The build-up of deleterious proteins is one of the biggest problems in aging. The brain, the organ most sensitive to this phenomenon, seeks to maintain the correct balance by the process known as proteostasis but this process declines with aging. Reduced proteostasis causes major age-related diseases such as Alzheimer’s Disease, Parkinson’s Disease, and prion diseases, where aberrant proteins are known to associate with such diseases. Being able to restore proteostasis is likely to slow age-related decline in brain function, but the challenges are to find chemo preventatives that can enhance proteostasis to youthful levels, and to know how to administer these chemopreventative agents. A combination of epidemiology and studies in a convenient model system are providing approaches to find answers to these important questions.