Centriolar Damage Accumulation Drives Replicative Senescence

The Hayflick limit — the finite replicative capacity of somatic cells — is conventionally attributed to telomere shortening or oxidative stress. However, stem cells in their native hypoxic niches (1–3% O₂) maintain telomerase activity and exhibit low intracellular ROS, yet they still undergo replicative senescence and reach a finite Hayflick limit (approximately 200 population doublings for human bronchial basal progenitors). This paradox renders telomere-centric and oxidative stress theories insufficient as complete explanations. We present the Centriolar Damage Accumulation Theory of Aging (CDATA), a quantitative framework proposing that non-repairable damage to the mother centriole constitutes a third, independent, and uniquely possible factor that drives replicative senescence even when telomeres are maintained and oxidative stress is minimized. CDATA introduces a damage variable D that accumulates over cell divisions, a mitochondrial shield parameter (mito_shield) modulating centriolar ROS exposure, and a critical damage threshold D_crit. A Rust-based computational simulator (Cell-DT v3.4) reproduces experimentally measured Hayflick limits. The model predicts that even under physiological hypoxia (1–3% O₂) with maximum telomerase activity and minimal ROS, centriolar damage accumulation continues and ultimately triggers senescence after a finite number of divisions. Five testable experimental predictions are presented. CDATA offers a unifying mechanistic account of replicative aging that explains why stem cells in their native niches — despite telomerase and low ROS — still exhaust their replicative capacity.