A Multi-Counter Architecture of Replicative Aging (MCARA)
- 1Georgia Longevity Alliance
Abstract
Human fibroblasts arrest after a finite number of divisions — even when telomerase keeps telomeres long and low oxygen protects mitochondria. I argue that the centriole functions as a stress integrator: when operating as a centrosome organizer, it accumulates polyglutamylation (polyE) on its tubulin in response to replicative and oxidative stress, remodeling its signaling surface — the Centriolar Aging-Associated Signaling Module (CAASM). When operating as a cilium organizer, polyE accumulation ceases. This functional duality — centrosome (stress-responsive, polyE-accumulating) versus cilium (signaling, non-accumulating) — makes the centriole a conditional entropy carrier. The framework (MCARA — Multi-Counter Architecture of Replicative Aging) is a hypothesis, not a confirmed theory: its centriolar component, CEDAR (Centriolar Entropy-Driven Aging Registry), sits at GRADE level V. It makes one falsifiable prediction: eliminating centrioles from fibroblasts before OSKM reprogramming should raise iPSC colony efficiency at least twofold. The experiment has not been reported. The centriole is hardware with a unique property: it cannot be repaired in situ, but it can be eliminated and created de novo — exactly what happens in meiosis, where oocyte centrioles are eliminated and sperm centrioles are restructured into seeds (not templates) for de novo centrioles in the blastomeres of the new organism. This distinguishes the centriole from the epigenome: the epigenome is reprogrammable software; the centriole is replaceable but not repairable hardware. The hardware/software distinction explains why partial reprogramming yields incomplete rejuvenation. A critical alternative interpretation — that centriole removal may increase reprogramming efficiency by impairing differentiation competence or suppressing Wnt signaling via ciliogenesis defects, rather than resetting an aging clock — is addressed in the experimental design. Either outcome is progress.
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BibTeX
@misc{tqemaladze2026multicounter,
title = {{A Multi-Counter Architecture of Replicative Aging (MCARA)}},
author = {Jaba Tqemaladze},
howpublished = {Research Square},
year = {2026},
month = jul,
doi = {10.21203/rs.3.rs-10320101/v1},
url = {https://doi.org/10.21203/rs.3.rs-10320101/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A Multi-Counter Architecture of Replicative Aging (MCARA)
AU - Jaba Tqemaladze
PY - 2026
DA - 2026/07/14
PB - Research Square
DO - 10.21203/rs.3.rs-10320101/v1
UR - https://doi.org/10.21203/rs.3.rs-10320101/v1
AB - Human fibroblasts arrest after a finite number of divisions — even when telomerase keeps telomeres long and low oxygen protects mitochondria. I argue that the centriole functions as a stress integrator: when operating as a centrosome organizer, it accumulates polyglutamylation (polyE) on its tubulin in response to replicative and oxidative stress, remodeling its signaling surface — the Centriolar Aging-Associated Signaling Module (CAASM). When operating as a cilium organizer, polyE accumulation ceases. This functional duality — centrosome (stress-responsive, polyE-accumulating) versus cilium (signaling, non-accumulating) — makes the centriole a conditional entropy carrier. The framework (MCARA — Multi-Counter Architecture of Replicative Aging) is a hypothesis, not a confirmed theory: its centriolar component, CEDAR (Centriolar Entropy-Driven Aging Registry), sits at GRADE level V. It makes one falsifiable prediction: eliminating centrioles from fibroblasts before OSKM reprogramming should raise iPSC colony efficiency at least twofold. The experiment has not been reported. The centriole is hardware with a unique property: it cannot be repaired in situ, but it can be eliminated and created de novo — exactly what happens in meiosis, where oocyte centrioles are eliminated and sperm centrioles are restructured into seeds (not templates) for de novo centrioles in the blastomeres of the new organism. This distinguishes the centriole from the epigenome: the epigenome is reprogrammable software; the centriole is replaceable but not repairable hardware. The hardware/software distinction explains why partial reprogramming yields incomplete rejuvenation. A critical alternative interpretation — that centriole removal may increase reprogramming efficiency by impairing differentiation competence or suppressing Wnt signaling via ciliogenesis defects, rather than resetting an aging clock — is addressed in the experimental design. Either outcome is progress.
ER -