Research Perspective Volume 2, Issue 11 pp 875—883
A novel insight into aging: are there pluripotent very small embryonic-like stem cells (VSELs) in adult tissues overtime depleted in an Igf-1-dependent manner?
Figure 3. Insulin/Igf signaling and imprinted genes. In mammals there are three insulin factors (Insulin, Igf-1, and Igf2) that bind to two tyrosine kinase receptors, insulin receptor (InsR) and Igf-1 receptor (Igf-1R). Igf2R is a non-signaling mannose-type sink receptor for Igf2. Activation of InsR and Igf-1R lead, depending on cell type, to metabolic and proliferative responses. RasGRF1 is a small GTP exchange factor (GEF) that is involved in signaling from InsR and Igf-1R. VSELs show a decrease in Igf2 and RasGRF1 expression (blue) and overexpression of Igf2R (red) due to changes in the epigenetic state of imprinted genes. These epigenetic changes in genes regulating Insulin/Igf signaling keep VSELs quiescent in adult tissues. We hypothesize that chronic exposure to Igf/Insulin accelerates premature depletion of VSELs.