伪细胞：一种用于研究早衰动力学和异质性的多值逻辑调控网络。
PseudoCell: A Multivalued Logical Regulatory Network to Investigate Premature Senescence Dynamics and Heterogeneity.
作者信息
Pierdoná Vinícius, Lavandoski Patrícia, Maurmann Rafael Moura, Borges Guilherme Antônio, Mombach Jose Carlos Merino, Guma Fátima Theresinha Costa Rodrigues, Barbé-Tuana Florencia María
机构信息
Programa de Pós-Graduação Em Ciências Biológicas: Bioquímica Do Departamento de Bioquímica Universidade Federal Do Rio Grande Do Sul Porto Alegre Rio Grande do Sul Brazil.
Programa 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 Brazil.
出版信息
Aging Med (Milton). 2025 Apr 18;8(2):145-155. doi: 10.1002/agm2.70020. eCollection 2025 Apr.
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.
目的
细胞过早衰老由多种应激源触发，是衰老及与年龄相关疾病中的关键过程。然而，这并非一种均一的表型，而是由具有不同组成的多个衰老程序构成的异质性细胞状态。因此，理解衰老程序的复杂动态需要一种系统方法。我们引入了PseudoCell，这是一个多值逻辑调控网络，旨在探索过早衰老的分子复杂性。
方法
PseudoCell整合了关键衰老信号通路和分子机制，为研究由不同刺激引发的多种过早衰老程序提供了一个通用平台。
结果
通过对经典衰老程序（包括氧化应激诱导的衰老和癌基因诱导的衰老）进行模拟验证，证明了其复制与实验数据一致的分子特征的能力。此外，我们通过模拟探索了一种新型衰老相关分子CCL11的作用，这些模拟揭示了CCL11介导衰老诱导的潜在途径和机制。
结论
总之，PseudoCell为剖析过早衰老程序和揭示新的调控机制提供了一种系统方法。
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