Salugenesis and the Story of Mitochondria

Published July 2024

Since World War II, modern medicine has made great strides by dealing so effectively with the triggers and risks associated with acute infections that people, at least in the developed world, are less likely to die from physical injuries, viral or bacterial infections, poisoning, or vitamin deficiencies. This pathogenesis approach, despite its success, is a siloed, engineering-style approach with a focus on dealing with symptoms, and not necessarily the root causes of diseases.

In the last fifty to hundred years, the use of chemicals (7,000 plus used alone in agriculture, industry, and personal care) and plastics (more than 80 billion pounds of plastics generated each year) has been accelerating and these chemicals have been polluting our air, water, soil, and food. The combination of toxic chemicals and lifestyle changes in our diet, exercise, sleep cycles, and stress levels are damaging our mitochondria.1

The World Health Organization estimates that over 70% of deaths around the world occur as a result of noncommunicable diseases, such as heart disease, kidney disease, diabetes, dementia and cancer, caused by chronic inflammation.2 (Check out a previous article on this blog for a detailed read on chronic inflammation.)

The U.S. Centers of Disease Control and Prevention define chronic disease as any condition that is not cured within 12 months. Typically, interventions for chronic conditions, for example insulin for diabetes or statins for heart disease, often have to be taken for life because they are a response to the disease profile and not necessarily as a response to the root cause.

From pathogenesis to salugenesis

Until recently, there was no term to describe the reverse of pathogenesis – how healing and recovery happens. Robert K. Naviaux, MD, PhD, founder of Naviaux Lab and the Mitochondrial and Metabolic Disease Center at the University of California San Diego School of Medicine, coined the word salugenesis from Salus, the Roman goddess of health, safety, well-being, and prosperity.³

Dr. Naviaux defines salugenesis as a systems approach which is a “evolutionarily conserved, and highly choreographed sequence of molecular steps that comprise the healing cycle.” This approach includes interventions that promote completion of the healing cycle and are not limited to drugs, but can also be exercise, stress relief, adaptogens, and more.

He posits that if the last 5,000 years of human medicine can be called the first book of medicine focused on pathogenesis, we now need to turn towards salugenesis as the subject of the second book of medicine. Instead of using engineering logic or a reductionist and siloed approach to understanding disease, where the focus is on finding the pathogens or triggers that cause disease and mechanisms for removing them, we need to take the salugenesis approach, which calls for the use of biological logic where every molecule, cell and organ is interconnected. This systems approach will help us understand the body’s innate healing process.

Note that salugenesis is not to be confused with salutogenesis; this latter term was first referred to by medical sociologist Aaron Antonovsky in his 1979 book, Health, Stress and Coping. He defines salutogenesis as an approach focused on lifestyle skills and coping skills to promote well-being; whereas, salugenesis focuses on the metabolic, cellular, and organ of the healing cycle. Dr. Naviaux considers salutogenesis and salugenesis to be complementary to each other.

Cell Danger Response, the body’s innate ability to heal

The human body normally operates in a state of homeostasis, where it automatically and continuously adapts to its environment and keeps its internal systems in balance for optimal functioning. The three key areas regulated by the body are temperature, blood pressure, and blood sugar.

Increasingly, we live in a world where the levels of environmental insults (the cause of a physical or mental injury) are not normal, and rapidly scaling:

Chemical insults, such as heavy metals mercury, nickel, lead; the chemical Bisphenol A (BPA) commonly used in water bottles, food cans; agricultural pesticides (more than a billion pounds of pesticides are used annually in the US alone to combat weeds and pests)
Biological insults, such as viruses, bacteria, parasites
Physical insults, such as excessive heat or cold, excess salt or sugar, radiation
Psychological insults, such as verbal abuse, bullying, harassment, humiliation, social media, war

The insults listed above are not normal in that human beings have not had to deal with them until much recently and they require more than the normal regulation of homeostasis that our bodies have evolved to provide.

When we experience an internal or external insult, the cells protect themselves via a standard response that Dr. Naviaux has called the Cell Danger Response (CDR). He defines CDR as an evolutionarily conserved metabolic response that protects the cells and the host from harm.

The CDR — a key part of the body’s natural immune system response — has three stages and once triggered, requires the cells to successfully go through each CDR stage before healing can happen. Once this process is completed, the cells are returned to the state of homeostasis where they are once again ready to handle the next insult.

The mitochondria play the starring role in sensing and responding to physical, chemical, and microbial insults inside and outside the cells.

As soon as they sense danger, the mitochondria trigger CDR. Dr. Naviaux has compared the criticality of the mitochondria’s role in triggering CDR to that of canaries in coal mines where in the 19th century, they used to signal the presence of the deadly, clear and odorless carbon monoxide gas.⁴

Mitochondria, fundamental regulators of Cell Danger Response

Each mitochondrion includes approximately 1500 proteins (also known as the mitochondrial proteome) and these proteins are regulated by chemical, physical, or microbial changes to the cell. In his research paper on the metabolic function of salugenesis, Dr. Naviaux explains that these changes in the mitochondrial proteins are used to “signal safety or danger in the cell, alter gene expression, trigger the healing response, and adjust fitness and susceptibility to chronic illness. These changes even help to adjust the rate of aging in response to environmental stress.”³

While mitochondria are the primary energy factories of the human body, producing more than 90% of the energy needed by the body to function, when the cell experiences a threat, the mitochondria become defensive in nature to protect the cell from further injury.

This defensive mechanism results in the mitochondria down regulating and the CDR shows up in a number of functional changes,⁴ including:

Shifting of cellular metabolism from polymer synthesis to monomer synthesis so that the pathogens cannot hijack the cell resources
Stiffening of the cell membranes to stop further infection
Release of antiviral and antimicrobial chemicals by the cell
Increasing mitochondrial biogenesis, mitophagy, and autophagy to remove the pathogens
Alteration of the gene expression by DNA methylation
Mobilization of retroviruses
Warning neighboring cells of the danger

What happens when the Cell Danger Response cannot resolve

When we are faced with the new level of insults in our environment today, the Cell Danger Response (CDR) cannot resolve or complete, and instead persists, the inflammation becomes chronic and leads to a wide range of chronic diseases and conditions, such as, food allergies, asthma, entropy, PTSD, diabetes, heart disease, type 2 diabetes, rheumatoid arthritis, autoimmune disorders, accelerated aging among others.⁵

Chronic inflammation damages and depletes mitochondria and as a result, they are unable to generate enough of the energy required for the cells and the body to heal. Also, to be noted, even when the insult is removed, the damage may be so great that the body goes into a downward spiral.

How to increase and support healthy mitochondria

Given the key role played by mitochondria in protecting us from threats and insults from the environment, it is important to consider how to increase the number of mitochondria, and how to support healthy and abundant mitochondria for the production of more energy for healing and reversing the downward spiral of cellular decline, inflammation, low energy, disease, and accelerated aging.

Indeed, healthy and abundant mitochondria are key to an improved quality of life from the inside out.

Common suggestions for increasing mitochondria or supporting healthy mitochondria include a diet rich in antioxidants, good sleep, exposure to optimal sunlight, meditation, relaxation and other stress reducing techniques, dietary supplements, and exercise (aerobic, strength training, or brisk walks).

References

Naviaux, Robert K. (2020, March). Perspective: Cell danger response Biology—The new science that connects environmental health with mitochondria and the rising tide of chronic illness. Mitochondrion, Vol51. https://www.sciencedirect.com/science/article/pii/S1567724919302922?via%3Dihub
World Health Organization. Noncommunicable Diseases. https://www.who.int/health-topics/noncommunicable-diseases#tab=tab_1
Naviaux, Robert K. (2022, Dec. 7). Mitochondrial and metabolic features of salugenesis and the healing cycle. The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine. https://www.sciencedirect.com/science/article/pii/S1567724923000351
Naviaux, Robert K. (2020, May). The Cell Danger Response: a new paradigm for understanding chronic disease? IHCAN Mitochondrial Medicine. https://aonm.org/wp-content/uploads/2021/07/Cell-Danger-Response-IHCAN.pdf
Naviaux, Robert K. (2014, May) Metabolic features of the cell danger response. Mitochondrion, e18(2014). https://www.sciencedirect.com/science/article/pii/S1567724913002390?via%3Dihub