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Polymerase-1 over-activation causes cell death in the senile brain. [1] NAD+ as the substrate for poly ADP-ribose polymerase (PARP) may be depleted and causes energy depletion in mitochondrial, especially in the senile brain. [2] PAR may directly cause the release of apoptosis inducing factor (AIF) from mitochondrial and transport into the nucleus, thus promoting macrophage migration inhibitory factor (MIF) to translocate from the cytoplasm to the nucleus and cause DNA fragmentation.
