immunopotentiation induced by the present protocol of mild hyperthermia seems to be of great value for cancer patients and other diseased persons for treatment of their decreased levels of the immune functions.

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“…Since zinc affects also the cytotoxicity of liver NKT cells bearing TCRγδ (extrathymic T cell pathway) with higher production of IFN-γ in old mice , the presence of satisfactory zinc ion bioavailability, coupled with increased NKT cell cytotoxicity and enhanced IFN-γ production in centenarians with respect to elderly (Mocchegiani et al 2003;Miyaji et al 2000), strengthens the pivotal role of zinc supplementation in maintaining or improving the global immune response (thymic and extrathymic T cell pathways) and in fighting oxidative stress and inflammation. Some authors have also shown that zinc supplementation in combination with other micronutrients may enhance immunity without interfering on vitamin metabolism.…”

Section: Potential Usefulness Of Zn Supplementation In Elderly Subjectsmentioning

confidence: 97%

“…Findings in centenarians and in very old mice confirm the relevance of zinc in restoring NK cell function in elderly. Indeed, they have a well preserved NK cell cytotoxicity, a good zinc ion bioavailability and satisfactory IFN-γ production (Mocchegiani et al 2003;Miyaji et al 2000). A very intriguing aspect is the NKT cells bearing TCRαβ or TCRγδ that are the first defence of the organisms against virus and bacteria from early in life.…”

Section: Innate Immunitymentioning

confidence: 99%

Zinc: dietary intake and impact of supplementation on immune function in elderly

Mocchegiani

Romeo

Malavolta

et al. 2012

AGE

142

104

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The diet in the elderly does not provide a sufficient level of nutrients needed to maintain an adequate healthy status leading to micronutrient deficiencies and impaired immune response with subsequent development of degenerative diseases. Nutrient "zinc" is a relevant micronutrient involved in maintaining a good integrity of many body homeostatic mechanisms, including immune efficiency, owing to its requirement for the biological activity of many enzymes, proteins and for cellular proliferation and genomic stability. Old people aged 60-65 years and older have zinc intakes below 50% of the recommended daily allowance on a given day. Many causes can be involved: among them, altered intestinal absorption, inadequate mastication, psychosocial factors, drugs interactions, altered subcellular processes (zinc transporters (Zip and ZnT family), metallothioneins, divalent metal transporter-1). Zinc supplementation may remodel the immune alterations in elderly leading to healthy ageing. Several zinc trials have been carried out with contradictory data, perhaps due to incorrect choice of an effective zinc supplementation in old subjects showing subsequent zinc toxic effects on immunity. Old subjects with specific IL-6 polymorphism (GG allele carriers; named C−) are more prone for zinc supplementation than the entire old population, in whom correct dietary habits with foods containing zinc (Mediterranean diet) may be sufficient in restoring zinc deficiency and impaired immune response. We summarise the main causes of low zinc dietary intake in elderly reporting an update on the impact of zinc supplementation upon the immune response also on the basis of individual IL-6 polymorphism.

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Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians

Cited by 99 publications

References 46 publications

Zinc, metallothioneins and immunosenescence

Zinc, metallothioneins and immunosenescence

Modulation of the endocrine and immune systems by well-controlled hyperthermia equipment

Zinc: dietary intake and impact of supplementation on immune function in elderly

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