Tightrope act inhibition of mTOR via caloric restriction (CR) or rapamycin induces autophagy. Autophagy clears away damaged proteins and organelles like defective mitochondria, thereby decreasing ROS levels and reducing genomic damage and cellular senescence, thus playing a crucial role in enhancing stem cell longevity. CR may also have a role in maintaining low levels of p16ink4a, a tumor suppressor protein, thus reducing the risk of cancer and promoting proliferation of stem cells. Oncogenesis is countered by loss of PTEN which elicits a p53-dependent prosenescence response to decrease tumorigenesis
