Life Extension - Treatment using Supplements

Zinc - updated: 16 December 2008

Zinc, metallothioneins, longevity: effect of zinc supplementation on antioxidant response: a Zincage study

Rejuvenation Res. 2008 Apr;11(2):419-23

Mocchegiani E; Zincage Consortium.

Aging is characterized by spontaneous biochemical changes that may predispose to increased susceptibility to diseases. Zinc may remodel these changes leading to healthy aging because zinc improves antioxidant defense via CLU protein and genomic stability via PARP-1 nuclear enzyme and repairs oxidized proteins via Msr A protein. The intracellular zinc homeostasis is regulated by metallothioneins (MT), which are unable in zinc release in aging, causing impaired antioxidant response restored by zinc supplementation. Here, the choice of old subjects for zinc supplementation is discussed in relation to their genetic background of MT and IL-6, because both affect intracellular zinc homeostasis.

Publication Types:

• Review

Zinc, metallothioneins, and longevity--effect of zinc supplementation: zincage study

Ann N Y Acad Sci. 2007 Nov;1119:129-46

Mocchegiani E, Giacconi R, Cipriano C, Costarelli L, Muti E, Tesei S, Giuli C, Papa R, Marcellini F, Mariani E, Rink L, Herbein G, Varin A, Fulop T, Monti D, Jajte J, Dedoussis G, Gonos ES, Trougakos IP, Malavolta M.

Aging is an inevitable biological process that is associated with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. Because nutritional factors are involved in improving immune functions, metabolic harmony, and antioxidant defense, some nutritional factors, such as zinc, may modify susceptibility to disease and promote healthy aging. In vitro (human lymphocytes exposed to endotoxins) and in vivo (old or young mice fed with low zinc dietary intake) studies revealed that zinc is important for immune efficiency (innate and adaptive), antioxidant activity (supeoxide dismutase), and cell differentiation via clusterin/apolipoprotein J. Intracellular zinc homeostasis is regulated by metallothioneins (MT) via ion release through the reduction of thiol groups in the MT molecule. This process is crucial in aging because high MT levels are not able to release zinc, resulting in low intracellular free ion availability for biological functions. Improvement in these functions occurs in the elderly after physiological zinc supplementation. In this study, the selection of elderly subjects for zinc supplementation is discussed in relation to the genetic background of MT and pro-inflammatory cytokines, such as interleukin-6, because the latter is involved both in MT-gene expression and in intracellular zinc homeostasis.

Publication Types:

• Review

Zinc and inflammatory/immune response in aging

Ann N Y Acad Sci. 2007 Apr;1100:111-22.

Vasto S, Mocchegiani E, Malavolta M, Cuppari I, Listì F, Nuzzo D, Ditta V, Candore G, Caruso C.

Life-long antigenic burden determines a condition of chronic inflammation, with increased lymphocyte activation and proinflammatory cytokine production. A large number of studies have documented changes in zinc metabolism in experimental animal models of acute and chronic inflammation and in human chronic inflammatory conditions. In particular, modification of zinc plasma concentration, as well as intracellular disturbance of antioxidant intracellular pathways, has been found in aging and in some age-related diseases. Zinc deficiency is diffused in aged individuals in order to avoid meat and other high zinc content foods due to fear of cholesterol. Rather, they increase the consumption of refined wheat products that lack zinc and other critical nutrients as a consequence of the refining process. On the other hand, plasma zinc concentration is influenced by proinflammatory cytokines (IL-6 and TNF-alpha) and by metallothioneins (MT) homeostasis, which is in turn affected by proinflammatory cytokines. MT increase in aging and chronic inflammation allowing a continuous sequestration of intracellular zinc with subsequent low zinc ion availability against stressor agents and inflammation. This phenomenon leads to an impaired inflammatory/immune response in the elderly. A major target of zinc is NF-kappaB, a transcription factor critical for the expression of proinflammatory cytokines whose production is regulated by extra- and intracellular activating and inhibiting factors interacting with the regulatory elements on cytokine genes. Effects of zinc on translocation of NF-kappaB have been attributed to the suppression of phosphorylation and degradation of the inhibitory proteins (A20) that normally sequester it in the cytoplasm. Moreover, this factor and A20 are regulated by specific genes involved in inflammation and by intracellular zinc ion availability. So, it is not so surprising that zinc deficiency is constantly observed in chronic inflammation, such as in old individuals. On the other hand, cytokine genes are highly polymorphic and some of these polymorphisms are associated with atherosclerosis and diabetes type 2. Therefore, zinc turnover, via MT homeostasis, in individuals genetically predisposed to a dysregulation of the inflammatory/immune response may play a crucial role in causing possible adverse events with the appearance of age-related diseases.

Publication Types:

• Review

Inflammation, genes and zinc in ageing and age-related diseases

Biogerontology. 2006 Oct-Dec;7(5-6):315-27

Vasto S, Mocchegiani E, Candore G, Listì F, Colonna-Romano G, Lio D, Malavolta M, Giacconi R, Cipriano C, Caruso C.

Lifelong antigenic burden determines a condition of chronic inflammation, with increased lymphocyte activation and pro-inflammatory cytokine production. A large number of studies have documented changes in Zn metabolism in experimental animal models of acute and chronic inflammation and in human chronic inflammatory diseases. In particular, modification of zinc plasma concentration as well as intracellular disturbance of antioxidant intracellular pathways have been found associated to age-related inflammatory diseases, like atherosclerosis. Zinc deficiency is extremely diffused in aged people that are educated to avoid meat and other high Zn-content foods due to fear of cholesterol. Rather, they increase consumption of refined wheat products that lack of Zn, magnesium and other critical nutrients in consequence of refining process. On the other hand, plasma concentration of metallic ions like Zn is influenced by pro-inflammatory cytokines production. A major target of Zn may be NF-kB, a transcription factor critical for the expression of many pro-inflammatory cytokines whose production is finely regulated by extra- and intracellular activating and inhibiting factors interacting with regulatory elements on cytokine genes. Moreover, this factor is regulated by the expression of specific cellular genes involved in inflammation. So it is not surprising that Zn deficiency is constantly observed in aged patients affected by infectious diseases. On the other hand, cytokine genes are highly polymorphic and some of these polymorphisms have been found associated to age-related diseases as atherosclerosis. Therefore, Zn deficiency in individuals genetically predisposed to a dis-regulation of inflammation response, may play a crucial role, in causing adverse events and in reducing the probability of a successful aging.

Publication Types:

• Review

Zinc, immune plasticity, aging, and successful aging: role of metallothionein

Ann N Y Acad Sci. 2004 Jun;1019:127-34

Mocchegiani E, Giacconi R, Muti E, Rogo C, Bracci M, Muzzioli M, Cipriano C, Malavolta M.

The capacity of the remodeling immune responses during stress (immune plasticity) is fundamental to reach successful aging. We herein report two pivotal models to demonstrate the relevance of the immune plasticity in aging and successful aging. One model is represented by the circadian rhythms of immune responses; the other one is the immune responses during partial hepatectomy/liver regeneration (pHx). The latter is suggestive because it mimics the immunosenescence and chronic inflammation 48 hours after partial hepatectomy in the young through the continuous production of IL-6, which is the main cause of immune plasticity lack in aging. The constant production of IL-6 leads to abnormal increments of zinc-bound metallothionein (MT), which is, in turn, unable in zinc release in aging. As a consequence, low zinc ion bioavailability appears for thymic and extrathymic immune efficiency, in particular, of liver NKT cells bearing TCR gd. The remodeling during the circadian cycle and during pHx of zinc-bound MT confers the immune plasticity of liver NKT gamma delta cells and NK cells in young and very old age, not in old age. Therefore, zinc-bound MT homeostasis is crucial in conferring liver immune plasticity with subsequent successful aging.

Publication Types:

• Review

Zinc nutriture in the elderly in relation to taste acuity, immune response, and wound healing

Am J Clin Nutr. 1982 Nov;36(5 Suppl):1046-59

Sandstead HH, Henriksen LK, Greger JL, Prasad AS, Good RA.

No Abstract available

Publication Types:

• Review

Publication Types:

• Review