ABSTRACT
It is known that metallothionein (MT) mRNA expression first increases with age, but then decreases again in the very elderly. Here we report that MT protein levels also decrease in very old age, and that this is independent of dietary zinc intake. Age-related changes of MT, as well as alterations of zinc homeostasis (intracellular labile zinc and NO-induced zinc release), occur both in human PBMCs ex vivo and also in CD4+ T cell clones progressing through their finite life span in vitro. These results suggest that phenomena observed in very old people can be at least partially attributed to diminished cell proliferation.
Subject(s)
Aging/metabolism , Cellular Senescence , Down-Regulation , Metallothionein/metabolism , Aged , Aged, 80 and over , CD4-Positive T-Lymphocytes/metabolism , Clone Cells , Female , Humans , Male , Middle AgedABSTRACT
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.
Subject(s)
Dietary Supplements , Gene Expression Regulation/drug effects , Immunity, Innate/drug effects , Longevity/drug effects , Metallothionein/biosynthesis , Zinc/pharmacology , Animals , Antioxidants/metabolism , Clusterin/immunology , Clusterin/metabolism , Gene Expression Regulation/physiology , Homeostasis/drug effects , Homeostasis/physiology , Humans , Immunity, Innate/physiology , Interleukin-6/biosynthesis , Interleukin-6/immunology , Longevity/physiology , Lymphocytes/immunology , Lymphocytes/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Superoxide Dismutase/metabolism , Zinc/immunology , Zinc/metabolismABSTRACT
The paper shows the results on the relationship between zinc status, psychological dimensions (cognitive functions, mood, perceived stress) and nutritional aspects in European healthy old subjects recruited for ZINCAGE Project (supported by the European Commission in the Sixth Framework Programme). The old healthy subjects were recruited in Italy, Greece, Germany, France, Poland taking into account the different dietary habits between Northern and Southern European Countries and the pivotal role played by zinc for psychological functions. Measures of the cognitive status, mood and perceived stress level were obtained at baseline, using the "Mini Mental State Examination (MMSE)"; the "Geriatric Depression Scale (GDS - 15 items)" and the "Perceived Stress Scale (PSS)", respectively. Nutritional status was assessed using "Frequency Food Questionnaire". The sample included 853 old subjects, classified in 4 groups of age: 60-69-years-old (n = 359); 70-74-years-old (n = 225); 75-79-years-old (n = 153); 80-84-years-old (n = 116). Subjects were studied on the basis of plasma zinc, in which zinc
