The Centriolar Imperative

The repeated observation that transplantation of young stem cells extends both healthspan and lifespan across diverse organisms—from Drosophila to mice and humans—presents a persistent mechanistic puzzle. Prevailing theories of aging, focused on telomere attrition, epigenetic drift, or macromolecular damage, fail to provide a unified, cell-autonomous explanation for why young cells, specifically, confer such profound systemic benefits. This review synthesizes convergent evidence through the lens of the Centriolar Damage Accumulation Theory of Aging (CDATA). CDATA posits that the non-dividing mother centriole, a microtubule-organizing center and basal body, accumulates irreversible post-translational modifications (PTMs)—notably excessive polyglutamylation—across the lifespan of a stem cell. This damage impairs its core functions: mitotic fidelity, ciliogenesis, and consequent Hedgehog/Wnt signal transduction, leading to flawed niche sensing and a decline in self-renewal capacity. We argue that young stem cells possess mother centrioles with less PTM damage, thereby restoring precise division geometry and ciliary signaling upon transplantation. Critically, CDATA generates a unique, falsifiable Relapse Prediction (P11): functional rescue by young cells is inherently temporary, with relapse kinetics dictated by the recipient cell’s division count, not calendar time, due to the irreversible nature of PTM accumulation. This contrasts with theories predicting stable rescue. We review supportive evidence from Drosophila centrosome misorientation, murine muscle and hematopoietic stem cell (HSC) studies, and human clinical outcomes. We further discuss therapeutic strategies targeting centriolar deglutamylases (e.g., CCP1/AGBL5) and the implications for biobanking. CDATA offers a unified framework explaining the conserved efficacy of young stem cell transplantation and provides a roadmap for novel, mechanism-based anti-aging interventions.