CDATA Computational Validation and Mechanics
DOI:
https://doi.org/10.65649/c86yh745Keywords:
Aging, Centriole, CDATA, Digital Twin, Stem Cells, Asymmetric Division, Primary Cilium, Computational Biology, Hallmarks of Aging, Tissue HomeostasisAbstract
The Centriolar Damage Accumulation Theory of Aging (CDATA) proposes that the mother centriole in adult stem cells functions as an irreversible molecular damage accumulator, whose progressive deterioration drives the decline of tissue homeostasis and organismal aging. While theoretically compelling, CDATA has faced valid criticisms regarding the correlation-vs.-causation problem, the non-universality of asymmetric centriole inheritance, the specificity of the centriole over other long-lived organelles, and an internal contradiction regarding cancer biology. Here I present the Cell DT platform — a computational digital twin of CDATA — that provides the first mechanistic, quantitative, and internally consistent model of centriolar aging. Implemented in Rust using an Entity-Component-System (ECS) architecture, the platform models five molecular damage types (protein carbonylation, tubulin hyperacetylation, protein aggregation, phosphorylation dysregulation, and distal appendage loss), two downstream failure tracks (Track A: ciliary signaling failure; Track B: asymmetric division failure), and a positive ROS feedback loop. Simulations of 36,500 daily time steps reproduce a human lifespan of approximately 78–83 years under normal conditions, approximately 15–20 years under progeria-like parameters (5× damage rates), and approximately 130 years under longevity-associated parameters (0.6× rates). I systematically address each major critique of CDATA, showing that: (1) the digital twin provides mechanistic causal evidence beyond correlation; (2) stochastic asymmetric division suffices to drive CDATA dynamics even in tissues with predominantly symmetric divisions; (3) the centriole is uniquely positioned as a non-renewable, template-replicated hub integrating both ciliary and spindle functions; and (4) the cancer-aging paradox is resolved by two distinct failure modes of the same underlying mechanism. I conclude that CDATA is a falsifiable, computationally validated hypothesis that warrants experimental testing with the priority experiments outlined herein.
References
Bobinnec Y, Khodjakov A, Mir LM, et al. (1998). Centriole disassembly in vivo and its effect on centrosome structure and function in vertebrate cells. J Cell Biol. 143(6):1575-1589.
Bornens M. (2012). The centrosome in cells and organisms. Science. 335(6067):422-426.
Brodland GW. (2015). How computational models can help unlock biological systems. Semin Cell Dev Biol. 47-48:62-73.
Campisi J. (2013). Aging, cellular senescence, and cancer. Annu Rev Physiol. 75:685-705.
Cheung HH, Liu X, Canterel-Thouennon L, et al. (2014). Telomerase protects Werner syndrome lineage-specific stem cells from premature aging. Stem Cell Reports. 2(4):534-546.
Conduit PT, Raff JW. (2010). Cnn dynamics drive centrosome size asymmetry to ensure daughter centriole retention in Drosophila neuroblasts. Curr Biol. 20(24):2187-2192.
Cristofalo VJ, Allen RG, Pignolo RJ, Martin BG, Beck JC. (1998). Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation. Proc Natl Acad Sci USA. 95(18):10614-10619.
Cuervo AM, Dice JF. (2000). Age-related decline in chaperone-mediated autophagy. J Biol Chem. 275(40):31505-31513.
D'Angelo MA, Raices M, Bhattacharya S, et al. (2009). Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells. Cell. 136(2):284-295.
Epstein JM. (2008). Why model? J Artif Soc Soc Simul. 11(4):12.
Furukawa S, Fujita T, Shimabukuro M, et al. (2004). Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 114(12):1752-1761.
Gonczy P. (2015). Centrosomes and cancer: revisiting a long-standing relationship. Nat Rev Cancer. 15(11):639-652.
Gordon LB, Rothman FG, Lopez-Otin C, Misteli T. (2014). Progeria: a paradigm for translational medicine. Cell. 156(3):400-407.
Habib SJ, Chen BC, Tsai FC, et al. (2013). A localized Wnt signal orients asymmetric stem cell division in vitro. Science. 339(6126):1445-1448.
Hayflick L. (1965). The limited in vitro lifetime of human diploid cell strains. Exp Cell Res. 37:614-636.
Jaba, T. (2022). Dasatinib and quercetin: short-term simultaneous administration yields senolytic effect in humans. Issues and Developments in Medicine and Medical Research Vol. 2, 22-31.
Jove M, Naudi A, Aledo JC, et al. (2014). Plasma long-chain free fatty acids predict mammalian longevity. Sci Rep. 3:3346.
Khodjakov A, Cole RW, McEwen BF, Buttle KF, Rieder CL. (1997). Chromosome fragments possessing only one kinetochore can congress to the spindle equator. J Cell Biol. 136(2):229-240.
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. (2013). The hallmarks of aging. Cell. 153(6):1194-1217.
Moore MN, Murphy SM. (2009). Mitochondrial reactive oxygen species and the antioxidant defense system. Clin Biochem. 42(9):859-869.
Nigg EA, Holland AJ. (2018). Once and only once: mechanisms of centriole duplication and their deregulation in disease. Nat Rev Mol Cell Biol. 19(5):297-312.
Pearl J. (2009). Causality: Models, Reasoning, and Inference. 2nd ed. Cambridge University Press.
Prosser SL, Pelletier L. (2020). Centriolar satellite biogenesis and function in vertebrate cells. J Cell Sci. 133(1):jcs197533.
Ritsma L, Ellenbroek SI, Zomer A, et al. (2014). Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature. 507(7492):362-365.
Robine JM, Allard M. (1998). The oldest human. Science. 279(5358):1834-1835.
Savas JN, Toyama BH, Xu T, Yates JR 3rd, Bhaskara M. (2012). Extremely long-lived nuclear pore proteins in the rat brain. Science. 335(6071):942.
Scaffidi P, Misteli T. (2008). Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing. Nat Cell Biol. 10(4):452-459.
Tkemaladze JV, Chichinadze KN. (2005). Centriolar mechanisms of differentiation and replicative aging of higher animal cells. Biochemistry (Moscow). 70(11):1288-1303.
Tkemaladze J. (2022). Reduction, proliferation, and differentiation defects of stem cells over time: a consequence of selective accumulation of old centrioles in the stem cells? Mol Biol Rep. https://doi.org/10.1007/s11033-022-08203-5.
Tkemaladze J. (2025a). Old Centrioles Make Old Bodies. Annals of Rejuvenation Science. 1(1). doi: 10.65649/yx9sn772.
Tkemaladze J. (2025b). The Centriolar Theory of Differentiation Explains the Biological Meaning of the Centriolar Theory of Organismal Aging. Longevity Horizon. 1(3). doi: 10.5281/zenodo.15057288.
Wang X, Tsai JW, Imai JH, et al. (2009). Asymmetric centrosome inheritance maintains neural progenitor cell cycle kinetics. Nature. 461(7266):947-955.
Yamashita YM, Mahowald AP, Perlin JR, Fuller MT. (2007). Asymmetric inheritance of mother versus daughter centrosome in stem cell division. Science. 315(5811):518-521.
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