Restoration of the Thymus in Aging Mice by in Vivo Zinc Supplementation

Dardenne, Mireille; Boukaïba, Nadia; Gagnerault, Marie‐Claude; Homo‐Delarche, Françoise; Chappuis, P.; Lemonnier, Daniel; Savino, Wilson

doi:10.1006/clin.1993.1016

Cited by 72 publications

(31 citation statements)

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“…Recently, a physiological zinc supplementation (18 mg/ml Zn 2 + + in the drinking water for 1 month) in old mice induced thymus re-growth and its endocrine activity coupled with an improvement of peripheral NK (natural killer) cell cytotoxicity (40,46) . Zinc supplementation (300 mg/kg for 25 d) in aged mice improved thymopoiesis, as assessed by increased total thymocyte numbers (47) .…”

Section: Effect Of Zinc Supplementation On Inflammatory/ Immune Respomentioning

confidence: 99%

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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: Effect Of Zinc Supplementation On Inflammatory/ Immune Respomentioning

confidence: 99%

“…Increased number of thymic lymphocytes without significant changes in CD4/CD8 thymocyte subsets; increased thymulin levels (46) …”

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

Zinc, metallothioneins and immunosenescence

et al. 2010

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“…Moreover, the copper to zinc ratio may be more informative than zinc alone, as this ratio may tell us something about the systemic redox balance of the individual (523). This has practical implications, because even if absorption is compromised in the elderly, sufficient supplementation might still overcome the problem (524). In rats, there is also a decrease in serum zinc, and the levels found in the thymus are lower compared to young animals as well (525).…”

Section: Vitamins and Minerals; Anti-oxidantsmentioning

confidence: 99%

T cells and aging update February 1999

Pawelec¹

1999

Front Biosci

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T cell immunosenescence 218effects of dysregulated immune responses in the elderly by supplementation or other approaches may result in an enhancement of their quality of life, and significant reductions in the cost of medical care in old age. FACTORS CONTRIBUTING TO IMMUNO-SENESCENCE HematopoiesisDysregulated hematopoiesis is seen in elderly individuals, raising the possibility that this could contribute to altered immune function in the aged. Hematopoiesis in man may be compromised because of a severely reduced capacity to produce colony stimulating factors (44) and increased production of pro-inflammatory factors such as IL 6 (45), because lower numbers of progenitor cells are present in the BM (46) and because of an age-related decline in proliferative potential of putative haematopoietic stem cells (HSC) (47). In mice, the repopulating potential of murine fetal liver-derived HSC is higher than that of adult BM-derived stem cells (48), suggesting possible aging of the HSC themselves. Normal cells with shorter telomeres possess less remaining replicative capacity than those with longer telomeres (see section 5.2). Accordingly, HSC from adult BM were found to have shorter telomeres than fetal liver-derived or umbilical cord-derived stem cells, consistent with aging of HSC (49). Telomere lengths decreased on culture despite low level expression of telomerase in these cells (50,51), although the rate of basepair loss per population doubling of cells in culture was lower during the first two weeks, when telomerase was upregulated, than in the next two, when it was downregulated (52). The telomerase expressed is therefore functionally active but may not be able to completely maintain telomere length in aging HSC cells. True embryonic stem cells (ESC), on the other hand, which may really be immortal, do retain high levels of telomerase activity (53). On the other hand, ESC from telomerase-knockout mice show gradual telomere shortening over many population doublings (PD) resulting in slowing and eventual cessation of growth (54). Certain animals which do not downregulate telomerase manifest a permanent growth phase and little or no senescence (55,56).

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“…These data suggest that LPS mitogen may be also considered to test T cell-mediated immunity, even if the LPS mitogen is not the optimal for this purpose. Consequently, benefits on the T cellmediated immunity occur, via thymulin and IFN-γ release, coupled with new maturation and differentiation of naive T cells within the thymus, as shown by increased thymic output (Wong et al 2009) and by a restoration of the CD4/CD8 ratio (Dardenne et al 1993) after zinc supplementation in ageing. Moreover, the major zinc release also occurs in the presence of LPS stimulation coupled with augmented IFN-γ release after the zinc trial (Table 3).…”

Section: Discussionmentioning

confidence: 99%

Effects of zinc-fortified drinking skim milk (as functional food) on cytokine release and thymic hormone activity in very old persons: a pilot study

Costarelli

Giacconi

Malavolta

et al. 2014

AGE

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Zinc is a relevant nutritional factor for the whole life of an organism because it affects the inflammatory/immune response and antioxidant activity, leading to a healthy state. Despite its important function, the dietary intake of zinc is inadequate in elderly. Possible interventions include food fortification because it does not require changes in dietary patterns, the cost is low and it can reach a large portion of the elderly population, including very old subjects. Studies evaluating the impact of Zn-fortified foods on functional parameters in elderly, in particular, in very old individuals, are missing. The objective of this study was to evaluate the efficacy of consumption of a zinc-fortified drinking skim milk (Zn-FMilk) for a period of 2 months in comparison to standard non-fortified milk (No-FMilk) on some biochemical parameters, zinc status, inflammatory/immune response and on a key parameter of the T cell-mediated immunity (thymulin hormone) in healthy very old subjects. The treatment with zinc-fortified milk (Zn-FMilk) is a good omen to increase the cell-mediated immunity in very old age represented by thymulin activity and some cytokine (IL-12p70, IFN-γ) release. At clinical level, a good healthy state occurs in 70 % of the subjects with no hospitalization after 1 year of the follow-up in comparison to very old control subjects that did not participate to crossover design. In conclusion, the Zn-FMilk can be considered a good functional food for elderly, including older people. It might be a good replacement to the zinc tablets or lozenges taking into account the attitude of old people to uptake milk as a preferential food.

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Restoration of the Thymus in Aging Mice by in Vivo Zinc Supplementation

Cited by 72 publications

References 0 publications

Zinc, metallothioneins and immunosenescence

Zinc, metallothioneins and immunosenescence

T cells and aging update February 1999

Effects of zinc-fortified drinking skim milk (as functional food) on cytokine release and thymic hormone activity in very old persons: a pilot study

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