Salugenesis (The Healing Cycle) is Certainly Worth Research Funding

Understanding Pathogenesis is only half of the story. In Regenerative Philosophy, focus on the processes of renewal and regeneration with the same urgency should lead to improved health.

Trillions of dollars have been spent on understanding the causes and processes of disease, with careful avoidance of causal analysis that could implicate medical exposures. In contrast, the basic science of understanding healing processes has been woefully underfunded.

Dr. Robert Naviaux of the The Mitochondrial and Metabolic Disease Center, Departments of Medicine, Pediatrics, and Pathology, University of California, San Diego School of Medicine has just published an overview of the study of healing processes: Salugenesis.

Pathogenesis and salugenesis are terms used to describe how diseases form and how the body recovers health. Salugenesis is like the body's inbuilt repair system. It's a series of steps that living things go through to heal themselves, starting at the smallest level with our cells and their power sources, the mitochondria.

The process of healing is a cycle that goes through three phases: inflammation, cell multiplication, and differentiation (where cells become specialized for specific tasks). Each phase needs a different type of mitochondria, which provides the energy for the healing process. The changes in the type of mitochondria are driven by signaling molecules called extracellular ATP (eATP).

Cell membrane components called sphingolipids and cholesterol-enriched lipid rafts help regulate how sensitive cells are to these signals. If any phase of this healing cycle persists for too long, it can interfere with the overall healing process, leading to chronic diseases and speeding up the aging process.

Recent research suggests that the increasing rates of chronic disease worldwide can be seen as a result of both disease-causing triggers and human-made factors that disrupt the mitochondrial functions needed for healing. Once chronic pain or disease sets in, therapies based on the concept of salugenesis could pick up where conventional, disease-focused treatments leave off. These therapies aim to support and enhance the body's natural healing process.

From his overview, the primary foci of the science of salugenesis include:

1. Is tissue defense, repair, and remodeling possible if mitochondrial fusion-fission dynamics, or mitochondrial protein, or DNA synthesis are arrested?

2. Can the cell-system phenotypes of inflammation (M1), multipotential proliferation (M0), or differentiation and memory (M2) be accomplished without changes in the mitochondria-cell system phenotypes that shift the corresponding bioenergetic programs from glycolysis, through aerobic glycolysis, to oxidative phosphorylation?

3. Can new experimental models be developed that reproducibly capture the programmatic changes in the dynamical states—the process—of mitochondrial and cellular transitions that are needed to heal after injury or illness?

4. Can a new class of therapeutics be developed that target the governing dynamics of the healing cycle, facilitate the transitions between phases, and increase the number of cells that successfully complete the cycle after injury?

5. Can tissue dysfunction associated with chronic illness or aging be improved by interventions that 1) recover arrested cells and stimulate them to complete their path through the healing cycle, or 2) delete senescent cells with senolytics?

6. Are the mental health and physical benefits of exercise dependent on eATP release, and its conversion to eADP, eAMP, and eAdenosine, for normal purinergic signaling?

7. What is the role of eATP signaling-associated inflammation in complex neurodevelopmental and neurodegenerative disorders like autism spectrum disorder (ASD), amyotrophic lateral sclerosis (ALS), and Alzheimer’s dementia?

8. What is the role of eATP signaling-associated inflammation in complex mental health phenotypes like chronic pain, post-traumatic stress disorder (PTSD), gun and domestic violence, anxiety, and depression with suicidal ideation?

9. Can new anti-purinergic drugs and pannexin 1 channel inhibitors reduce the most disabling symptoms of ASD, ALS, chronic pain, PTSD, Long-COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and post-Lyme syndrome?

10. Can the rising tide of chronic illness observed in the past 50 years be slowed or turned back by international efforts to curb the release of pollutants from household, agricultural, medical, veterinary, and industrial sources?

11. Can biological aging be slowed and the health span increased if incomplete healing and the resulting dysfunctional cellular mosaics are reduced by decreasing the number of cells lost or arrested after each turn of the healing cycle?

These are regenerative ideas indeed. The full article is open access.

Naviaux, R. 2023. Mitochondrial and metabolic features of salugenesis and the healing cycle. Mitochondrion 70:131-163.