Genomic Instability-Induced Senescence in Brain Aging and Alzheimer's Disease

! Narrative The largest risk factor for developing a host of pathologies, most prominently Alzheimer’s disease (AD) and other age-related dementias, is age. How aging-associated cellular impairments affect neurodegeneration is not clear. Here we propose that age related accumulation of large-scale genomic instability in non-neuronal cells promotes senescence. Genomic instability-induced senescent astrocytes could fail to accomplish their neuronal nursing functions and/or acquire neurotoxic properties and be particularly detrimental for AD progression. Our results will help elucidate basic mechanisms of neurodegeneration at old age. !