Hepcidin and the pathogenesis of anemia in older adults.

描述(由申请人提供)：贫血在老年人中很常见，并与一系列不良后果有关，包括生活质量下降、虚弱、疲劳、残疾和死亡率增加。老年人的贫血是由肾功能衰竭、慢性炎症和营养不足引起的，大约三分之一的贫血是无法解释的。海普西丁是一种新近发现的多肽激素，可能是炎症性贫血的主要调节剂。海普西丁似乎是铁代谢的主要调节剂，并在铁充足状态、铁超载和炎症的情况下上调。海普西丁在老年人贫血中的作用尚未得到很好的描述。低度促炎状态在老年人中很常见，但目前尚不清楚这种状态是否会导致海普西丁上调并导致贫血。我们假设：(I)老年人的低级别促炎状态，即使在没有临床明显疾病的情况下，也可以通过海普西丁的上调而导致贫血，(Ii)不明原因的贫血以尿海普西丁水平高为特征，以及(Iii)在登记时尿海普西汀水平升高的老年人保持贫血或发展为贫血的风险更高。我们的具体目标是确定不同形式的贫血的特征，包括老年人贫血的重叠原因，研究促炎状态和海普西丁上调之间的关系，描述老年人不同形式贫血中血红蛋白、海普西丁、营养状况、炎症和激素状态之间的关系，确定与贫血风险增加相关的预测因素(临床和生物标志物，包括海普西丁)，以及表征海普西丁与血红蛋白和炎症相关的纵向变化。为了解决这些目标，我们将在正在进行的NIH资助的INCHIANTI研究中测量尿庚西丁水平，这是一项基于人群的前瞻性老龄化流行病学研究，在意大利基安蒂红酒地区(托斯卡纳)对1,453名男性和女性进行。这些受试者最初是在1998-2000年间招募的，每三年一次，直到2007-2009年。这项研究包括一个丰富的数据库，与炎症、贫血、营养、激素和体能、慢性病、残疾和死亡率有关。这项研究应该为老年人贫血的流行病学和生物学机制提供新的见解，并有助于确定旨在预防和治疗贫血的战略。

DESCRIPTION (provided by applicant): Anemia is common in older adults and is associated with a wide spectrum of adverse outcomes, including reduced quality of life, weakness, fatigue, disability, and increased mortality. Anemia among older adults is caused by renal failure, chronic inflammation, and nutritional deficiencies, and about one-third of the anemia is unexplained. Hepcidin, a recently discovered peptide hormone, may be a major modulator in the anemia of inflammation. Hepcidin appears to be the principal regulator of iron metabolism and is upregulated by an iron-replete state, iron overload, and inflammation. The role of hepcidin in anemia among older adults has not been well characterized. A low grade proinflammatory state is common in older adults, but it is unclear if this state can lead to the upregulation of hepcidin and contribute to anemia. We hypothesize that (i) the low grade proinflammatory state in older adults, even in the absence of clinically apparent disease, can cause anemia through the upregulation of hepcidin, (ii) unexplained anemia is characterized by high urinary hepcidin levels, and (iii) older adults with elevated urinary hepcidin levels at enrollment are at higher risk of remaining anemic or developing anemia. Our specific aims are to characterize different forms of anemia, including overlapping causes of anemia, in older adults, to study the relationship between the proinflammatory state and upregulation of hepcidin, to characterize the relationships between hemoglobin, hepcidin, nutritional status, inflammation, and hormonal status in the different forms of anemia among older adults, to identify predictors (clinical and biological markers, including hepcidin) that are associated with an increased risk of developing anemia, and to characterize longitudinal changes in hepcidin in relation to hemoglobin and inflammation. To address these aims we will measure urinary hepcidin levels in the ongoing NIH-funded InCHIANTI study, a population-based, prospective epidemiological study of aging conducted among 1453 men and women in the Chianti area (Tuscany) of Italy. The subjects were originally recruited in 1998-2000 and are seen every three years until 2007-2009. The study includes a rich database related to inflammation, anemia, nutrition, hormones, and physical performance, chronic disease, disability, and mortality. This study should provide new insight into the epidemiology and biological mechanisms of anemia among older adults and help identify strategies aimed at the prevention and treatment of anemia.