Eliminate, Reprogram, Rebuild: A Proposal for a Centriole Reset Consortium

Partial reprogramming via OSK transcription factors resets the epigenome but does not address the physical age accumulated in the centriole. The mother centriole ages through three modes — chemical (polyglutamylation), geometric (over-elongation), and structural (cartwheel deformation) — and templates its own duplication, propagating all three to daughter cells. No transcription factor can touch it. We hypothesize that eliminating the old centriole before reprogramming, then rebuilding it de novo after totipotency is achieved, will enable complete cellular rejuvenation — reaching a state that OSK alone cannot. The protocol proceeds in three steps: (1) purify the cell by removing the aged centriole, restoring telomeres, and selecting healthy mitochondria; (2) achieve transient totipotency via DUX4, EZH2 inhibition, and DPPA3; (3) rebuild young centrioles de novo and differentiate to safe adult stem cells. The protocol is specified with quantitative readouts, control groups, and risk mitigations. No step has been experimentally validated; the document serves as a framework for collaborative testing. An alternative — OSK-mediated partial reprogramming without centriole manipulation — already extends healthspan in vivo, providing a gentler, validated path for comparison.