Centrioles as Intracellular Timers of the Cell Cycle and Cell Fate

Abstract

The centrosome, and specifically its core centriolar components, is classically known for its structural roles in cell division and ciliogenesis. However, emerging evidence suggests a far more integrative function: centrioles may act as autonomous intracellular timers that encode cellular history and influence future decisions. This review synthesizes data from 41 studies (2010–2024) to evaluate the hypothesis that centrioles function as biological “clocks” for the cell cycle and determinants of cell fate. We present empirical evidence showing that centriole age, number, and structural state serve as quantifiable metrics that cells utilize to count divisions, time cell cycle phases, and determine division symmetry. The molecular basis of this timing involves the accumulation of age-specific post-translational modifications on mother centrioles, dynamic changes in pericentriolar material composition, and physical linkage to the nuclear lamina. A comparative analysis across embryonic stem cells, neural progenitors, senescent fibroblasts, and cancer cells reveals context-specific manifestations of this timer function, from safeguarding pluripotency to driving genomic instability. While alternative viewpoints on causality and universality exist, an integrative “Centriolar Regulatory Clock” model positions these organelles as critical information-processing hubs that compute temporal and spatial data to guide cell cycle progression, division mode, and ultimate fate. This reframing of centrioles from structural elements to computational timers opens novel therapeutic avenues in regenerative medicine, oncology, and research into aging.