MCARA: The Centriole as a Fourth Counter in Cellular Aging: A Hypothesis

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Cells divide a finite number of times, and the limit is not fully explained by telomeres or mitochondrial damage. This paper proposes that the centriole, the microtubule cylinder at the core of the centrosome, records how many division cycles a cell has survived. The centriole and the primary cilium are two states of a single organelle: in the ciliary state it is short, anchored at the membrane, and receives developmental signals; in the centrosome state the cilium is resorbed and the cell divides. Across successive cycles the balance can shift toward the centrosome state, and the cumulative ratio is inscribed in the organelle as polyglutamylation (polyE), a tubulin modification that accumulates during the centrosome phase but not during the ciliary phase. Four lines of evidence support the proposal. In C. elegans, 551 of 558 cells eliminate their centrioles upon differentiation. In Drosophila oocytes, forced retention of the old centrosome breaks totipotency. In planarians, stem cells lack centrioles, which appear only when a cell commits to a fate. In mammals, the older mother centriole segregates asymmetrically and shapes daughter cell fate, and a centriolar microprotein, miP-FERMT3, triggers p53-independent senescence and increases with age. A single experiment can test the hypothesis: remove centrioles from a fibroblast, add Yamanaka factors, and count colonies. If the centriole anchors differentiation, its removal should lift the lock. The centriole would then be one of four counters, centriole, telomere, mitochondrion, and epigenome, that run in parallel, so that protecting three of them leaves the fourth counting.