The Mitochondria, Brain Fog, and Aging

 

 

I’d like to present the mitochondrial perspective on energy and Brain fog. So I’ve recently asked you three questions. Have you been able to keep up with all the latest news? Do you find yourself forgetting what you've just saw, heard or read ? How often have you tried to recall something that was "just on the tip of your tongue" but that just suddenly  vanished? We talked about brain fog with the inability to concentrate or focus, having poor memory or difficulty with recall, and a loss of mental clarity. I mentioned the various causes that I've helped correct in the people I've worked with. We focused on food allergies or intolerances, a 14 day reset and detoxification program, and gave you a brief introduction on mitochondria in a cartoon last week.

So the causes of all disease is Inflammation which lead to oxidative stress, immunity dysfunction, mitochondrial damage, cell death, and then organ death.

What are the origins of these power plants that are present in almost every cell in our body? Plants have solar power plants called chloroplasts but we partnered with an ? Ancient power producing bacteria. Mitochondria make energy for us and plants as well. These are some facts about the Mitochondrial genetics. They have their own nuclear region and DNA. Their DNA are not protected as much as our DNA and any injury such as radiation, metabolic waste products like reactive oxygen species, and environmental toxins damage mitochondrial DNA first.  Our mitochondria are inherited from our mothers (via the egg, not the sperm).  Maternal health and exposure to toxins determines the baseline mitochondria we have. Genetic tracing can used to trace ancestry from the maternal branches of families.

 

So what are the benefits of mitochondria?

They allow us to use oxygen to generate 32 ATP energy units per molecule of glucose through the Krebs cycle.  Without mitochondria we make only 2 ATP energy units in a process called glycolysis. They regulate cell aging and a process called autophagy or the cell death pathways which is missing cancer cells. They regulate calcium levels in the cell. They participate in heat generation (thermogenesis) in brown fat. They contribute to immunity and inflammation. They play a keypart in cell survival.

 

The Major consumers of energy: brain, heart, immune, muscles

Mitochondria are like metabolic engines. Combustion engines in our cars produce waste products and “excess heat/stress." Mitochondria produce reactive Oxygen Species (ROS) or free radicals that need to be neutralized.  Superoxide (02-) is a reactive oxygen species (ROS), which is the name given to highly reactive molecules that contain oxygen, is the main source of ROS in cells. Left alone, it can cause damage like a combustions engine can have viscosity breakdown or overheat.  Fortunately superoxide can be converted to hydrogen peroxide H2O2  another ROS but is a step away from being converted by enzymes to water or H20 which is obviously safe.  If the hydrogen peroxide is not converted , a very reactive hydroxyl molecule *OH can form and can’t be eliminated by enzymes

Antioxidants protect and defend against ROS attack

The Mitochondrial ROS scavenging system is a powerful antioxidant defense system that searches for  ROS as they are generated.  Molecules that hunt and eliminate ROS are called ROS scavengers. Superoxide dismutase (SOD)  is an enzyme responsible for the conversion of superoxide into hydrogen peroxide. There is a cytosolic form of SOD, SOD1 or Cu/Zn-SOD (because it binds copper and zinc), but mitochondria have their own form, SOD2 or Mn-SOD (because it binds manganese).  Hydrogen peroxide (H2O2) can then be eliminated by enzymes that convert it into water (H2O).  The danger is without enzymatic conversion, hydrogen peroxide can degrade into the hydroxyl radical (*OH) which his extremely damaging

Mitochondrial ROS Scavenging System: Glutathione

Glutathione peroxidase (GPx) is found in mitochondria and in the cytosol (the cell). It eliminates H2O2 with the assistance of the redox molecule glutathione (GSH).  Glutathione is made from 3 peptides: glutamate, cysteine, and glycine.  Cysteine is responsible for its biological activity and is the rate-limiting factor in glutathione synthesis. Cells can make more GSH if adequate amounts of these three amino acids are in the diet. Because cysteine is rate-limiting, increasing cysteine, the dietary supplement N-acetylcysteine (NAC), may boost GSH production.

Mitochondrial ROS Scavenging System: Peroxiredoxins and Catalase

Peroxiredoxins (Prx), also found in mitochondria and in the cytosol, act in a similar way to glutathione perioxidase (GPx).  They reduce hydrogen peroxide (H2O2) with the help of the redox molecule thioredoxin.  Catalase is very effective at detoxifying large amounts of hydrogen perioxide (H2O2).  It can rapidly decomposes H2O2 into water and oxygen. Catalase is found in a type of cellular organelles called peroxisomes

Mitochondrial Fitness: Keeping mitochondria healthy

Mitochondrial fitness is essential for our health in general. Loss of mitochondrial function is a hallmark of aging and many age-related disorders.  Maintenance of mitochondrial fitness is linked to increased healthspan and longevity. Mitochondrial disease can have multiple causes from environmental toxins, genetics, and chronic infections to name a few. Since Mitochondria are present in almost all cells of the body symptoms can be mild or severe and can be wide ranging as listed below. The Brain, heart, lungs, eyes and muscles are primarily affected.

This disease causes problems with thinking, walking, talking, eating, breathing,-just about anything.

Mitochondrial dysfunction is a cause of many familar diseases: Autism, Alzheimer's, Parkinson's ALS, Huntington's , muscular dystrophy, epilepsy, chronic fatigue, diabetes, fibromyalgia, and cancer

Brain-setzures. stroke-like episodes. depression, cognitive impairments, language delay, autism, learning disabilities, movement disorders, fatigue

Eyes-cataracts, droopy eye lids

Heart and lungs - cardio weakness, shortness of breath, heart failure

Stomach/ Intestines: constipation, diarrhea, digestive difficulty

Endocrine diabetes, hormone deficiencies, thyroid problems

Muscles (legs and arms) muscle weakness, pain

Nerves-pain, hearing loss, diziness, fainting, excerise intolerance

 

Michondrial Networks

There are hundreds to thousands of mitochondria in a single cell.

The Network of mitochondria working together is essential for cellular well being and adaptations to behaviors linked to healthy aging like restricting calories or exercise.

The mitochondrial network within each cell is constantly adapting itself to our lifestyle and environement.

As we get older the number and network of mitochondria decline and we don’t have enough energy for our cells and tissues to do the things we want to do

Mitochondiral Quality Control (MQC)

The reshaping  of mitochondrial networks is MQC

MQC and its processes work to maintain mitochondrial fitness at the  molecular, mitochondrial , and cellular levels

MQC monitors any damage  or environmental changes and allows the mitochondrial networks to reshape themselves to adapt to diet, lifestyle, and the environment

PROTEIN QUALITY CONTROL KEEPS MITOCHONDRIA HEALTHY

Another set of molecular mitochondrial quality control (MQC )processes aims at repairing and restoring the function of damaged proteins, or at replacing irreversibly damaged proteins

The protein quality control (PQC) system is made up of a set of mitochondrial chaperones and proteases, and of cytosolic proteolytic systems that reside  and are associated with the outer mitochondrial membrane

Chaperones are proteins that assist the folding of other proteins (this is needed to move proteins through cell and mitochondrial membranes).

Proteases are enzymes that break down proteins.

Chaperones like the heat shock proteins HSP22, HSP60 and HSP70 aide the  mitochondrial PQC by sorting and folding misfolded or unfolded proteins back to their native structures, and by breaking up  proteins that are stuck together inappropriately.

They are part of a damage repair system and are a critical component of countering a long recognized aging process called “Loss of Proteostasis” (or loss of protein homeostasis).

When the accumulation of damaged or unfolded proteins overpowers the mitochondrial refolding and repairing capacity, it triggers  a  mitochondrial unfolded protein response which is a stress response that increases the expression of chaperones and proteases.

Oxidative damage of proteins can be irreversible, meaning the proteins cannot be repaired.

Irreversibly damaged proteins have an adverse affect on cellular function

Part of the  “Aging as Damage Accumulation” theory of aging

Fortunately, cells can elimate Irreversibly damaged proteins through proteolysis which is the breakdown of proteins

This is achieved through the proteolytic PQC system, where mitochondrial proteases and cytosolic proteolytic systems like the ubiquitin–proteasome system (UPS) degrade damaged or aggregated proteins.

These are then replaced by new proteins produced by de novo biosynthetic pathways.

PQC also occurs at the mitochondrial DNA level by a set of mitochondrial DNA repair pathways that find and correct mtDNA mutations.

MITOCHONDRIAL NETWORKS RESHAPE THEMSELVES

Mitochondrial fission is the opposite of fusion. Fission generates two smaller mitochondria.

Fission is essential for mitochondrial duplication and biogenesis which is the creation of new mitochondria.  It’s also required for cell division.

Also, much like fusion, fission plays a role in damage control, because it allows for the separation of damage. Mitochondrial content can be mixed and separated, allowing the isolation of damaged molecules or structures.

Smaller mitochondria with different properties can be generated, separating the damaged from the functional

A damaged mitochondrion may recover and fuse with another mitochondrion, but if the damage is irreparable, it will be degraded (i.e., the mitochondrion will be eliminated)

MITOCHONDRIA GET RID OF IRREVERSIBLE DAMAGE

Autophagy which means ‘self-eating’ occurs when a cell degrades and recycles its own contents, particularly damaged proteins and organelles, for cellular recycling  and homeostasis maintenance.

Aging as a process of damage accumulation is one of the main theories of aging. By cleaning up cellular debris and preventing it from accumulating, autophagy helps keep cells performing at a younger level.

Mitophagy (mitochondrial autophagy) is a specific type of autophagy that selectively degrades damaged mitochondria. It is a tightly regulated MQC process that acts at the organellar level

Non-selective autophagy and selective mitophagy are of great biological relevance because they allow the elimination of irreversibly damaged and dysfunctional mitochondria that have been segregated by mitochondrial fission

HOW MITOCHONDRIAL NETWORKS GET FITTER

Mitochondrial biogenesis is the generation of new mitochondrial content. It is the opposite of mitophagy.

New mitochondria are produced from pre-existing ones through fusion and fission events, by adding new mitochondrial proteins, and extending the mitochondrial membranes.

So Mitochondrial biogenesis is,  in essence an increase in mitochondrial mass

Mitophagy and mitochondrial biogenesis share signaling pathways and work in a coordinated way to remove damaged mitochondrial material and add new functional mitochondrial mass and act to maintain optimal mitochondrial functionality

MQC IS ESSENTIAL FOR HEALTHY AGING

Mitochondria have developed  a  set of  of interconnected processes, collectively called the mitochondrial quality control (MQC)

Its role is to minimize damage,  repair whenever possible, but get rid of damage if it becomes irreparable.

Our cells age when the MCQ can’t keep up with the amount of damage that’s being done.

At the same time, there is also a natural age-related decrease in the efficacy of antioxidant defenses and other MQC processes,

Cellular senescence accelerates and ultimately affects the the of tissues and organs. From there  high‐energy‐demanding tissues such as muscles, brain, heart, and immune system are compromised.

 

So to optimize  the mitochondrial quality control we need minimize environmental toxin exposures, nourish our mitochondria with appropriate micronutrients, bioactive phytonutrients, and essential molecules such as L carnitine, alpha lipoic acid, and N-acylecysteine.

Acetyl L-Carnitine functions by facilitating long-chain fatty acid entry into mitochondria, allowing for oxidation and subsequent energy production.

Alpha-lipoic acid is a naturally occurring short chain fatty acid, serving as an important cofactor for many enzyme complexes including the mitochondrial respiratory enzymes. Is is also an antioxidant.

 N-acetylcysteine (NAC), is a precursor of glutathione, is a widely used thiol-containing antioxidant and modulates the intracellular redox state. It eliminates H2O2 with the assistance of Glutathione peroxidase (GPx).

Once mitochondria are optimized with products such as Mito Max, detoxification such as the 14 day reset or detoxification program are even more effective and also repairing the GI tract and having the energy to rebalance the immune system can also take place more efficiently. Brain function and mental fatigue are restored if there are no other causative factors.

 

Next week, we will discuss the brain and mild cognitive decline in more detail. I hope to see you then.

So if you'd like to take advantage of the time you have sheltered at home to do the GI Reset Program please call our office to schedule a telephone or telemedicine video chat consultation.

For more information on food intolerances, mitochondria,  exercise to benefit repiratory and immune functions, sleep, supplements, foods, and stress reduction to help boost the immune system please see the blogs on https://www.allfunctionalhealth.com/blog

Author
Jeffrey Mark, M.D. Helping clients with compassionate and comprehensive medical care for over 25 years with 4 board certifications in functional medicine, gastroenterology, internal medicine, and anti-aging/ regenerative medicine . IFMCP, ABIM Gastroenterology, NPAS Internal Medicine, ABAARM.

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