鉄欠乏と老化の関連

抄録

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.