Identifying Regulators of Cellular Aging that can Prevent Alzheimer's Disease

ABSTRACT Aging is the leading risk factor for Alzheimer’s Disease (AD) and many other chronic diseases, with more than 6.5 million cases of AD in the US. Regulating or slowing cellular aging, particularly in microglia and astrocytes that regulate neuroimmunity, would have a major impact on the treatment of AD, but the proteins that control cellular aging processes are poorly understood. Cellular aging has been characterized into 9 “hallmarks” or phenotypes that define aged cells. Most hallmarks are a result of cellular stress, such as DNA damage and oxidation, and are inter-related in both their causes and outcomes. The cellular aging process is linked to dramatically altered gene expression, which is largely controlled by transcription factors (TFs). Longevity studies between species also suggest that TF activity can define the rate of aging. We hypothesize that TFs can modulate cellular aging and that identifying the TFs that play a role in aging processes will enable an entirely new generation of therapeutic targets with the potential to treat, delay, and possibly even prevent AD. The discovery of TFs that can improve the lifespan of patients would have a profound impact on the prevention and treatment of AD and many other diseases.