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Two papers in the June 7 issue of Nature strengthen the connection between DNA damage and exhaustion of blood (haematopoietic) stem cells as we age. Nijnik et al1 used a genetic approach, studying a mouse mutant with a defect in DNA repair enzyme called LIG4. Because this enzyme is exquisitely suited for joining ends of DNA and nothing more, the scientists could be sure that any abnormalities they observed in the mouse's stem cells resulted from accumulation of double stranded DNA breaks. They found that the mutant mice possessed far fewer haematopoietic stem cells than wild type mice, and that this was the result of less self renewal. In a separate study, Rossi et al2 confirmed that DNA damage could contribute to stem cell decline with age under conditions of stress, and three genomic maintenance pathways, nucleotide excision repair, telomere maintenance, and non-homologous end-joining, prevented this decline. They also found that in the haematopoietic stem cells of old mice, there is an increase in a particular histone phosphorylation that reveals the presence of DNA damage. This gap between young and old mice closed at later stages of differentiation, suggesting that it is the stem cells that are most sensitive to DNA damage, and that more mature progenitor cells are better able to repair their DNA in old mice. Together the two papers suggest that repair of DNA double-strand breaks is a rate limiting step for haematopoietic stem cells, and that conditions that increase oxidative DNA damage may profoundly influence tissue ageing and repair after injury.