Cellular senescence has emerged as a causal factor in obesity-related inflammation and metabolic disorders. Importantly, obesity is associated with shortening of telomere length, which is a major inducer of senescence. However, the question still remains of whether telomere shortening contributes directly to the onset of metabolic disease. To address this question, we have generated a mouse model (p21+/mTert) allowing the conditional expression of telomerase (TERT) that reduced replicative senescence in cells with dysfunctional telomeres in several organs of aged mice. Unexpectedly, we reported that with age p21+/mTert mice became obese, with an increase in fat mass and adipocyte size, and marked signs of liver steatosis. These mice exhibit an increase in food intake, without changes in locomotor activity or energy expenditure. We therefore explored the p21-promoter dependent expression Tert in the hypothalamus (HpT), the major integrating center of incoming metabolic and hormonal signals that controls food intake. We uncover that p21-mTert mice exhibit a clear increase in their hypothalamic progenitor-like pool leading us to hypothesize that Tert expression by modifying the cellular homeostasis in the HpT could modify the central regulation of energy balance and feeding behaviour leading to obesity. The overall objective of THALATEL is to understand how self-renewal properties of neural stem/progenitor cells (Tanycytes) in the central nervous system control hypothalamic neuron function, feeding behaviour, and obesity onset. By combining the expertise of 4 teams with complementary expertise, we will decipher the mechanism by which TERT modifies the hypothalamic neural stem cell (HpT-NSC) niche. We will then characterize the impact of Tert-dependent regulation of HpT-NSC niche activity on energy expenditure and obesity development. Finally, we will address the mechanism by which changing in the hypothalamic HpT-NSC niche affects HpT neuron homeostasis and feeding.