Expansion of the neocortex and protection from neurodegeneration by in vivo transient reprogramming.

Yi-Ru Shen, Sofia Zaballa, Xavier Bech, Anna Sancho-Balsells, Irene Rodríguez-Navarro, Carmen Cifuentes-Díaz, Gönül Seyit-Bremer, Seung Hee Chun, Tobias Straub, Jordi Abante, Iñaki Merino-Valverde, Laia Richart, Vipul Gupta, Hao-Yi Li, Ivan Ballasch, Noelia Alcázar, Jordi Alberch, Josep M Canals, Maria Abad, Manuel Serrano, Rüdiger Klein, Albert Giralt, Daniel Del Toro

Department of Molecules-Signaling-Development, Max-Planck Institute for Biological Intelligence, 82152 Martinsried, Germany.Department of Molecules-Signaling-Development, Max-Planck Institute for Biological Intelligence, 82152 Martinsried, Germany. · pubmed

Paper

Abstract

Yamanaka factors (YFs) can reverse some aging features in mammalian tissues, but their effects on the brain remain largely unexplored. Here, we induced YFs in the mouse brain in a controlled spatiotemporal manner in two different scenarios: brain development and adult stages in the context of neurodegeneration. Embryonic induction of YFs perturbed cell identity of both progenitors and neurons, but transient and low-level expression is tolerated by these cells. Under these conditions, YF induction led to progenitor expansion, an increased number of upper cortical neurons and glia, and enhanced motor and social behavior in adult mice. Additionally, controlled YF induction is tolerated by principal neurons in the adult dorsal hippocampus and prevented the development of several hallmarks of Alzheimer's disease, including cognitive decline and altered molecular signatures, in the 5xFAD mouse model. These results highlight the powerful impact of YFs on neural proliferation and their potential use in brain disorders.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper explores the use of Yamanaka factors to induce neural proliferation and potentially mitigate neurodegeneration, which aligns with the broader goals of longevity research by addressing mechanisms that could underlie age-related cognitive decline. However, while the findings are interesting and contribute to our understanding of brain health in the context of aging, they primarily focus on a specific application rather than directly targeting the root causes of aging itself. Thus, the impact is solid but limited in the broader context of longevity research.

Author of this paper? Send a correction.