Nerves and Aging

  How to Protect the Nervous System - Nerves to Live to 100?


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Nerves - and the Centenarian Diet

Wikipedia, "A nerve is an enclosed, cable-like bundle of axons (nerve fibers, the long and slender projections of neurons) in the peripheral nervous system (PNS). A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons to peripheral organs and appendages. Neurons are sometimes called nerve cells, though this term is potentially misleading since many neurons do not form nerves, and nerves also include non-neuronal Schwann cells that coat the axons in myelin.

The Nervous System | Diet Ramifications

The Nervous System (Wiki) is your body's decision and communication center. The Central Nervous System (CNS) is made up of the brain and the spinal cord whereas the Peripheral Nervous System (PNS) is made up of nerves (neurons). Together they control every part of your daily life, from breathing and blinking to helping you memorize facts for a test. Or in modern terms - thumb control.

(A) Different neuropathies are associated with ER stress contributing to axonal degeneration. (B) Targeting ER stress may promote axonal regeneration. Strategies to alleviate ER stress may include 
			the use of chemical chaperones and unfolded protein response enhancers (gene therapy or small molecules).

| Open Graph in a new window |

Fig 1. Peripheral neuropathies and endoplasmic reticulum (ER) stress-mediated therapies. (1)
Courtney C. Babbitt, Lisa R. Warner, Olivier Fedrigo, Christine E. Wall, Gregory A. Wray, Published 22 December 2010

What we know ...

  1. Advanced Glycation End-products (AGEs) impede the supply of cholesterol, fats, and oxygen transport to neurons. A diet high in processed carbohydrates and low in fats results in AGEs. This leads to cholesterol deficiency in neurons, which significantly impairs their ability to function. (A) (Note 1,2,3)

    Dr. Seneff ... Over time, a cascade response leads to impaired glutamate signaling, increased oxidative damage, mitochondrial and lysosomal dysfunction, increased risk to microbial infection, and, ultimately, apoptosis. Key.

  2. The decline of Myelin and neuronal membrane integrity is a loss of Oligodendrocyte and Schwann cell integrity. The cholesterol in the myelin is highly susceptible to oxidation damage and the depletion of cholesterol leads to loss of both myelin and membrane functions. Recent population studies have confirmed a correlation between low blood serum cholesterol and both dementia and Parkinson's disease. (A)

    Myelin is a fatty material that coats, protects, and insulates nerves, enabling them to quickly conduct impulses between the brain and different parts of the body. Myelin also contains proteins that can be targeted by the immune system.

  3. Late-stage Alzheimer's disease: neuronal apoptosis. AD may be caused by a deficiency in the supply chain of cholesterol, fats, and antioxidants to the brain. Insufficient cholesterol, cholesterol sulfate, and fatty acid would also impair myelin sheath repair. A LCHF-ketogenic diet has been found to be therapeutic in AD patients [Costantini et.al., BMC Neurosci 2008] [Nicholson, Neuroscience 2008]. It involves an extremely high fat diet, with up to 88% of calories derived from fats. (B)
  4. Elderly Centenarians - have reduced capillary density, so Stress i.e. Exercise, is important to Angiogenesis and the pathways integral to aging. These pathways intersect with and modulate those regulating angiogenesis which evolved to support growth. Without stress we downregulate the growth of blood vessels in less active tissues. (B - Figure 2)

    Because the elderly are at higher risk for ischemic injury and other diseases in which angiogenesis is crucial to the healing response, this impairment increases end-organ damage and contributes to adverse clinical outcomes in the elderly. (C)

  5. Neural Receptors - are on the cell surface and are protein structures. Cell wall integrity is critical to neurons and neural function as this functioning is directly connected with marine Omega-3 fatty acids DHA and EPA. These fatty acids and Vitamin D, along with cholesterol keep the cell membrane healthy. If not ... cells that have bad structures to not support a healthy neural network. [Patrick RD, et al, 2015] (D)
  6. ... Ok Now What? - Repairing neural dysfunction.

    ... Ok - 2 nd Now What? - Immediate simple solutions.

 


 

Peripheral Nervous System | Malfunction = Neuropathy

Peripheral neuropathies refer to a group of conditions in which the peripheral nervous system (PNS) is damaged. These pathological states are associated with weakness, pain, and loss of motor and sensory control. More than 100 types of peripheral neuropathies have been identified, with distinct symptoms and prognosis classified according to the type of damage to the nerves.

Peripheral neuropathy distorts and sometimes interrupts messages between the brain and the rest of the body. Because every peripheral nerve has a highly specialized function in a specific part of the body, a wide array of symptoms can occur when nerves are damaged. A common first indicator is the tingling in the fingers and toes and the inability to sense pressure or temperature in the feet. Diabetic peripheral neuropathy (DPN) is a primary cause of ulcers and eventual amputation of digits or even whole limbs. (1,1a,1b)

1st - First Clue:  In the PNS, nerve injury triggers a response known as Wallerian degeneration with many root causes. (Note 1) Mitochondria play a central role in the survival and death of neurons. (2) The diagram - Fig 1, allows us to draw some conclusions and if we follow pathway A we see that a preventable injury to the nervous system is caused by diet. We know that "alcohol" follows the same pathway as "sugar", diabetes can be controlled or cured by a LCHF diet, and the autoimmune diseases in general are a direct result of the Refined-Carbohydrate Disease. (3)

Half of what we know is wrong, the purpose of science is to determine which half " ... Arthur Kornberg, Nobel Laureate - DNA, "The Nobel Prize in Physiology or Medicine 1959"

2nd - Second Clue:  this is "No Clue" as doctors call this Idiopathic and that of the estimated 50% of patients with nerve damage, doctors have No Clue as to why. Dr. Todd Lavine, gives a good overview of neuropathy and possible causes in his 2012 Webinar. (4)

Neuropathy and peripheral nervous system damage in aging 3rd - Third Clue:  nerve damage is the loss of myelin and the inability or slowdown of the PNS to transmit signals. Nerve signals are electrical and chemical processes. This simply means that the blood flow to nerves is critical, and that the blood must carry all of the oxygen, vitamins, and minerals plus proteins and fats to maintain electrical ionic states and the chemical pathways. Nutrients must "Get to the Cells".

Lipids and lipid metabolism have been linked to many disorders, both somatic - (Wiki), and neuropsychiatric i.e. brain-farts. In myelination disorders, the deficient myelin sheath does not properly insulate the axon, so transmission of nerve impulses is impeded. (5,5a,30)

  1. Neuropathy and peripheral nervous system damage in aging The endoneurial channel (Wiki) is the layer of connective tissue around the myelin sheath, and this nerve fiber has its own blood vessels running within the sheath.
  2. Endoneurial hypoxia may arise from small blood vessel occlusion, impaired diffusion and endoneurial capillary disease. The reduction in nerve blood flow in diabetic neuropathy is due to an increase in resistance to flow which may be due to microangiopathy (Wiki) and to blood hyperviscosity. This is more complex than sugar-alcohol accumulation in nerves. (6) Bad Blood = No Oxygen and Nutrition = Dead and Dying nerve.

    Neurobiology, ... hypoxia per se will reproduce the lipid biosynthetic and electrophysiological abnormalities (Yao and Low, 1986) (Low et al., 1985b). Low showed that creatine phosphate, the storage form of adenosine triphosphate (ATP), was significantly reduced in this endoneurial pathway as a response to microangiopathy and hypoxia (i.e. low Oxygen - O2).

    Neuropathy and peripheral nervous system damage in aging

    ATP levels are unusually stable even in working muscles due to several ATP-buffering systems such as creatine phosphate. The equilibrium between creatine, creatine phosphate, ADP and ATP is maintained by the body. Thus small changes in the ATP/ADP ratio are quickly evened out by use of creatine phosphate.

  3. It has been shown that Type 2 Diabetes can restrict these capillaries. The constant state of "Chronic" inflammation affects all body functions. The body's extremities suffer the most. i.e. What goes first when cold? Your body protects its core.
  4. Vascular dysfunction and the Na+/K+ ATPase ion transporter, which is a critical functioning part of every animal cell, and plays a major roll in cellular malnutrition and dysfunction. (6a) This dysfunction of the Potassium-Sodium pump is discussed as part of the Heart's Electrical System and Abnormal Rhythms | contributor/2016.
  5. Hypothesis: there is evidence that "Cholesterol deficiency" coupled with not enough actual sun and hence a vitamin D deficiency, and with a deficiency in sulfur, defeats the purpose of cholesterol and Cholesterol-Sulfate as a metabolic agent and an energy source for the body. The body will pull/steal sulfur from the Myelin sheath and Collagen in the Joints. Consequently the body has activated the "Triage Theory" and put it to work. This water soluble active form of cholesterol "Cholesterol-Sulfate" is involved in the same 2,000 gene expression pathways as vitamin D. Nerve damage modulation and meylin repair is one of these functions. (7,8)

Neuropathy, longevity, and peripheral nervous system damage in aging Key Knowledge: You are turning off your immune system with a poor diet. The body favors short-term survival over long-term health. This trade-off accelerates aging-associated diseases, such as cancer, cardiovascular disease, immune dysfunction, and cognitive decline.

High carbohydrate diets shut down the body’s own antioxidant defense genes which are far more powerful than any supplement you can take.

 

Endoplasmic reticulum (ER):  endoplasmic reticulum is a dynamic interconnected network involved in quality control processes that maintain a functional proteome in the cell. (Note 4) The ER contributes to local calcium homeostasis, lipid synthesis and translation, folding and secretion of proteins, among other metabolic functions. Accumulating evidence indicates that CNS and PNS injury alters ER proteostasis engaging a stress reaction in neurons and glial cells (1,10) (Note 5)

Neuropathy, longevity, and peripheral nervous system damage in aging Oligodendrocyte (Wiki) cells are a type of glial cell that is involved in the production of myelin, providing support and insulation to axions in the central nervous system. A single oligodendrocyte can extend its processes to 50 axons, wrapping approximately 1 p (micro-meter) of myelin sheath around each axon.

Dr. Panda's Time Restricted Feeding - TRF or Dr. Longo Fasting-Mimicking Diet (FMD) and Fasting have been shown to reverse damage to the myelin. Studies on TRF and FMD (i.e. some form of fasting cycle) holds promise in treating autoimmune disease. Triggering Apoptosis - (Wiki) allows the immune cells to die and be replaced by new immune cells in MS. (11,11a)

Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. FMD also stimulated remyelination and regeneration of oligodendrocytes. (12,13) i.e. our bodies really do need "Repair Time and it is a Function of our Metabolism".

Millions of cells are replaced every second, and estimated 300 billion cell per day die and are replaced. The role of apoptosis in normal physiology is as significant as that of its counterpart, mitosis - (YG). (Note 6) It demonstrates a complementary but opposite role to mitosis and cell proliferation in the regulation of various cell populations. It is estimated that to maintain homeostasis in the adult human body, around 300 billion cells are made each day just to balance those dying by apoptosis.

The Fasting - Re-Feeding cycle, as proposed by Dr. Valter Longo - USC Longevity Institute, triggers many beneficial genetic responses. (Ref: Day 1 ... the Centenarian Diet) This is not just fasting, as the "Re-feeding" is important to the genetic response for repair and rebuilding metabolic pathways. However, this is where all nutrients are needed to avoid the "Triage" response. (14) i.e. "... Bad Nutrition = Bad Blood = Bad Metabolism".

The mechanistic machinery of apoptosis and mitosis is vital because programmed cell death and rebirth is a component of both health and disease. The available nutrients and the body's allocation of resources controls metabolism. There are "Many" nutrient sensing - (Wiki) pathways and all this machinery depends on diet. Ref: ... Nutrigenomics and Epigenetics | contributor/july-2016

 

Central Nervous System | Malfunction = Death

The central nervous system (CNS), comprising the brain, spinal cord, and retina, is the control panel for our bodies. This control mechanism is responsible for cognition, movement, senses, and emotions. CNS diseases include neurodegenerative diseases, neurodevelopmental diseases, and traumatic injuries.

With only a limited capacity for self-repair and few biomolecules on the market to treat those with CNS diseases/disorders, the options for patients are grim, yet the opportunity to make a difference palpable. Regenerative medicine offers hope to patients, using neuroregenerative and/or neuroprotective strategies. (21)

Most systems and organs of the body control just one function, but the central nervous system does many jobs at the same time. It controls all voluntary movement, such as speech and walking, and involuntary movements, such as blinking and breathing. It is also the core of our thoughts, perceptions, and emotions.

 


 

Ok - Now What? | Repairing Neural Dysfunction

Can Nerve dysfunction be repaired ? and how ?

We want Neurogenesis - and there are many metabolic pathways that can do this. Exercise is one of them as it is shown to increase Telomerase activity and Neurogenesis.

Neuropathy and peripheral nervous system damage in aging

| Open Graph in a new window |

StemCells™ - Oligodendrocyte forms healthy Myelin Sheath (30)
Activating - our own progenitor Stem Cells
Oligodendrocyte
Normal transmission of nerve impulses.

The peripheral nervous system (PNS) differs from the central nervous system (CNS) in that it is capable of remarkable regeneration even after severe injury. After an injury, both PNS and CNS axons distal to the lesion degenerate, but only PNS axons regrow and reconnect to their targets. The distinct ability of peripheral nerves to regrow back to their targets hinges on the regenerative properties of its glia, the Schwann cells. (31)

The Good News is that we have stem cells throughout our body that differentiate into new cells during our body's repair cycle. And, nerve tissue, can be repaired by the body. Schwann cells retain a high degree of plasticity throughout adult life and upon injury shed their myelin sheaths and dedifferentiate en masse to a progenitor/stem cell-like state. (32)

The Not So - Good News is that this falls into the Clue 2 category, "Idiopathic" with little known solutions.

However, unlike nerves of the spinal cord (CNS), the peripheral nervous system has regenerative capabilities. PNS nerves are able to reconnect and re-establish their function. This makes evolutionary sense, otherwise, every time we had a serve cut or bone break we would lose control of that appendage.

Schwann cells are important players in this process, during which they dedifferentiate to a progenitor/stem cell and promote axonal regrowth. (32,32a)Fibroblasts (a well-studied cell type known to play a role in wound healing) send a signal to the Schwann cells, causing them to sort themselves into clumps, or cords, that make their way out of the nerve stump as a group. Those cords guide the regrowth of axons across the wound.

Caveat - our first concern must be the removal of the "Cause" of the dysfunction (Axonal degeneration) if we would like our body's repair mechanisms to response. i.e. Smoking, excess Alcohol, excess Proteins, High Carbohydrate eating and Low Nutrient intake (i.e. Chronic Inflammation), as a remedy to live to 100, we propose ... this site - the Centenarian Diet. (33,33a)

As Seen on TV - Diabetic and other neuropathies affect predominantly small myelinated and unmyelinated fibers that convey pain and temperature sensation. Degeneration in these "small fiber neuropathies" involves the most distal portions of nerve fibers that are found in different organs and tissues (somatic fibers) rather than fibers in major nerves. It has been show that this is a direct result of Chronic Inflammation (Medically - inflammatory demyelinative polyradiculoneuropathies) and hence diet ... the Obesogenic Diet which can be avoided. Will power and the desire to live past 100 is the issue ... Avoid Chronic Inflammation, because you ... cannot Get to the Future Sick.

Dr. Patrick's Video on

Hyperthermic Conditioning for Hypertrophy, Endurance, and Neurogenesis - Apr/2014

FoundMyFitness.com - Dr. Rhonda Patrick

From News - Medical Life Sciences, Hormone prolactin key to repairing nerve cell damage, a team of researchers from the U of C's Faculty of Medicine reports that a study found that the hormone prolactin encourages the spontaneous production of myelin.Tthe study is the first to determine that prolactin, is directly responsible for the formation of new myelin in the brain and spinal cord. This study was done for MS research. MS is a neurodegenerative disease where the body's own immune system attacks the myelin surrounding nerves.

Dr. Fred (Rusty) Gage, of the Salk Institute says, Agents promoting remyelination will be beneficial not only for typical demyelinating diseases like MS, but also for many other neurological disorders, such as spinal cord injuries and stroke. Gage, an international leader in nervous system repair.

For the readers, do your own ... Research on Age-Related Neurodegenerative Disease - Prolactin and Myelination.

 


 

Ok - 2nd Now What? | Immediate Simple Solutions

Any Hope: (Onate, Court, and Hetz, 2016) (1) of successful axonal repair depends on intrinsic capacities of neurons and the reaction of glial cells and micro-environmental factors that modulate the regeneration process. Peripheral neuropathies are triggered by a large spectrum of conditions, representing a serious public health problem. Only in the United States it is estimated that 20 million people are affected with peripheral neuropathies.
Q : Is it possible that Micro-environmental factors = Nutrition?.
Q : Is this Carbohydrate Sensitivity? ... the understanding as yet TBD, and from contributors ... Carbohydrates and Longevity | contributor October/2016.

The current issue is that everyone responds differently to Carbohydrate Sensitivity → Intolerance. Hence, we see people that can use Sugars and many who develop chronic inflammation and autoimmune diseases. Ref: ... Insulin Resistance.

Exercise ... is Good Stress, so avoid a sedentary lifestyle and avoid the Colloquial Tag - Couch Potato. The body has three to six (3-6) principle circulatory systems, depending on definitions and All require muscle movement to function. → Cardiovascular - Heart, → Pulmonary - Lungs, → Systemic -Blood and Vessels, moved by our involuntary muscle system.

The Lymphatic - Lymph, requires our voluntary muscles to contract and provide circulation, i.e. ... movement and Exercise. The Endocrine - Hormones are driven by metabolic chemical signals, with the Guts and Gut Microbiome - Manufacturing and Recycling, communicating with the body's WBR - Whole Body Requirements.

Simple solution, avoid carbohydrates as they offer No known nutritional benefits. Carbohydrates are however packaged in food source organisms that do provide Longevity Vitamins, Our foods provide Phytonutrients, macronutrients, micronutrients (for critical DNA repair) (R1), Polyphenols, Phytosterols, Flavonoids, Lignans, Antioxidants, and Carotenoids, that do allow life to continue. Ref: 100 richest dietary sources of polyphenols. (Resource 1,2,3)

Certainly avoid "Don'ts" - processed carbohydrates, fats and oils, and any packaged foods. A direct result of too many carbohydrates is Insulin Resistance functional manifested as Carbohydrate Intolerance. Dr. Volek discusses his current views on the benefits of a LCHF plan - Health-Promoting Effects of a Low-Carbohydrate Lifestyle | july/2016 and this site follows this type of plan with the addition of Dr. Ames' "Triage Theory" by proposing ... the Centenarian Diet.

 


Notes:

  1. Glycation - Advanced Glycation End Products (AGE’s), "fast carbs" (refined and high glycemic index carbohydrates) raise blood sugar levels, and excess blood sugar can bind to vital proteins, DNA, RNA, and fats in the body and damage them, sometimes beyond repair. This process is called “glycation”. Proteins are supposed to be able to fold and move in special ways to perform their various special functions, but they can’t do that if sugar is gumming up the works. When sugars bind permanently to proteins, they turn the proteins into nuisance compounds called “Advanced Glycation End Products” or AGE’s. AGE’s have been linked to a wide variety of chronic diseases, including heart disease, kidney failure, diabetic retinopathy, Alzheimer’s disease, and aging. (40)

    AGE - Defined, Advanced Glycation End-product, is used to describe any sugar-damaged protein. As we age, excessive amounts of free sugars in the blood may eventually cause damage quicker than the body can repair it. The sugars attach by a chemical reaction and the sugar called fructose is known to be 10 times more reactive, and therefore more dangerous than our normal blood sugar (glucose). (40a,b)
  2. Carbohydrates and Oxidative Damage is created when oxidants are out of balance. Fast carbs are “pro-oxidants.” This means that they have the power to damage important body molecules, such as DNA, by stealing their electrons away from them. Pro-oxidants are the opposite of anti-oxidants; they fight against each other. In a healthy body, pro-oxidants and the antioxidants are in balance.
  3. Carbohydrates and Inflammation, both glycation and oxidation trigger inflammation in the body. Physicians and scientists have come to understand that most common chronic diseases are rooted in inflammation.
  4. Wallerian degeneration, is characterized by axonal damage due to an increase in axoplasmic calcium, mitochondrial dysfunction and cytoskeleton breakdown, just to mention a known few causes. We know that Chronic Inflammation interferes with blood flow in the Peripheral body parts ..., hence, malnutrition to these parts, can be the primary cause of neuropathies. We have Malnutrition in a Land of Potato Chips and Frosted Flakes - Who Knew. Ref: ... the Obesogenic Diet. and (41,41a)
  5. The entire complement of proteins that is or can be expressed by a cell, tissue, or organism. Now that the human genome has been deciphered, much of the fanfare surrounding it has transferred to the proteome. The Human Proteome Map - HPM (42)
  6. YG, yourgenome.com - yourgenome is the place for you to find out everything you want to know about DNA, genes and genomes. From the basic biology to the challenging ethical issues, it’s here for you to discover and explore! YG Facts - What is DNA? What is a Gene?

 


[ + ] Sources and References:

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  3. B Circulation Reserch, 2012, Effects of Aging on Angiogenesis, Johanna Lahteenvuo, Anthony Rosenzweig, David Sinclair and Brian North.
  4. C ALCOR, Life Extension Foundation, The Pathophysiology of Ischemic Injury, by Mike Darwin, BioPreservation, Inc. (1995)
  5. D FAB - FASEB 2015, Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar, schizophrenia, and impulsive behavior. Patrick RP, Ames BN
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