Aging is an inevitable process that is influenced by genetics, lifestyle and the environment. However, the underlying mechanisms of the aging process are not fully understood. Aging has been shown to be closely associated with an increase in pro-inflammatory cytokines. Iron is an important micronutrient that plays a vital role in the body. The daily requirement for dietary iron is approximately 1 mg for males and 2-3 mg for adolescents and females. Iron intake is about 15 mg/day in the diet and only 5-10% of this amount is absorbed in the intestine. Iron deficiency anemia is caused by problems in the synthesis of hemoglobin. The diagnosis of iron deficiency anemia comes from hemoglobin values that are less than 11.5 g% in women and less than 13.5 in men. This case is quite common all over the world.
Being elderly is a risk factor for the development of iron anemia due to drug intake, changes in appetite and intestinal malabsorption. Cytokines play an important role in regulating the inflammatory response. The reason for the increased frequency of anemia in old age may be the dysregulation of inflammatory markers with aging. It has been suggested that an increase in direct or indirect pro-inflammatory cytokines (CRP, TNF-α, IL-6 etc.) inhibits erythropoietin and thus may lead to anemia. Furthermore, antimicrobial peptides (AMPs) and proteins play an important role in human immune defense. AMPs are key elements of innate immunity and wound healing. Defensins, hepcidin and chemerin are some of the antimicrobial proteins.
Hepcidin is a recently discovered hormone that is synthesized in the liver and is an antimicrobial protein that exhibits antibacterial and antifungal properties by maintaining the iron balance in the microorganism thus regulating its metabolism. The structure of hepcidin is designed to bind iron atoms in a stable, non-releasable form, a process called chelation. When iron stores are adequate, hepicidin production increases in the liver and erythropoietic signals lead to a reduction in its synthesis. Therefore, it may regulate the way iron is transported from plasma enterocytes in the small intestine. During anemia, hepcidin creates an important link between the body’s defenses, inflammation and iron metabolism, apart from the physiological bone marrow impairment due to age.
Other defensive peptides such as chemerin and defensin-beta are also antimicrobial and working by seizing the iron necessary for bacterial growth, they can over time deplete our internal stocks and lead to chronic anemia. In fact, this is the most likely mechanism that scientists believe is responsible for the onset of anemia in chronic inflammatory conditions. Intestinal disorders such as Crohn’s disease, ulcerative colitis and celiac disease are among the medical conditions most commonly associated with chronic anemia. Traditionally, anemia secondary to these pathologies was thought to derive from intestinal malabsorption due to mucosal erosion. It is only for almost twenty years that the role of hepcidin and similar peptides has emerged as responsible or a competitor to the appearance of chronic anemia in many clinical conditions.
The first publications demonstrating a role of inflammatory cytokines in causing iron deficiency anemia date back to the beginning of 2000, a phenomenon that is evident in the elderly with chronic pathologies such as osteoarthritis, diabetes, chronic bronchopathy, to name the most common. The problem becomes more evident, then, during particular medical-clinical conditions. Pathologies such as chronic renal disease (CKD), bed rest syndromes, after-effects of cerebral stroke and poorly managed diabetes (including complications) have in common a prolonged inflammatory process, but with the aggravating circumstance of being slow and often sub-clinical, which becomes exhausting for the body. Not least are all the conditions of chronic infection of surgical wounds or prostheses, which are routinely encountered in the healthcare sector.
Considering the average age of over 70 years of those undergoing hip or knee replacement for degenerative arthrosis, the concomitant accompaniment of other chronic conditions (including hypertension and diabetes cover 70% of cases) and disturbances of circadian rhythms and appetite that accompany hospitalization and bed rest, it is no wonder that most patients with prosthetic surgery respond slowly to iron therapy for recovery of the haematological picture. It is also not infrequent that upon suspension of external supplementation with iron, the hematological picture returns slowly to fall again and that it becomes necessary to transfuse blood or concentrated red blood cells. This condition is particularly evident in those suffering from CKD, where erythropoietin is used, the hormone produced by the kidneys that stimulates the construction of red blood cells.
The continuous production of cytokines due to these pathologies stimulates the production of hepatic hepcidin, just like there was a chronic infection despite this being absent. And the depletion of internal iron stores leads the body to develop anemia as well as exhaustion, respiratory fatigue and other symptoms. Don’t forget, in fact, that muscles also have their hemoglobin (which is called myoglobin) and that like this it contains iron. Getting older certainly has its downsides, and accumulating more morbidity doesn’t set good ground. Reversing aging is impossible and the abuses committed by young people are paid for by adults. For which a suitable, healthy and active lifestyle, with occasional exceptions, is the right thing to maintain in order to age well and/or in health.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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