Figure 1.

Intracellular factors affecting compensatory regeneration in aged livers. Young livers (left): reduction of the liver mass after PH leads to YAP/Sirtuin-dependent transcription of BubR1. BubR1, in turn, induces the cell adhesion protein DISC1 which provides the proper microstructural adaptation during regeneration. Aged livers (right): the increased levels of MSTs counteract YAP activation. Furthermore, as aging is associated to decreased SIRT-1 expression, there is a reduction of the YAP/Sirtuin-dependent transcription of BubR1. This lead to reduction of DSC1 expression, weakened microstructural adaptation and upregulation of p21. As a result, G1 cell cycle arrest and impairment of liver regeneration is observed.