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The role of age-associated endothelial dysfunction in hematopoiesis


Increase in life expectancy has been associated with high risk of development of age-associated diseases. Anemia and endothelial dysfunction are a common finding in the elderly and can lead to serious conditions such as heart failure. The causes of anemia in the elderly are multifactorial and commonly associate to micronutrient and/or macronutrient insufficiency. Endothelial cells play important function in the control of the hematopoiesis process, providing essential regulatory signals for maintenance, proliferation and differentiation of blood cells throughout life. For a long time stem cells have been considered self-renewing and therefore exempt from the adverse effects of the aging processo However, this assumption is currently found unacceptable. Although there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, new data strongly suggest that even the most primitive stem cell exhibit a certain degree of aging. Little is known regarding the mechanisms that drive age - associated hematopoietic dysfunction. The bone marrow microenvironment has been shown to be essential for maintenance of the hematopoietic niche and cellular function. Any alterations in this microenvironment such as inflammation and malnutrition can have an impact and limit hematopoietic function directly or indirectly. Accordingly, this proposal aims to address important questions related to hematopoietic dysfunction and investigate novel mechanisms involved in the control of vascular aging and its contribution to hematopoietic homeostasis. (AU)

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