Mitochondrial and metabolic features of salugenesis and the healing cycle | Robert K. Naviaux (2023)


Pathogenesis and salugenesis are the first and second stages of the two-stage problem of disease production and health recovery. Salugenesis is the automatic, evolutionarily conserved, ontogenetic sequence of molecular, cellular, organ system, and behavioral changes that is used by living systems to heal. It is a whole-body process that begins with mitochondria and the cell. The stages of salugenesis define a circle that is energy- and resource-consuming, genetically programmed, and environmentally responsive. Energy and metabolic resources are provided by mitochondrial and metabolic transformations that drive the cell danger response (CDR) and create the three phases of the healing cycle: Phase 1 — Inflammation, Phase 2 — Proliferation, and Phase 3 — Differentiation. Each phase requires a different mitochondrial phenotype. Without different mitochondria there can be no healing. The rise and fall of extracellular ATP (eATP) signaling is a key driver of the mitochondrial and metabolic reprogramming required to progress through the healing cycle. Sphingolipid and cholesterol-enriched membrane lipid rafts act as rheostats for tuning cellular sensitivity to purinergic signaling. Abnormal persistence of any phase of the CDR inhibits the healing cycle, creates dysfunctional cellular mosaics, causes the symptoms of chronic disease, and accelerates the process of aging. New research reframes the rising tide of chronic disease around the world as a systems problem caused by the combined action of pathogenic triggers and anthropogenic factors that interfere with the mitochondrial functions needed for healing. Once chronic pain, disability, or disease is established, salugenesis-based therapies will start where pathogenesis-based therapies end.

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From Environmental Toxicants to the Cell Danger Response of Chronic Diseases to the Healing Cycle | Prof Robert Naviaux

The pace of change in the human ecosystem has accelerated rapidly in the past 30 years. These changes not only affect human health, but the health of plants and animals that share the environment with us. Nine keystone vertebrate, invertebrate and plant species have experienced extinctions or population crashes since the 1980s, and opportunistic human infections are on the rise. These crashes and infections can be traced to changes in metabolism that underlie epigenetics, innate, and adaptive immunity. Epigenetic and immunologic ripple effects have led to new Acquired Immunodeficiency Syndromes (AIDS) in plants and animals, and Acquired Autoimmune Disorders (AAIDS) in humans and domesticated animals. Autism is one of nearly a dozen new, neuroimmune and metabolic spectrum disorders (NIMS) that have emerged as a consequence of these new combinations of environmental factors that have never before been encountered by the human genome. This talk will showcase examples of AIDS, AAIDS, and NIMS that teach us about the unintended, and often-invisible environmental changes caused by human technological progress, and how these changes can be measured and managed systematically.

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