BioAcyl Corp
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Naviaux, R. K. (2019). Metabolic features and regulation of the healing cycle—A new model for chronic disease pathogenesis and treatment. Mitochondrion, 46, 278–297. Added by: Dr. Enrique Feoli (16/10/2020, 20:02) Last edited by: Dr. Enrique Feoli (13/11/2020, 12:45) |
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| Resource type: Journal Article DOI: 10.1016/J.MITO.2018.08.001 ID no. (ISBN etc.): 1567-7249 BibTeX citation key: Naviaux2019 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Healing cycle Creators: Naviaux Collection: Mitochondrion |
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| Abstract |
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Without healing, multicellular life on Earth would not exist. Without healing, one injury predisposes to another, leading to disability, chronic disease, accelerated aging, and death. Over 60% of adults and 30% of children and teens in the United States now live with a chronic illness. Advances in mass spectrometry and metabolomics have given scientists a new lens for studying health and disease. This study defines the healing cycle in metabolic terms and reframes the pathophysiology of chronic illness as the result of metabolic signaling abnormalities that block healing and cause the normal stages of the cell danger response (CDR) to persist abnormally. Once an injury occurs, active progress through the stages of healing is driven by sequential changes in cellular bioenergetics and the disposition of oxygen and carbon skeletons used for fuel, signaling, defense, repair, and recovery. >100 chronic illnesses can be organized into three persistent stages of the CDR. One hundred and two targetable chemosensory G-protein coupled and ionotropic receptors are presented that regulate the CDR and healing. Metabokines are signaling molecules derived from metabolism that regulate these receptors. Reframing the pathogenesis of chronic illness in this way, as a systems problem that maintains disease, rather than focusing on remote trigger(s) that caused the initial injury, permits new research to focus on novel signaling therapies to unblock the healing cycle, and restore health when other approaches have failed.
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| Notes |
Fig. 1. A metabolic model of the health and healing cycles. Health is a dynamic process that requires regular cycling of wakeful activity and restorative sleep. The healing or damage cycle is activated when the cellular stress exceeds the capacity of restorative sleep to repair damage and restore normal cell-cell communication. CDR1 is devoted to damage control, innate immunity, inflammation, and clean up. CDR2 supports cell proliferation for biomass replacement, and blastema formation in tissues with augmented regeneration capacity. CDR3 begins when cell proliferation and migration have stopped, and recently mitotic cells can begin to differentiate and take on organ-specific functions. Abbreviations: eATP; extracelllular ATP; CP1–3: checkpoints 1–3; DAMPs: damage-associated molecular patterns; DARMs: damage-associated reactive metabolites. |