Rule-Based Cell Systems Model of Aging using Feedback Loop Motifs Mediated by Stress Responses

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-κB 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

Gran Ballet del Marqués de Cuevas

De cada obra s'ha digitalitzat un programa sencer. De la resta s'han digitalitzat les parts que són diferents.Empresa: José F. ArquerOrquestra Simfònica del Gran Teatre del Liceu, directors André Girard i Gustave CloezPrograma de la temporada de ballet de la primavera del 1956 amb el següent repertori: Tragedia en Verona, de George Skibine amb música de Piotr Ilix Txaikovski; Esmeralda, de Cesare Pugni; Doña Inés de Castro, d'Ana Ricarda amb música de Joaquín Serra; Don Quijote de Ludwig Minkus; La Princesa Aurora, de Txaikovsk