Figure 2

Diagrammatic illustration of potential factors that feed into the bone marrow-derived mesenchymal stem cell (BM-MSC) niche. Diminished BM-MSC function associated with natural aging may be due to deleterious changes at the niche level. Different factors that regulate and maintain the local BM-MSC microenvironment are depicted. Within the niche, BM-MSCs are responsive to metabolic factors and their products, such as oxidative stress and reactive oxygen species (ROS). Paracrine and signaling factors such as Notch, transforming growth factor (TGF)-β, mitogen-activated protein kinase (MAPK), Wnt and NF-ĸB are known to be age dysregulated in the stem cell niche. Physical and environmental factors such as space constraints, and cell-cell interactions between BM-MSCs and other stem and non-stem cells resident in the bone marrow, and between BM-MSCs and the local extracellular matrix may undergo age-associated changes. In response to these changes, BM-MSCs are likely to undergo molecular level changes, such as increased levels of pro-aging factors, DNA damage, telomerase attrition and transcription factor changes. The direct consequence of these changes is diminished BM-MSC function, self-renewal and differentiation capacity. ECM, extracellular matrix; HSC, hematopoietic stem cell.