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

Abstract

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.

Associations of Biomarkers of Atherosclerotic Plaques Instability (MMP-9, TIMP-1) and Zinc Levels in Carotid Atherosclerosis

“…В предшествующих публикациях указано на положительные и отрицательные данные по защитному эффекту цинка против атеросклероза [6,12,20].…”

Evaluation of Il-6 Production by Human Blood Cells Incubated With Metal Complexes of Γ-Globulin

“…Известно, что IL-6 усиливает экспрессию гепато-цитами специфического транспортера Zip14 [11] и, наряду с IL-1, индуцирует синтез клетками пе-чени металлотионеинов [13,18], предпочтитель-нее связывающих во внутриклеточных компар-тментах катионы цинка, нежели меди [18].…”

“…В результате, как следствие форсированной индукции IL-6, в острой и хронической фазе ин-фекционных и воспалительных процессов разви-вается выраженная гипоцинкемия, обусловлен-ная активным транспортом цинка во внутренние компартменты гепатоцитов и его связыванием внутри клеток металлотионеинами [11, 13,18].…”

“…Поскольку в развитии воспаления и индуктив-ной фазы иммунного реагирования, вследствие общности внутриклеточных путей трансдукции сигнала, выработка IL-1β индуцируется одновре-менно и регулируется сонаправленно продукции IL-6 [10,13,17], изменения выработки IL-1β и IL-6 в условиях меняющейся антигенной или ме-таболической нагрузки, как правило, происходят параллельно и взаимосвязанно [16,18], а IL-1β выступает фактором, индуцирующим продукцию IL-6 [8,11,15], обоснованно полагать, что метал-локомплексы белков γ-глобулиновой фракции могут вовлекаться в регуляцию выработки IL-6, рассматривающегося в качестве основного ци-токина, усиливающего экспрессию генов острой фазы воспаления [11].…”

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

“…All these effects have been identified in experimental animals and humans where an altered zinc status can affect the immunocompetence (Prasad 1998;Haase and Rink 2009b;Mocchegiani et al 2008d). Zinc deficiency coupled with altered immune response, as occurring in ageing, leads to an increased susceptibility for some age-related diseases (Vasto et al 2006;Prasad 2009). As a consequence, several studies suggest the usefulness of a zinc supplementation in the prevention and/or treatment of diseases associated with zinc deficiency (Prasad 2009;Haase and Rink 2009b;Mocchegiani et al 2008d).…”