11/10/2022 0 Comments Tor network diagram![]() ![]() The progression of aging depends on both the increasing rate of damage to DNA, RNA, proteins, and cellular organelles, as well as the gradual decline of cellular defense mechanisms against stress. It also allows us to identify potential network biomarkers for diagnosis and prognosis of age-related pathologies.Ĭellular aging is a multi-factorial complex phenotype, characterized by the accumulation of damaged cellular components over the organism’s life-span. ![]() The constructed effective response network greatly enhances understanding of the mechanisms underlying the aging process and helps in identifying new targets for further investigation of anti-aging regimes. ![]() Rather, it predicts transcriptional changes and post-translational modifications in response to TOR inhibition. Our approach, unlike experimental methods, is not limited to specific aspects of cellular response. This network is hypothesized to mediate life-span extension in response to TOR inhibition. We use this framework to identify the most relevant transcription factors in mediating the observed transcriptional response, and to construct the effective response network of the TOR pathway. We propose a novel statistical framework for integrating information flow scores, the set of differentially expressed genes in response to rapamycin treatment, and the transcriptional regulatory network. These rankings must be normalized for degree bias, appropriately interpreted, and mapped to associated roles in pathways. Information flow scores provide an aggregate ranking of relevance of proteins with respect to the TOR signaling pathway. By constructing a high-level functional map of TOR downstream effectors, we show that our approach is not only capable of recapturing previously known pathways, but also suggests potential targets for future studies. We adopt a systematic approach for tracing information flow from the TOR complex and use it to identify relevant signaling elements. In this paper, we present the first comprehensive, computationally derived map of TOR downstream effectors, with the objective of discovering key lifespan mediators, their crosstalk, and high-level organization. Both genetic and pharmacological interventions that inhibit the TOR pathway exhibit a similar phenotype, which is not further amplified by CR. The target of rapamycin (TOR) has been shown to play a key role in mediating healthspan extension in response to CR by integrating different signals that monitor nutrient-availability and orchestrating various components of cellular machinery in response. Calorie restriction (CR) is one of the most conserved non-genetic interventions that extends healthspan in evolutionarily distant species, ranging from yeast to mammals. ![]()
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