Hematopoietic stem cells (HSCs) sustain production of all blood cells through the lifetime. However,

HSCs gradually lose their regenerative potential during aging. The project will check whether bone

marrow (BM) niche drives age-related disturbances among HSCs. Proposed experiments will verify

if the changes in the niche acquired during aging contribute to decline in function of HSC in elderly

individuals. We will verify the possible mechanism of HSC-niche interactions during aging. Our

preliminary data suggests that Neogenin-1 (Neo-1)/Netrin-1 (Ntn-1) axis may be implicated in

niche-driven aging of HSC. To verify our hypothesis we proposed approach based on new

transgenic mouse models. Finally, we check whether Neo-1 defines the aging fraction of human

HSCs and whether Ntn-1 is conserved among human BM niche. The project will contribute to

understanding how bone-marrow niche regulates aging of HSCs and how this knowledge can be

translated to clinical application.