Strategic Timekeepers
DOI:
https://doi.org/10.65649/62kmtm81Keywords:
Centriole, Cellular Aging, Post-Translational Modifications, Stem Cell Fate, Asymmetric Division, Mitotic Spindle, Organismal SenescenceAbstract
For over a century, centrioles have been defined by their role as architects of the mitotic spindle. This review synthesizes contemporary evidence to propose a paradigm shift: centrioles are strategic timekeepers of the cell. They function not as simple clocks but as custodians of cellular time, encoding a history of divisions and stresses through accumulating post-translational modifications and proteomic changes. This molecular archive, stored on one of the cell's most stable structures, is subsequently interpreted by the cell via mechanical, signaling, and proteostatic pathways to dictate fundamental fate decisions—proliferation, differentiation, senescence, or apoptosis. This centriolar timekeeping function operates across a hierarchy, interacting with circadian oscillators, telomeric and epigenetic clocks, and crucially influencing organismal aging through its role in stem cell fate and asymmetric division. We develop an integrative "Centriolar Timeline" model, describing how the accrual of neutral (maturity) and pathological (damage) marks directs cellular trajectories. This model positions the centriole as a unique bio-physical interface that transforms linear chronological time into non-linear biological fate. Re-conceptualizing centrioles as central processors of temporal information has profound implications for understanding development, aging, and diseases like cancer, and suggests novel therapeutic avenues in regenerative medicine and gerontology aimed at modulating this deep-time cellular memory. The Centrosomal Ledger hypothesis is inherently untestable without omics-based approaches, as it posits that cellular memory is encoded not in single molecular markers but in distributed, multivariate structural states of the centrosome. Only system-level omics analyses can capture the weak yet coordinated molecular patterns, temporal integration, and state-dependent signatures required to render this model experimentally falsifiable
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