Hematopoiesis, Inflammation and Aging-The Biological Background and Clinical Impact of Anemia and Increased C-Reactive Protein Levels on Elderly Individuals

Abstract

Anemia and systemic signs of inflammation are common in elderly individuals and are associated with decreased survival. The common biological context for these two states is then the hallmarks of aging, i.e., genomic instability, telomere shortening, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. Such aging-associated alterations of hematopoietic stem cells are probably caused by complex mechanisms and depend on both the aging of hematopoietic (stem) cells and on the supporting stromal cells. The function of inflammatory or immunocompetent cells is also altered by aging. The intracellular signaling initiated by soluble proinflammatory mediators (e.g., IL1, IL6 and TNFα) is altered during aging and contributes to the development of both the inhibition of erythropoiesis with anemia as well as to the development of the acute-phase reaction as a systemic sign of inflammation with increased CRP levels. Both anemia and increased CRP levels are associated with decreased overall survival and increased cardiovascular mortality. The handling of elderly patients with inflammation and/or anemia should in our opinion be individualized; all of them should have a limited evaluation with regard to the cause of the abnormalities, but the extent of additional and especially invasive diagnostic evaluation should be based on an overall clinical evaluation and the possible therapeutic consequences.

Keywords: C-reactive protein; aging; anemia; hematopoiesis; inflammation; survival.

Figure 1

The biological hallmarks of aging: an overview and summary of biological characteristics [2,3,4,5,6,7,8,9,10,11].

Figure 2

The bone marrow stem cell niches. The figure gives an overview of important hematopoiesis-regulating members of the various stem cell niches and their main regulatory effects/mechanisms on normal hematopoiesis A detailed discussion of each cell type with corresponding references are given in Section 2.3 (abbreviations: CXCL, C-X-C motif ligand; FGF1, fibroblast growth factor; SCF, stem cell factor; and TGF, transforming growth factor).