The relationship between organismal aging and debilitating chronic diseases, including Alzheimer’s disease, is clearly linked. One potential culprit driving age-associated pathologies are senescent cells (SnCs), which are characterized by a permanent cell cycle arrest. These cells accumulate with advancing age and at sites of dysfunction in a number of age-related diseases. This association led to the hypothesis that SnCs actively drive tissue deterioration and are not simply innocent bystanders in these conditions. A proposed mechanism behind this dynamic process is the acquisition of a senescence-associated secretory phenotype, or SASP, where SnCs produce and secrete a variety of growth factors, matrix metalloproteinases, chemokines and pro-inflammatory cytokines. Many recent studies, including those from my laboratory, have demonstrated that SnCs shorten life and actively drive age-related pathology, including neurodegeneration, in mice. In addition to neurofibrillary tangles and amyloid beta plaques, Alzheimer’s disease patients exhibit increased indicators of cellular senescence. Recently, we have demonstrated that treating mice to prevent accumulation of SnCs led to attenuation of tau-dependent degeneration and cognitive loss. As pharmacological modulation of SnCs appears to be on the horizon, it is imperative to determine whether removal of SnCs from established AD patients has beneficial impacts. We first will test this using mouse model systems with degeneration. Additionally, we will explore whether SnCs are a common occurrence in AD mouse models.