Rothstein Gerald
Division of Geriatrics, University of Utah School of Medicine, Salt Lake City 84132, USA.
J Am Geriatr Soc. 2003 Mar;51(3 Suppl):S22-6. doi: 10.1046/j.1532-5415.51.3s.3.x.
Normal hematopoiesis constitutes the process of producing diverse, differentiated blood cell types in a manner related to physiological requirement. During aging, modulation of hematopoiesis becomes disordered, impairing the ability of older people to respond appropriately to the physiological demand for blood cell replacement triggered by stimuli such as blood loss or cytoreductive chemotherapy. This may contribute to the increase in the prevalence of anemia that is observed during aging. In addition, various age-related events, such as genomic mutations secondary to oxidative stress and impaired regulation of cytokine production, may contribute to or cause the emergence of abnormal clones of hematopoietic cells. Therefore, normal hematopoiesis is disrupted, and the hematopoietic system is populated with cells that are quantitatively and functionally deficient and are also subject to leukemic transformation. These defects in the production and maturation of the various differentiated blood cells are referred to as myelodysplastic syndromes. These syndromes are so tightly associated with aging that they are considered to be geriatric disorders; they can lead to anemia, neutropenia, and thrombocytopenia and to the development of acute nonlymphoblastic leukemia. Dysregulation of mechanisms controlling hematopoiesis is therefore an important characteristic of the hematopoietic system in the elderly, but the response of progenitor cells to humoral stimulators is preserved and accounts for the effectiveness of recombinant hematopoietic growth factors used as emerging treatment modalities for hematopoietic disorders in the elderly.
正常造血是一个以与生理需求相关的方式产生多种分化血细胞类型的过程。在衰老过程中，造血调节变得紊乱，损害了老年人对失血或细胞减灭性化疗等刺激引发的血细胞替代生理需求做出适当反应的能力。这可能导致衰老过程中观察到的贫血患病率增加。此外，各种与年龄相关的事件，如氧化应激继发的基因组突变和细胞因子产生调节受损，可能促成或导致造血细胞异常克隆的出现。因此，正常造血受到破坏，造血系统中充斥着数量和功能上有缺陷且易发生白血病转化的细胞。各种分化血细胞的产生和成熟中的这些缺陷被称为骨髓增生异常综合征。这些综合征与衰老密切相关，以至于被认为是老年疾病；它们可导致贫血、中性粒细胞减少和血小板减少，并导致急性非淋巴细胞白血病的发生。因此，控制造血机制的失调是老年人造血系统的一个重要特征，但祖细胞对体液刺激物的反应得以保留，这解释了作为老年人造血疾病新兴治疗方式的重组造血生长因子的有效性。
