Learning Objectives:

1 The quiescent status of hematopoietic stem cells (HSCs), long considered to be strictly protective, has a dark side as it forces HSCs to use error prone DNA repair mechanisms and accumulate mutations.

2 Loss of Sirtuin 7 in aged HSCs leads to protein folding stress in the mitochondria; restoring youthful levels of Sirtuin 7 can rejuvenate aged HSCs.

3 Mesenchymal stromal cells in the HSC bone marrow niche regulate local IGF-1 signaling; the reduction of which reduces fibrosis and myelopoiesis and may increase lifespan.