Rebalancing the unbalanced aged immune system – A special focus on zinc

Baarz, Bastian Robinson; Rink, Lothar

doi:10.1016/j.arr.2021.101541

Cited by 17 publications

(12 citation statements)

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“…Means not sharing any letter ( a or b ) indicate statistical significance (p < 0.05) 3 One-way ANOVA and Tukey´s post-test. Means not sharing any letter ( a or b ) indicate statistical significance (p < 0.05) 4 under categories; while a hospitalization can, of course, have several reasons, for the sake of clarity we decided to indicate the most predominant one in each case 5 On the other hand, the initial determination of the zinc status of each subject allowed us to interpret the data obtained by CREM α and IL-2 measurements and to test them for possible mutual correlations.…”

Section: Table 1 Characteristics Of the Study Participantsmentioning

confidence: 99%

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Short-term zinc supplementation of zinc-deficient seniors counteracts CREMα - mediated IL-2 suppression

et al. 2022

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Background Aging is accompanied by a dramatic decline in the interleukin (IL)-2 production capacity of human immune cells, thus making seniors more susceptible to a variety of age-related diseases. A common cause of impaired cytokine production in advanced age is a deficiency of the essential micronutrient zinc. Nevertheless, the molecular mechanisms underlying a zinc deficiency-induced decrease in IL-2 production have not yet been satisfactorily elucidated. Recent animal and in vitro data suggested that the transcription factor cAMP-responsive element modulator (CREM) $$\alpha$$ α plays a critical role in T cells´ disturbed IL-2 production in suboptimal zinc conditions. However, its role in the human aging process and the possibility of influencing this detrimental process by short-term zinc supplementation have not yet been evaluated. Results Comparing peripheral lymphocytes of 23 young and 31 elderly subjects with either high, intermediate, or deficient zinc status, we observed zinc-dependent regulation of the IL-2 production mediated by the transcription factor CREM $$\alpha$$ α . For the first time in humans, we report a mutual relationship between low zinc levels, high CREM $$\alpha$$ α expression, subsequent impaired IL-2 production, and vice versa. Remarkably, an average of only 6 days of in vivo zinc supplementation to zinc-deficient seniors was sufficient to rapidly improve zinc status, reverse CREM $$\alpha$$ α overexpression, and counteract subsequent low IL-2 production rates. Conclusions Our ex vivo and in vivo data identify zinc deficiency-mediated CREM $$\alpha$$ α overexpression as a key cellular mechanism underlying impaired IL-2 production in the elderly and point toward the use of zinc as a rapidly immune-enhancing add-on nutraceutical in geriatric therapy. Graphical abstract During the aging process, there is a progressive decrease in zinc status, which in turn leads to overexpression of the transcription factor CREM$$\mathrm{\alpha }$$ α in peripheral lymphocytes. CREMα is a negative regulator of the IL-2 gene, the overexpression of which dramatically limits adequate IL-2 production. This deleterious mechanism can be counteracted by short-term oral zinc administration, which can adjust IL-2 production in old, zinc-deficient individuals to a level similar to that of young adults.

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Section: Table 1 Characteristics Of the Study Participantsmentioning

confidence: 99%

“…The human aging process is well described to not spare the immune system [ 1 , 2 ]. As part of the search for potentially mitigable or even reversible age-related immune impairments, the suboptimal zinc status of old persons came into focus early on [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Short-term zinc supplementation of zinc-deficient seniors counteracts CREMα - mediated IL-2 suppression

et al. 2022

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“…Zinc is an abundant trace mineral in the body, and is a part of over 600 enzymes, numerous proteins, and over 2500 transcription factors ( King et al, 2015 ; Kambe et al, 2015 ). Zinc is essential for numerous biological processes, including cellular apoptosis, immune function, brain maturation and development, taste and smell regulation, skin and mucosal integrity, and metabolic function ( Kodama et al, 2020 ; Baarz and Rink, 2022 ; Brion et al, 2021 ; Beigi Harchegani et al, 2020 ). It is used as a signaling ion to regulate gene expression, protein synthesis, DNA synthesis, and cell division.…”

Section: Introductionmentioning

confidence: 99%

Zinc and its role in vitamin D function

Amos

2022

Current Research in Physiology

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“…Among minerals, the role of zinc is recognized as of particular significance in countering immunological aging (Baarz and Rink 2022 ). That elderly are often deficient in zinc suggesting a direct correlation between chronic inflammation, immunosenescence, and increased susceptibility to infections (Cabrera 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Emerging cellular senescence-centric understanding of immunological aging and its potential modulation through dietary bioactive components

et al. 2022

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Immunological aging is strongly associated with the observable deleterious effects of human aging. Our understanding of the causes, effects, and therapeutics of aging immune cells has long been considered within the sole purview of immunosenescence. However, it is being progressively realized that immunosenescence may not be the only determinant of immunological aging. The cellular senescence-centric theory of aging proposes a more fundamental and specific role of immune cells in regulating senescent cell (SC) burden in aging tissues that has augmented the notion of senescence immunotherapy. Now, in addition, several emerging studies are suggesting that cellular senescence itself may be prevalent in aging immune cells, and that senescent immune cells exhibiting characteristic markers of cellular senescence, similar to non-leucocyte cells, could be among the key drivers of various facets of physiological aging. The present review integrates the current knowledge related to immunosenescence and cellular senescence in immune cells per se, and aims at providing a cohesive overview of these two phenomena and their significance in immunity and aging. We present evidence and rationalize that understanding the extent and impact of cellular senescence in immune cells vis-à-vis immunosenescence is necessary for truly comprehending the notion of an ‘aged immune cell’. In addition, we also discuss the emerging significance of dietary factors such as phytochemicals, probiotic bacteria, fatty acids, and micronutrients as possible modulators of immunosenescence and cellular senescence. Evidence and opportunities related to nutritional bioactive components and immunological aging have been deliberated to augment potential nutrition-oriented immunotherapy during aging.

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Rebalancing the unbalanced aged immune system – A special focus on zinc

Cited by 17 publications

References 369 publications

Short-term zinc supplementation of zinc-deficient seniors counteracts CREMα - mediated IL-2 suppression

Short-term zinc supplementation of zinc-deficient seniors counteracts CREMα - mediated IL-2 suppression

Zinc and its role in vitamin D function

Emerging cellular senescence-centric understanding of immunological aging and its potential modulation through dietary bioactive components

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