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COMPLEX TIME: Adaptation, Aging, & Arrow of Time

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Contact: Caitlin Lorraine McShea, Program Manager, cmcshea@santafe.edu

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"%3AAbstract%2FAlthough-20accumulation-20of-20molecular-20damage-20is-20suggested-20to-20be-20an-20important-20molecular-20mechanism-20of-20aging%2C-20a-20quantitative-20link-20between-20the-20dynamics-20of-20damage-20accumulation-20and-20mortality-20of-20species-20has-20so-20far-20remained-20elusive.-20To-20address-20this-20question%2C-20we-20examine-20stability-20properties-20of-20a-20generic-20gene-20regulatory-20network-20%28GRN%29-20and-20demonstrate-20that-20many-20characteristics-20of-20aging-20and-20the-20associated-20population-20mortality-20rate-20emerge-20as-20inherent-20properties-20of-20the-20critical-20dynamics-20of-20gene-20regulation-20and-20metabolic-20levels.-20Based-20on-20the-20analysis-20of-20age-2Ddependent-20changes-20in-20gene-2Dexpression-20and-20metabolic-20profiles-20in-20Drosophila-20melanogaster%2C-20we-20explicitly-20show-20that-20the-20underlying-20GRNs-20are-20nearly-20critical-20and-20inherently-20unstable.-20This-20instability-20manifests-20itself-20as-20aging-20in-20the-20form-20of-20distortion-20of-20gene-20expression-20and-20metabolic-20profiles-20with-20age%2C-20and-20causes-20the-20characteristic-20increase-20in-20mortality-20rate-20with-20age-20as-20described-20by-20a-20form-20of-20the-20Gompertz-20law.-20In-20addition%2C-20we-20explain-20late-2Dlife-20mortality-20deceleration-20observed-20at-20very-20late-20ages-20for-20large-20populations.-20We-20show-20that-20aging-20contains-20a-20stochastic-20component%2C-20related-20to-20accumulation-20of-20regulatory-20errors-20in-20transcription-2Ftranslation-2Fmetabolic-20pathways-20due-20to-20imperfection-20of-20signaling-20cascades-20in-20the-20network-20and-20of-20responses-20to-20environmental-20factors.-20We-20also-20establish-20that-20there-20is-20a-20strong-20deterministic-20component%2C-20suggesting-20genetic-20control.-20Since-20mortality-20in-20humans%2C-20where-20it-20is-20characterized-20best%2C-20is-20strongly-20associated-20with-20the-20incidence-20of-20age-2Drelated-20diseases%2C-20our-20findings-20support-20the-20idea-20that-20aging-20is-20the-20driving-20force-20behind-20the-20development-20of-20chronic-20human-20diseases." contains a listed "%" character as part of the property label and has therefore been classified as invalid.

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