The centriole as a fourth counter of replicative aging: a systems analysis of ARGUS, an open autonomous platform for lineage-scale surveillance

Replicative aging in dividing cells is commonly described through three resettable counters: telomere length, mitochondrial state, and chromatin organisation. We argue for a fourth: the centriole, a conserved microtubule-based organelle that every animal cell either keeps or eliminates. Three lines of evidence motivate the proposal. First, centriole fate is highly stereotyped: in Caenorhabditis elegans about 88% of somatic cells eliminate their centrioles during embryogenesis, and elimination is coupled to cell fate (Kalbfuss & Gönczy, 2023a). Second, centriole age measurably biases division geometry and cell fate in human cells, including asymmetric inheritance in stem cells (Thomas & Meraldi, 2024; Izumi et al., 2026). Third, unlike telomeres, mitochondria, and chromatin, the centriole has no known disposal-and-reassembly pathway in somatic cells, yet nature performs an analogous reset between meiosis I and the first blastomeres, at the cost of haploidization (Pierron et al., 2023). We present a systems analysis of ARGUS, an open, autonomous, low-cost fluorescence platform for lineage-scale surveillance of centrioles in living specimens, and of its four operating subsystems (OS1–OS4). The subsystems form an epistemic ladder. OS1 asks whether division geometry, summarised as a pre-registered Pedigree Score, predicts centriole fate (correlation). OS2 asks whether pedigree predicts convergence of fate across different lineages (prediction). OS3 tests causality through laser ablation (necessity) and centriole transplantation (sufficiency), and asks whether centriole elimination followed by de novo synthesis can reset cellular entropy without haploidization. OS4 adds inverted-geometry high-numerical-aperture imaging and contact-free optoelectronic-tweezer manipulation. Each stage carries pre-registered, falsifiable criteria and explicit go/no-go gates. We analyse the epistemic structure of the system, its failure modes, and its generalisability, and discuss what a testable fourth counter implies for aging biology and for open, autonomous biological instrumentation.

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Publication Details

Journal
Longevity Horizon
Published
2026-11-11
DOI
https://doi.org/10.65649/bdm4f1i2
Primary Topic
Microtubule and mitosis dynamics
Type
article
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article

The centriole as a fourth counter of replicative aging: a systems analysis of ARGUS, an open autonomous platform for lineage-scale surveillance

Ming Yao
Longevity Horizon
Microtubule and mitosis dynamics
article

The centriole as a fourth counter of replicative aging: a systems analysis of ARGUS, an open autonomous platform for lineage-scale surveillance

Ming Yao
article en

Abstract

Replicative aging in dividing cells is commonly described through three resettable counters: telomere length, mitochondrial state, and chromatin organisation. We argue for a fourth: the centriole, a conserved microtubule-based organelle that every animal cell either keeps or eliminates. Three lines of evidence motivate the proposal. First, centriole fate is highly stereotyped: in Caenorhabditis elegans about 88% of somatic cells eliminate their centrioles during embryogenesis, and elimination is coupled to cell fate (Kalbfuss & Gönczy, 2023a). Second, centriole age measurably biases division geometry and cell fate in human cells, including asymmetric inheritance in stem cells (Thomas & Meraldi, 2024; Izumi et al., 2026). Third, unlike telomeres, mitochondria, and chromatin, the centriole has no known disposal-and-reassembly pathway in somatic cells, yet nature performs an analogous reset between meiosis I and the first blastomeres, at the cost of haploidization (Pierron et al., 2023). We present a systems analysis of ARGUS, an open, autonomous, low-cost fluorescence platform for lineage-scale surveillance of centrioles in living specimens, and of its four operating subsystems (OS1–OS4). The subsystems form an epistemic ladder. OS1 asks whether division geometry, summarised as a pre-registered Pedigree Score, predicts centriole fate (correlation). OS2 asks whether pedigree predicts convergence of fate across different lineages (prediction). OS3 tests causality through laser ablation (necessity) and centriole transplantation (sufficiency), and asks whether centriole elimination followed by de novo synthesis can reset cellular entropy without haploidization. OS4 adds inverted-geometry high-numerical-aperture imaging and contact-free optoelectronic-tweezer manipulation. Each stage carries pre-registered, falsifiable criteria and explicit go/no-go gates. We analyse the epistemic structure of the system, its failure modes, and its generalisability, and discuss what a testable fourth counter implies for aging biology and for open, autonomous biological instrumentation.

Longevity HorizonVol. 2(6)
Chinese Academy of Sciences (CN)
Microtubule and mitosis dynamics
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