Consistent with this possibility, TERT down-regulation led to a significant decrease in this protein��s levels. Next, we directly addressed the pro-survival role by knocking down p15INK4B with a shRNA lentiviral vector. This experiment LY2835219 confirmed that low levels of p15INK4B increases the levels of apoptosis in cultured hippocampal neurons. We have here demonstrated that neuronal aging is accompanied by the increased translocation of TERT from the nucleus to the cytoplasm. In hippocampal FTY720 neurons in culture, TERT was exclusively nuclear in the early developmental stages and abundant in the cytosol with time in vitro, especially 2 weeks after synaptogenesis, when metabolic demands are higher. We also observed cytoplasmic TERT in fully differentiated neurons in situ, indicating that TERT nucleus-to-cytoplasm change with age is a normal event in the biology of these cells. The increased levels of TERT in the cytosol of aged neurons may truly relate to a prosurvival need at this stage of life, as its knockdown resulted in higher apoptosis. While it remains to demonstrate that this is also the case in vivo, our results strengthen the recent work by Eitan et al.. These authors found that the over-expression of TERT plays a protective role against oxidative stress in the brain and in motor neurons, delaying the onset and the progression of amyotrophic lateral sclerosis. Second, our work shows that TERT is part of RNA granules in fully differentiated neurons. These RNA granules may well be a type of SGs. In fact, TERT co-precipitates and co-localizes with several components of SGs, including the ?-actin mRNA, P-elF2a, TIA1 and PABP. Moreover, the observation that TIA1 pulls down P-elF2a only in arsenite treated cells and TERT in both, stressed and non-stressed neurons, suggests the existence of two pools of TIA1-TERT complexes, with different composition. In support of this possibility, we could find only one of the two TIA1 mRNA targets in our TERT-IP experiment. Mechanistically, TERT may be part of a type of RNA granules in which mRNAs are sequestered in order to prevent their degradation. This assumption comes from the observation that TERT downregulation results in the reduction of the amount of p15INK4B protein under basal levels of stress. Upon acute stress, TERT dissociates from this mRNA allowing its efficient translation, as demonstrated by qPCR in polysome gradient from stressed neurons. Under the stress condition, release from SGs does not lead to degradation of the p15INK4B mRNA possibly because of its transfer to the translation complex.