The cyclin-dependent kinase 4 (CDK4) is a protein well known in many cellular processes such as proliferation, differentiation and metabolism. A dysregulation of this protein expression can be implicated in pathological contexts like cancers. In the brain, the role of CDK4 has been less well known. In these last ten years, some studies started to explore its implication in adult neurogenesis and neurodegenerative diseases. Preliminary data obtained by our group showed that CDK4 is mainly expressed by glial cells such as oligodendrocytes and astrocytes in the brain area named hypothalamus. The hypothalamus of mice deleted for CDK4 (CDK4 KO mice) presented less myelin content as well as an increase in expression of senescence-associated secretory phenotype markers (SASP). Interestingly it is already described that aberrant senescence of astrocytes can induce a decrease of the content of brain myelin. In addition, it has been shown that CDK4 inhibitors induced cellular senescence in human fibroblasts. Altogether, we hypothesized that CDK4 deletion could induce senescence, particularly in hypothalamic astrocytes but also in brain areas other than the hypothalamus. We used primary cultures of hypothalamic astrocytes from Cdk4flox/flox mice treated with TAT-CRE or TAT-FITC (control group) to study the effect of CDK4 deletion on astrocytes senescence. We also studied the expression of genes coding for SASP as well for myelin-associated markers of brain (without hypothalamus) from CDK4 total KO mice. Our results showed that CDK4 deletion on hypothalamic astrocytes i) tends to decrease the proliferation ii) to increase the expression of some markers of the SASP as well iii) tends to increase the senescence-associated (SA) β- galactosidase staining. These results show that deletion of CDK4 seems to induce senescence of hypothalamic astrocytes. However, in contrast to the hypothalamus, the other brain areas of CDK4 KO mice do not present a difference in expression of genes coding of SASP although expression of myelin- associated genes decreased. Altogether these results suggest that CDK4 could be a key regulator of senescence of astrocytes, specifically in the hypothalamus. Further studies need to be performed to confirm these first observations and to understand the role of CDK4 in astrocytes from another brain area.