PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and Heterogeneity

ABSTRACT Purpose Premature cellular senescence is a pivotal process in aging and age‐related diseases, triggered by various stressors. However, this is not a homogeneous phenotype, but a heterogeneous cellular state composed of multiple senescence programs with different compositions. Therefore, und...

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Main Authors: Vinícius Pierdoná, Patrícia Lavandoski, Rafael Moura Maurmann, Guilherme Antônio Borges, Jose Carlos Merino Mombach, Fátima Theresinha Costa Rodrigues Guma, Florencia María Barbé‐Tuana
Format: Article
Language:English
Published: Wiley 2025-04-01
Series:Aging Medicine
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Online Access:https://doi.org/10.1002/agm2.70020
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author Vinícius Pierdoná
Patrícia Lavandoski
Rafael Moura Maurmann
Guilherme Antônio Borges
Jose Carlos Merino Mombach
Fátima Theresinha Costa Rodrigues Guma
Florencia María Barbé‐Tuana
author_facet Vinícius Pierdoná
Patrícia Lavandoski
Rafael Moura Maurmann
Guilherme Antônio Borges
Jose Carlos Merino Mombach
Fátima Theresinha Costa Rodrigues Guma
Florencia María Barbé‐Tuana
author_sort Vinícius Pierdoná
collection DOAJ
description ABSTRACT Purpose Premature cellular senescence is a pivotal process in aging and age‐related diseases, triggered by various stressors. However, this is not a homogeneous phenotype, but a heterogeneous cellular state composed of multiple senescence programs with different compositions. Therefore, understanding the complex dynamics of senescence programs requires a systemic approach. We introduce PseudoCell, a multivalued logical regulatory network designed to explore the molecular intricacies of premature senescence. Methods PseudoCell integrates key senescence signaling pathways and molecular mechanisms, offering a versatile platform for investigating diverse premature senescence programs initiated by different stimuli. Results Validation through simulation of classical senescence programs, including oxidative stress‐induced senescence and oncogene‐induced senescence, demonstrates its ability to replicate molecular signatures consistent with empirical data. Additionally, we explore the role of CCL11, a novel senescence‐associated molecule, through simulations that reveal potential pathways and mechanisms underlying CCL11‐mediated senescence induction. Conclusions In conclusion, PseudoCell provides a systematic approach to dissecting premature senescence programs and uncovering novel regulatory mechanisms.
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publishDate 2025-04-01
publisher Wiley
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series Aging Medicine
spelling doaj-art-b6122b3000bc4b1bbd3b36aa3d55b1072025-08-20T02:22:06ZengWileyAging Medicine2475-03602025-04-018214515510.1002/agm2.70020PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and HeterogeneityVinícius Pierdoná0Patrícia Lavandoski1Rafael Moura Maurmann2Guilherme Antônio Borges3Jose Carlos Merino Mombach4Fátima Theresinha Costa Rodrigues Guma5Florencia María Barbé‐Tuana6Programa de Pós‐Graduação Em Ciências Biológicas: Bioquímica Do Departamento de Bioquímica Universidade Federal Do Rio Grande Do Sul Porto Alegre Rio Grande do Sul BrazilPrograma de Pós‐Graduação Em Ciências Biológicas: Bioquímica Do Departamento de Bioquímica Universidade Federal Do Rio Grande Do Sul Porto Alegre Rio Grande do Sul BrazilPrograma de Pós‐Graduação Em Biologia Celular e Molecular da Escola de Ciências da Saúde e da Vida ‐ Pontifícia Universidade Católica Do Rio Grande Do Sul Porto Alegre Rio Grande do Sul BrazilDepartamento de Engenharia Electrotécnica e de Computadores Universidade de Coimbra Coimbra PortugalDepartamento de Física Universidade Federal de Santa Maria Santa Maria Rio Grande do Sul BrazilPrograma de Pós‐Graduação Em Ciências Biológicas: Bioquímica Do Departamento de Bioquímica Universidade Federal Do Rio Grande Do Sul Porto Alegre Rio Grande do Sul BrazilPrograma de Pós‐Graduação Em Biologia Celular e Molecular da Escola de Ciências da Saúde e da Vida ‐ Pontifícia Universidade Católica Do Rio Grande Do Sul Porto Alegre Rio Grande do Sul BrazilABSTRACT Purpose Premature cellular senescence is a pivotal process in aging and age‐related diseases, triggered by various stressors. However, this is not a homogeneous phenotype, but a heterogeneous cellular state composed of multiple senescence programs with different compositions. Therefore, understanding the complex dynamics of senescence programs requires a systemic approach. We introduce PseudoCell, a multivalued logical regulatory network designed to explore the molecular intricacies of premature senescence. Methods PseudoCell integrates key senescence signaling pathways and molecular mechanisms, offering a versatile platform for investigating diverse premature senescence programs initiated by different stimuli. Results Validation through simulation of classical senescence programs, including oxidative stress‐induced senescence and oncogene‐induced senescence, demonstrates its ability to replicate molecular signatures consistent with empirical data. Additionally, we explore the role of CCL11, a novel senescence‐associated molecule, through simulations that reveal potential pathways and mechanisms underlying CCL11‐mediated senescence induction. Conclusions In conclusion, PseudoCell provides a systematic approach to dissecting premature senescence programs and uncovering novel regulatory mechanisms.https://doi.org/10.1002/agm2.70020agingbioinformaticscellular senescencein silico modelingpremature senescence
spellingShingle Vinícius Pierdoná
Patrícia Lavandoski
Rafael Moura Maurmann
Guilherme Antônio Borges
Jose Carlos Merino Mombach
Fátima Theresinha Costa Rodrigues Guma
Florencia María Barbé‐Tuana
PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and Heterogeneity
Aging Medicine
aging
bioinformatics
cellular senescence
in silico modeling
premature senescence
title PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and Heterogeneity
title_full PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and Heterogeneity
title_fullStr PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and Heterogeneity
title_full_unstemmed PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and Heterogeneity
title_short PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and Heterogeneity
title_sort pseudocell a multivalued logical regulatory network to investigate premature senescence dynamics and heterogeneity
topic aging
bioinformatics
cellular senescence
in silico modeling
premature senescence
url https://doi.org/10.1002/agm2.70020
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