Aged HSCs are desensitized to growth-factor stimulation. Age-related changes in young adult and aged HSCs lead to a reduction in Akt signaling, G₁ elongation, and reduced proliferation after growth-factor stimulation. These changes are exaggerated in aged HSCs, which show a delayed G₀ exit. pAkt indicates the phosphorylation and activation of Akt. +++, ++, and + correspond to high, intermediate, and low levels of pAkt, CDK6, and CDK2 protein, as reported in Hammond et al, in freshly isolated HSCs before growth-factor stimulation. G_0, G_1, S, G₂ and M indicate cell cycle phases. S/G₂/M indicates combined duration of S, G₂ and M cell cycle phase.