Copper(Cu)is related intimately to oxygen stress and its detoxication, that is prooxidant and antioxidant. Oxygen stress can make aging process accelerate. Therefore it is important to clarify the relationship between Cu metabolism and aging. The amounts of body Cu are the following orders of bone > muscle > liver > brain. The absorption of dietary Cu is carried out mainly in the proximal portion of small intestine. After absorption Cu is transferred to the target proteins and organelles by both transporters and chaperones of Cu. By gene deficit severe hypocupremia occurs in patients with Wilson disease or with Menkes disease, resulting in some prominent features of Cu deficiency. Cu proteins play a pivotal role in cellular metabolism through enzyme activities and in ameliorating oxygen stress. During 6 years from 1997 to 2002 Cu-poor enteral liquid foods were used in elderly inpatients with cerebrovascular disease, resulting in severe hypocupremia after about 6 months. Then Cu-rich ones were recently administered to inpatients, resulting in normocupremia from hypocupremia after about 4 months. The administration of L-8 enteral liquid food(Asahi-kasei Pharma)could maintain in the normal range of serum Cu and ceruloplasmin(Cp)during 21 months, which contained 0.8 mg of Cu per 1,000 kcal and might be fulfilled with adequate intakes of Cu. In elderly inpatients with extremely low levels of serum Cu below 10 µg/dl(normal range 70 - 132 µg/dl)leucopenia, neutropenia and anemia were detected, which could be improved by Cu supplementation. By bone biopsy and aspiration in one woman aged 45 years, increments of both myelocytes and erythroid cells are found, indicating a disturbance of maturity, of which cytoplasma involves vacuole degeneration. In clinical investigations of both sexes normocupremia was obtained from hypocupremia by enteral liquid foods with mean 0.69 mg of daily Cu intake, and with 0.8 mg of daily Cu for 24 months. Normocupremia was maintained during 21 months, when male elderly inpatients received mean 0.96 mg of Cu intake and female ones did mean 0.8 mg of Cu intake. Therefore, an adequate Cu intake can be estimated to be 0.69 mg to 0.96mg daily in elderly inpatients with tube feeding, corresponding with 0.7 mg to 0.8 mg of Cu recommendation of Japan in 2005. About inflammation serum Cu and Cp levels are parallel to serum CRP. The length of lifespan from beginning of tube feedings was longer significantly in female elderly inpatients with normocupremia as compared to female ones with hypocupremia, indicating a novel antiaging effect of normocupremia due to adequate Cu intake.

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Selenium is an essential trace element and 25 selenoproteins, which contain the element in the form of selenocysteine, have been characterized in mammals. Selenium exerts its biological activity largely through these selenoproteins. However, some selenium compounds, such as selenite, Se-methylselenocysteine, methylseleninic acid, and selenomethionine, also have biological effects. Several studies indicate that these selenium compounds are among the most promising agents for cancer chemoprevention and anti-aging. A large chemoprevention study has been carried out using selenomethionine, because selenomethionine was thought to be an appropriate form of selenium supplementation for human nutritional. However, a randomized controlled trial shows that selenium-rich yeast (containing selenomethionine) may increase the risk for type-2 diabetes. The study of the chronic effects of selenium compounds including selenomethionine for usage in long-term supplementation is needed.

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Iron deficiency is the most prominent nutritional disease in the world today. In this review, a conspectus of iron deficiency is outlined and the significance of iron deficiency as a possible promoter of senescence is discussed. Diets poor in bioavailable iron (heme iron in red meat) and rich in iron absorption inhibitors (tannin or condensed and polymerized polyphenols in tea and phytate in bran) and excessive menstrual blood loss are the major causes of iron deficiency. Iron deficiency is frequently associated with zinc and other nutritional deficiencies. Both iron deficiency without anemia and iron deficiency anemia decrease functional iron in tissues that leads to decreased maximal oxygen consumption, delayed mental development and decreased cognitive function. Iron deficiency induces mitochondrial decay that impairs energy and lipid metabolism and decreases antioxidant capacity via diminished hemoglobin, catalase activity, NADPH supply and bilirubin production. Iron deficiency also induces copper and manganese accumulation in tissues. Free copper ion is the potent prooxidant that facilitates production of reactive oxygen species via Fenton reaction and Haber-Weiss reaction. Copper is accumulated in liver of iron-deficient rats. Iron deficiency may contribute to the pathogenesis of copper associated childhood cirrhosis in humans. Manganese, a potent Parkinsonism-evoking agent, is accumulated in brain of iron-deficient rats, probably via upregulated DMT1 expression. It is well known that iron deficiency is the most important risk factor of restless legs syndrome in humans, a sensory motor dysfunction that occasionally associates Parkinsonism. Functional iron deficiency is the pathophysiological condition where a shortage of iron supply to the erythroid marrows exists compared to their iron demand, excluding dietary iron deprivation and blood loss. Functional iron deficiency sometimes associates tissue iron deposition that may cause chronic diseases including myocardial infarction, cancers and type 2 diabetes mellitus, since free ferrous ion is the potent prooxidant like free copper ion. Overall, iron deficiency might promote senescence in humans.

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This paper summarizes the authors' recent work on trace elements (TEs) in the Chinese medicinal herbs (CMHs) and hot springs from Hainan Island, China. The review encompasses: (a) distribution features of TEs in four CMHs and their decoctions, (b) modulation and control of the distribution modes of TEs in water decoctions, (c) analysis of CMHs for mercury and its removal from water decoctions and (d) contents of minerals and trace elements in two tropical hot springs in Hainan Island. We illustrate contents and distribution features of trace elements in medicinal materials and their decoctions of four CMHs (Areca Seed, Villous Amomum Fruit, Morinda Root, and Sharpleaf Galangal Fruit) and two hot springs. We describe a novel method for optimizing the decocting technology from the aspect of trace elements, which is expected to control the quality of decoctions. In addition, we present briefly two methods for the Hg removal from decoctions of CMHs.

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Wilson's disease (WD) is an autosomal recessive copper transport disorder characterized by the accumulation of intracellular copper in the liver and extrahepatic issues. Toxic accumulation of copper causes tissue damage, mainly in the liver and brain. WD is caused by a large number of mutations in the ATP7B gene. Some of the mutations appear to be population specific, whereas others are found in patients from a variety of different ethnic background. The H1069Q mutation is the most common mutation in European and North American patients with WD, while R778L mutation is found in most Asian patients. Our study showed that there were no significant differences in three clinical features (mean age at onset, number of patients with hepatic symptoms, and number of patients with neurologic symptoms) between Asian homozygotes and heterozygotes for R778L. Moreover, our study revealed that no association was found between ApoE ε3/3 genotype and WD clinical presentation in Chinese R778L homozygous, although the high frequency of ApoE ε3/3 in those Chinese R778L homozygous with WD was not significantly different from that in healthy controls. Therefore, there was different pathological presentation between Asian and Caucasian patients. WD is a treatable disease. In 2002 we have reported the efficacy of long-term (3-18 years) treatment with high-dose zinc sulphate in Chinese WD children. In the beginning of 2008 zinc acetate has been approved by the Ministry of Health, Labour and Welfare of Japan for therapy of WD patients because it do not have serious side effect. Our observations also revealed that abnormal copper levels in the liver of WD may be associated with the development of hepatocellular carcinoma. WD patients should be screened for hepatocellular carcinoma.

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Hydrofluoric acid (HFA) is used widely in many industrial processes. There have been many reports on the acute lethal effects of HFA in relation to occupational accidents. This study was designed to investigate the time-dependent harmful effects after exposure of sub-toxic doses. The serum fluoride ion (F) kinetics is also considered in the discussion of the relationship between the concentrations of serum HFA and the disorders. Rats were intravenously injected with HFA (1.6 or 9.6 mg/kg body weight) for the dose-response relationship study. For each dose, the rats were assigned to one of seven groups. Blood samples of the 0-min group were obtained from the carotid artery prior to injection as control. The other six groups were classified according to sampling times (5, 10, 30, 60, 120 and 300-min) for the time-dependent study. The 1.6 mg/kg dose decreased the ionized calcium (Ca²⁺) level significantly after 30 min, and it also decreased total calcium (Ca) level after 300 min. The 9.6 mg/kg dose rapidly worsened renal dysfunction after 60 min. It increased the serum potassium level after 60 and 120 min and it decreased Ca and Ca²⁺ levels until 300 min. Although the respiratory compensation functioned, the base excess and HCO₃ ^- level and did not completely recover after 300 min. F concentration rapidly increased in the 5-, 10-, 30- and 60-min group, and it showed no apparent differences in the 120- and 300-min groups compared with the control. Because kidney is a target organ of F, renal dysfunction could be caused by even sub-toxic dose. Although the serum concentration of HFA was diminished, the electrolyte abnormalities and metabolic acidosis would be prolonged, because trace of F could activate K channels and fluorapatite formation for several hours.

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Dietary intakes of alkaline metals (Na, K, Rb, and Cs), alkaline earths (Ca, Mg, Sr, and Ba) and phosphorus (P) in Ukrainian subjects were estimated in relation to the health effects on residents after the Chernobyl accident. Two hundred and sixty-eight diet samples were collected from 25 oblasts (regions) using a duplicate portion method. The elements were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) or inductively coupled plasma mass spectrometry (ICP-MS). For Ukrainians, median daily intakes per person were as follows: Na 4.08 g; K 2.89 g; Rb 2.19 mg; Cs 3.78 μg; Ca 0.696 g; Mg 0.254 g; Sr 1.88 mg; Ba 0.507 mg; and P 0.991 g. The intakes of Na, K, Ca, and Mg were almost the same as worldwide reported values, while those of Sr and Ba were higher and Cs and P were lower than those values.

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Toxicity and oxidative stress of organic and inorganic selenium to rats was studied by orally administering them daily with sub-median lethal dose (3.2mg Se/kg body weight, 0.25-1.0 times of LD₅₀). Four groups of rats were respectively administered with water (A), aqueous suspension of selenium enriched yeast (B), sodium selenite solution suspended with baker's yeast (C), and aqueous selenite solution (D) for 38 days. Body weights of the rats were measured every day, and oxidative stresses of blood plasma, once a week during the survey by d-ROMs test (derivatives of Reactive Oxygen Metabolites), and plasma biochemical tests and Se deposition to serum and liver, at autopsy. Body weights of B-D groups decreased after a day of first administration, turned to increase after a week. The growth rates, however, were 0.4, 0.4, and 0.1 times the rate of A, for B, C, and D, respectively. The amounts of Se depositions were 9(B) and 5(C) times the value of D in serum, 2.1(B) and 1.4(C) times the value of D in liver, much larger differences between organic and inorganic Se than those reported for low concentrations of Se supplementation. ALT and AST activities in plasma were almost the same for A and B, but 2 and 5 times larger for C and D, suggesting that Se yeast has a little effect on the function of liver, but Na₂SeO₃ caused hepatic lesion. D showed malnutrition with low total protein and albumin content in their bloods. The d-ROMs value of A remained constant (280) but those of B-D increased with days reached a plateau (850) after 4-5 weeks, showing rapidly increasing oxidative stress with days. No differences in d-ROMs values existed with time among B-D despite the difference in toxicity between B and D.

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