Cell Replacement to Reverse Brain Aging: Challenges, Pitfalls, and Opportunities.

Current antiaging strategies focusing on druggable targets have met with relatively limited success to date. Replacement of cells, tissues, and organs could provide an alternative means for targeting age-induced damage and potentially eliminating some of it. However, before this is a viable option, numerous challenges need to be addressed. Most notably, whether the brain, which defines our self-identity, is amenable to replacement therapies is unclear. Here, we consider whether progressive cell replacement is a potential approach to reverse brain aging without grossly altering function. We focus mainly on the neocortex, seat of our highest cognitive functions, because of abundant knowledge on neocortical development, plasticity, and how the neocortex can functionally incorporate new neurons. We outline the primary challenges for brain cell replacement, and key areas that require further investigation.