31. Summary
Interruptions in the molecular stages of the healing cycle may be at the root of many complex, chronic illnesses. Three stages of the cell danger response (CDR1, 2, and 3) comprise the healing cycle. These stages are triggered by stress or injury and controlled by changes in mitochondrial function and metabolism (
Fig. 1,
Fig. 2,
Table 2). Many metabolites are metabokines that bind to dedicated receptors and signal when a cell is ready to enter the next stage of healing (
Fig. 4,
Fig. 5). Purinergic signaling from the release and metabolism of extracellular nucleotides plays an important role in all stages of the healing cycle (
Fig. 1). Programmed changes in the differentiation state of mitochondria, known as M0, M1, and M2-polarized organelles, and corresponding changes in cellular redox and the repurposing of cellular energy for cell defense and healing, also play fundamental roles (
Fig. 2,
Table 3) (
Naviaux, 2017). When a stage of the healing cycle cannot be completed, dysfunctional cells accumulate that contain developmentally inappropriate forms of mitochondria, organ function is compromised, and chronic illness results (
Fig. 3). Over 100 chronic illnesses can be classified according to the stage of the CDR that is blocked (
Table 1). Unblocking therapies directed at stimulating the completion of the healing cycle by regulating metabokine signaling hold promise as a new approach to treatment. A small clinical trial of the antipurinergic drug suramin in autism spectrum disorder (ASD) has shown promise for this approach (
Naviaux, 2017;
Naviaux et al., 2017). Metabolic addiction to the chemistry produced by different stages of the CDR can occur. When this happens, it can create a life-long risk of relapse or slow return to chronic illness if diet and lifestyle interventions are not maintained.
Prevention and treatment of chronic illness require distinctly different, but complementary approaches. New cases of chronic illness can be
prevented by reducing the environmental risks that trigger the damage cycle of the CDR, and by promoting nutritional and life-style changes that promote resilience and maintain the health cycle (
Fig. 1). However, once illness has occurred in a given patient, the opportunity for prevention is lost, and a perfect storm of multiple triggers can usually be identified. Many triggers are remote and no longer present. Once any remaining triggers have been identified and removed, and any symptoms or primed sensitivities caused by the metabolic memory of those triggers have been treated, a new approach to
treatment is required to improve the chances of completing the healing cycle and achieving a full recovery. By shifting the focus away from the
initial causes, to the metabolic factors and signaling pathways that
maintain chronic illness by blocking progress through the healing cycle, new research will be stimulated and novel treatments will follow.
