SIRT1 and neoplasm: For example, in the context of regulating intertwining networks, p53 seems to participate in life extension as a downstream activator for apoptosis in the well-known IGF1/mTOR pathway, suppressing tumor development; but its continuous increase in older life may overwhelm SHP's binding to miR-34a and become the dominant activator for miR-34a, resulting in the SIRT1 loss described above.