Anemia in the Elderly: Pathogenesis

描述(由申请人提供)：贫血在老年人中很常见，通常是由于已知的原因，如肾功能衰竭、癌症或慢性感染。但是，即使有已知原因的患者被排除在考虑之外，血红蛋白水平也会随着年龄的增长而下降。我们将研究这些年龄在75岁以上的患者，并比较那些血红蛋白水平在最高十分之一和最低十分之一的患者。年龄在30-40岁之间的患者将作为对照。将对老年患者和对照组进行研究，以寻找红系祖细胞(EPC)衰老的证据和循环红细胞的异常。以外周血粒细胞作为EPC的替代物，检测线粒体DNA、端粒长度和G环结构。红细胞存活率将通过一氧化碳水平和红细胞己糖激酶活性来评估；对红细胞的氧化损伤将通过评估GSSG/GSH、谷胱甘肽过氧化物酶、羰基蛋白、泪水来评估；将记录磷脂酰丝氨酸在红细胞膜上的暴露。将测定血清IL-6和男性血清睾酮水平。显示最高和最低十进制之间差异的参数将是老年人贫血的候选原因。如果这种差异也发生在对照组中，它们可以解释血红蛋白水平的广泛正常变化。

DESCRIPTION (provided by applicant): Anemia is common in the elderly, often as a result of known causes such as renal failure, cancer, or chronic infection. But even when patients with known causes are eliminated from consideration, hemoglobin levels decline during ageing. We will study such patients over the age of 75 and compare those whose with hemoglobin levels in the highest decile with those in the lowest decile. Patients aged 30 to 40 years will serve as controls. The elderly patients and controls will be studied for evidence of erythropoietic progenitor cell (EPC) senescence and for abnormalities of circulating erythrocytes. With circulating granulocytes serving as surrogates for EPC we will examine mtDNA and telomere length and G loop structure. Erythrocyte survival will be estimated by CO levels and red cell hexokinase activity; oxidative damage to erythrocytes will be assessed by estimating GSSG/GSH, glutathione peroxidase, carbonyl proteins, TEARS; exposure of phosphatidylserine on erythrocyte membranes will be documented. Serum IL-6 measurements and in males serum testosterone levels will be determined. Parameters that show differences between the highest and lowest deciles will be candidate causes of anemia in the elderly. If such differences also occur among controls they could account for the broad normal variation in hemoglobin levels.