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Stability of Signaling Pathways during Aging-A Boolean Network Approach.

ABSTRACT: Biological pathways are thought to be robust against a variety of internal and external perturbations. Fail-safe mechanisms allow for compensation of perturbations to maintain the characteristic function of a pathway. Pathways can undergo changes during aging, which may lead to changes in their stability. Less stable or less robust pathways may be consequential to or increase the susceptibility of the development of diseases. Among others, NF- ? B signaling is a crucial pathway in the process of aging. The NF- ? B system is involved in the immune response and dealing with various internal and external stresses. Boolean networks as models of biological pathways allow for simulation of signaling behavior. They can help to identify which proposed mechanisms are biologically representative and which ones function but do not mirror physical processes-for instance, changes of signaling pathways during the aging process. Boolean networks can be inferred from time-series of gene expression data. This allows us to get insights into the changes of behavior of pathways such as NF- ? B signaling in aged organisms in comparison to young ones.

SUBMITTER: Schwab JD

PROVIDER: S-EPMC5745451 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Stability of Signaling Pathways during Aging-A Boolean Network Approach.

Schwab Julian Daniel JD Siegle Lea L Kühlwein Silke Daniela SD Kühl Michael M Kestler Hans Armin HA

Biology 20171218 4

Biological pathways are thought to be robust against a variety of internal and external perturbations. Fail-safe mechanisms allow for compensation of perturbations to maintain the characteristic function of a pathway. Pathways can undergo changes during aging, which may lead to changes in their stability. Less stable or less robust pathways may be consequential to or increase the susceptibility of the development of diseases. Among others, NF- κ B signaling is a crucial pathway in the process of ...[more]

PMID: 29258225

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Project description:Growing evidence suggests that healthy aging affects the configuration of large-scale functional brain networks. This includes reducing network modularity and local efficiency. However, the stability of these effects over time and their potential role in learning remain poorly understood. The goal of the present study was to further clarify previously reported age effects on "resting-state" networks, to test their reliability over time, and to assess their relation to subsequent learning during training. Resting-state fMRI data from 23 young (YA) and 20 older adults (OA) were acquired in 2 sessions 2 weeks apart. Graph-theoretic analyses identified both consistencies in network structure and differences in module composition between YA and OA, suggesting topological changes and less stability of functional network configuration with aging. Brain-wide, OA showed lower modularity and local efficiency compared to YA, consistent with the idea of age-related functional dedifferentiation, and these effects were replicable over time. At the level of individual networks, OA consistently showed greater participation and lower local efficiency and within-network connectivity in the cingulo-opercular network, as well as lower intra-network connectivity in the default-mode network and greater participation of the somato-sensorimotor network, suggesting age-related differential effects at the level of specialized brain modules. Finally, brain-wide network properties showed associations, albeit limited, with learning rates, as assessed with 10 days of computerized working memory training administered after the resting-state sessions, suggesting that baseline network configuration may influence subsequent learning outcomes. Identification of neural mechanisms associated with learning-induced plasticity is important for further clarifying whether and how such changes predict the magnitude and maintenance of training gains, as well as the extent and limits of cognitive transfer in both younger and older adults.

Dataset Information

Stability of Signaling Pathways during Aging-A Boolean Network Approach.

Publications

Stability of Signaling Pathways during Aging-A Boolean Network Approach.

Similar Datasets

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