Fragile X Syndrome (FXS), a frequent form of inherited intellectual disability and a leading monogenic cause of autism, is caused by lack/reduction of fragile X mental retardation protein (FMRP), an RNA-binding protein involved in several aspects of RNA metabolism. Abnormal expression of proteins at synapses underlies brain dysfunction in FXS. FMRP is also implicated in DNA damage response and is a component of stress granules (SGs), cytoplasmatic aggregates that form in response to stress and are protective against apoptosis. Evidence in the mouse model of FXS suggests an excess of oxidizing agents in the brain; however, how neurons and glial cells cope with oxidative stress in the absence of FMRP is unknown. Oxidative stress and DNA damage can also trigger cellular senescence. Therefore, we investigated both sensitivity to stress and senescence in FXS mice.We examined SGs formation and cell survival in wild-type (WT) and Fmr1 knockout (KO) cultured neurons and astrocytes after exposure to oxidative stress by immunocytochemistry and MTT assay. We used senescence-associated-b-galactosidase (SA-b-gal) assay to reveal the senescent phenotype in WT and Fmr1 KO brain slices.We detected: 1. a lower number of SGs in Fmr1 KO astrocytes and 2. a lower cell survival in Fmr1 KO neurons and astrocytes compared to WT astrocytes upon exposure to oxidative stress; 3. an increased SA-b-gal staining in Fmr1 KO brains compared to WT counterparts. These results suggest that lack of FMRP sensitizes to oxidative stress-induced damage and accelerates senescence, possibly contributing to brain dysfunction in FXS.