The Centriole as a Candidate Division Counter in Stem-Cell Aging

Abstract

Background. Replicative aging of stem cells requires a mechanism counting cell divisions. Centrioles — organelles with mother–daughter asymmetry and no de novo generation in most somatic cells — are candidate division counters: their geometry may accumulate mitotic-age information. Hypothesis. The centriole acts as a division counter in stem-cell aging: structural parameters (length, cartwheel integrity, daughter-relative positioning) change predictably with each division and contribute to senescence entry. Proposed validation. We present a falsifiable, pre-registered protocol: (i) expansion microscopy of human hematopoietic stem cells at defined division numbers; (ii) correlative live-imaging of mother centriole morphology across passages; (iii) perturbation of centriole assembly (PLK4/CEP350) with readout of replicative capacity; (iv) statistical model linking centriolar parameters to division count. Significance. Confirming the centriole as a division counter would identify a tractable target for interventions in stem-cell aging.