Artikel ; Online: The choice of the objective function in flux balance analysis is crucial for predicting replicative lifespans in yeast.
2022 Band 17, Heft 10, Seite(n) e0276112
Abstract: Flux balance analysis (FBA) is a powerful tool to study genome-scale models of the cellular metabolism, based on finding the optimal flux distributions over the network. While the objective function is crucial for the outcome, its choice, even though ... ...
Abstract | Flux balance analysis (FBA) is a powerful tool to study genome-scale models of the cellular metabolism, based on finding the optimal flux distributions over the network. While the objective function is crucial for the outcome, its choice, even though motivated by evolutionary arguments, has not been directly connected to related measures. Here, we used an available multi-scale mathematical model of yeast replicative ageing, integrating cellular metabolism, nutrient sensing and damage accumulation, to systematically test the effect of commonly used objective functions on features of replicative ageing in budding yeast, such as the number of cell divisions and the corresponding time between divisions. The simulations confirmed that assuming maximal growth is essential for reaching realistic lifespans. The usage of the parsimonious solution or the additional maximisation of a growth-independent energy cost can improve lifespan predictions, explained by either increased respiratory activity using resources otherwise allocated to cellular growth or by enhancing antioxidative activity, specifically in early life. Our work provides a new perspective on choosing the objective function in FBA by connecting it to replicative ageing. |
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Mesh-Begriff(e) | Cell Cycle ; DNA Replication ; Longevity ; Models, Biological ; Saccharomyces cerevisiae/metabolism |
Sprache | Englisch |
Erscheinungsdatum | 2022-10-13 |
Erscheinungsland | United States |
Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 2267670-3 |
ISSN | 1932-6203 ; 1932-6203 |
ISSN (online) | 1932-6203 |
ISSN | 1932-6203 |
DOI | 10.1371/journal.pone.0276112 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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