Chronic inflammation is a feature of aging, driven by mechanisms such as an increased burden of senescent cells and overactivation of the innate immune system in response to cellular stress. Researchers here present data to suggest that chronic inflammation contributes to age-related anemia, a reduced production of red blood cells that perhaps occurs via an indirect disruption of iron metabolism by inflammatory signaling, and that in turn lowers the available levels of iron needed for the creation of red blood cells.
Anemia is a common hematological disorder that affects 17% of persons older than 65 years. The World Health Organization (WHO) defines anemia as a decreased number of erythrocytes and/or decreased hemoglobin (Hb) levels of less than 12.0 g/dL in women and 13.0 g/dL in men. In older adults, anemia can be divided into nutritional deficiency anemia, bleeding anemia, and unexplained anemia that might be caused by the reduced erythropoietin (EPO) activity, the progressive erythropoietin resistance of bone marrow erythroid progenitors and the chronic subclinical pro-inflammatory state. Overall, one-third of older patients with anemia have a nutritional deficiency which mainly includes iron, folate or vitamin B12 deficiency, one-third have a chronic subclinical pro-inflammatory state and a chronic kidney disease, and one-third suffer from anemia of an unknown cause.
Understanding the pathophysiology of anemia in this population is crucial because it contributes to frailty syndrome and falls, cognitive decline, depression, functional ability deterioration, and early mortality. A prospective cohort analysis of 3758 patients aged 65 years and older showed that a new-onset anemia was associated with an increased mortality risk with a drop in Hb of 1 g/dL.
The pro-inflammatory state in older age, called inflammaging, is manifested by the release of a large number of inflammatory mediators that are produced to repair damage at the tissue level. Inflammaging is a result of changes in the immune system also known as immunosenescence. The inflammatory molecules produce adverse effects on the cells of the hematological system, and these include iron deficiency, reduced EPO production and elevated phagocytosis of erythrocytes by hepatic and splenic macrophages, and also enhanced eryptosis by oxidative stress in the circulation.
In this study, low Hb concentration was observed to be associated with subclinical, chronic inflammation, exhibited by high levels of IL-1β and TNFα. In the large InCHIANTI study, the unexplained anemia cohort (36% of all the anemic population) was found to have higher levels of pro-inflammatory markers and higher resistance of bone marrow erythroid progenitors to erythropoietin compared to non-anemic controls. The mechanisms underlying low Hb levels in older adults are multifactorial and complex. Our study suggested that the underlying mechanisms involve subclinical chronic low-grade inflammation, bone marrow resistance to EPO, and changes in hepcidin levels, ultimately affecting iron metabolism and resulting in lower serum iron levels.
Link: https://doi.org/10.3390/ijms24108944
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