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Stress Strains Stem Cells

Hematopoietic stem cells (HSCs) are responsible for the lifelong production of blood cells. The accumulation of DNA damage in HSCs is a hallmark of aging and is a likely major contributing factor in age-related tissue degeneration and cancers.  Michael Milsom, from Heidelberg Institute for Stem Cell Technology and Experimental Medicine gGmbH (Germany), and colleagues have observed that the increased energy demands of the stem cells during stress result in elevated production of reactive metabolites that can directly damage DNA. When this occurs concurrently to the cell’s DNA replication process, the stem cell may die or acquire mutations that may cause cancer.  The team then utilized a mouse model of Fanconi anemia, finding that the stress response causes bone marrow hematopietic stem cells to be severely depleted. The study authors submit that:  “Our findings establish a novel link between physiological stress and DNA damage in normal [hematopoietic stem cells] and provide a mechanistic explanation for the universal accumulation of DNA damage in [hematopoietic stem cells] during ageing and the accelerated failure of the haematopoietic system in Fanconi anaemia patients.”

Walter D, Lier A, Geiselhart A, Thalheimer FB, Huntscha S, Sobotta MC, Milsom MD, et al.  “Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells.”  Nature. 2015 Feb 18.

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