ArticlePLoS computational biology2010
Rule-based cell systems model of aging using feedback loop motifs mediated by stress responses.
Article in PLoS computational biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 54 citations in OpenAlex.
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- Divergent Aging of Isogenic Yeast Cells Revealed through Single-Cell Phenotypic Dynamics.Cell systems · 2019Article
- Representing dynamic biological networks with multi-scale probabilistic models.Communications biology · 2019Article
- Simulation of Cellular Energy Restriction in Quiescence (ERiQ)-A Theoretical Model for Aging.Biology · 2017Article
- Understanding the mTOR signaling pathway via mathematical modeling.Wiley interdisciplinary reviews. Systems biology and medicine · 2017Review
- Modelling the molecular mechanisms of aging.Bioscience reports · 2017Review
- Understanding the physiology of the ageing individual: computational modelling of changes in metabolism and endurance.Interface focus · 2016Review
- Complex systems dynamics in aging: new evidence, continuing questions.Biogerontology · 2016Review
- Mathematical modelling of metabolic regulation in aging.Metabolites · 2015Review
- Introductory review of computational cell cycle modeling.Methods in molecular biology (Clifton, N.J.) · 2014Review
- Paradoxical and bidirectional drug effects.Drug safety · 2012Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Investigating the complex systems dynamics of the aging process requires integration of a broad range of cellular processes describing damage and functional decline co-existing with adaptive and protective regulatory mechanisms. We evolve an integrated generic cell network to represent the connectivity of key cellular mechanisms structured into positive and negative feedback loop motifs centrally important for aging. The conceptual network is casted into a fuzzy-logic, hybrid-intelligent framework based on interaction rules assembled from a priori knowledge. Based upon a classical homeostatic representation of cellular energy metabolism, we first demonstrate how positive-feedback loops accelerate damage and decline consistent with a vicious cycle. This model is iteratively extended towards an adaptive response model by incorporating protective negative-feedback loop circuits. Time-lapse simulations of the adaptive response model uncover how transcriptional and translational changes, mediated by stress sensors NF-kappaB and mTOR, counteract accumulating damage and dysfunction by modulating mitochondrial respiration, metabolic fluxes, biosynthesis, and autophagy, crucial for cellular survival. The model allows consideration of lifespan optimization scenarios with respect to fitness criteria using a sensitivity analysis. Our work establishes a novel extendable and scalable computational approach capable to connect tractable molecular mechanisms with cellular network dynamics underlying the emerging aging phenotype.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.