Research Paper Volume 5, Issue 8 pp 623—636

Figure 7. Schematic presentation of key pathways associated with cellular senescence and aging linking mTOR- and DNA damage- signaling.

The ongoing translation particularly during perturbed cell cycle progression (replication stress), is considered to be the major factor leading to senescence. Suppression of translation that may have anti-aging effect can be achieved at several steps along the mTOR signaling pathway (marked A-g), as discussed in the text. Activation of autophagy provides an additional gero-suppressive effect. The translation requires production of ATP and thus generates ROS that cause oxidative DNA damage, which when occurs at sites of oncogenes and tumor suppressor genes, may lead to neoplasia. The damage of telomeric DNA and lipid peroxidation by ROS further contributes to the senescent phenotype. The in vitro model of stress-induced cellular senescence as presently described can be used to evaluate potential gero-suppressive agents in terms of their effect in reduction of mTOR/S6- and DNA- damage signaling. See text for further details.