Targeted Forgetting Rejuvenation: Engram-Specific Partial Reprogramming via Rac1-Dependent Complement Tagging

Title: Targeted Forgetting Rejuvenation: Engram-Specific Partial Reprogramming via Rac1-Dependent Complement Tagging Abstract: Partial reprogramming via transient expression of Oct4, Sox2, Klf4 (OSK) reverses epigenetic aging but application in the central nervous system is limited by risks of teratoma formation and erasure of identity-encoding engrams. This study proposes Targeted Forgetting Rejuvenation (TFR): We hypothesize that physiological active forgetting, mediated by Rac1 GTPase signaling and microglial complement-dependent synaptic pruning, defines a permissive window for safe rejuvenation. Synthesis of quantitative data indicates a labile engram fraction of ~22.3% marked by high Rac1-GTP activity and C1q deposition. Selective delivery of OSK to this C1q-positive labile fraction is predicted to reset epigenetic age by ~12% per cycle while preserving stable memory circuits, providing a solution to the identity preservation problem in brain rejuvenation. Author: Zakaria Zarwal Affiliation: Independent Researcher, Essaouira, Morocco License: CC BY 4.0