Cellular, Organ and Organism Level Network Resilience

This article explores the importance of a system resilience in maintaining health and function.

The cell is a network.  The body is a network.  The cell, organ and organism must have similar systems of resilience.

Conceptually every system has an accelerator and a braking system to remain stable.  

Dysfunction precedes loss.  

That is why resilience systems are vital.  BDNF and HRV heart rate variability are likely at the core of resilience.  They decline and predict system failure in cells, organs and organisms.

A midlife sympathetic tone dysfunction precedes cognitive, mood and body decline by 20 years.  Those who delay this decline maintain memory, mood and metabolism or system resilience.

We do not know what the limits of these hormetic or resilience actions, but they are substantial and worth participating in a healthy lifestyle.

HRV is proxy for this resilience.  I plan to measure my resting heart rate variability with a a $50 Bluetooth heart rate monitor and IPad app to calculate.  I hope to be able to demonstrate that lifestyle efforts to raise BDNF will increase HRV and by extension resilience and health; improved memory, mood and metabolism; reduced mortality.

The Trajectory of Life.  Decreasing Physiological Network Complexity Through Changing Fractal Patterns.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451341/pdf/fphys-06-00169.pdf

Brain Network Function improved by Higher BDNF relative to Klotho Variant Status

Here in abstract below is the evidence for the Klotho gene variant rs1207568 homozygous requiring highest levels of BDNF, the absence of Klotho gene variant requiring intermediate levels of BDNF and the heterozygous Klotho variant require lower levels of BDNF to have normal mood (and cognition.)

"we confirmed a significant improvement of depressive symptoms after treatment in patients carrying at least one minor allele at rs1207568 and a worse response in patients homozygous for the minor allele at rs9536314. Our results were the first that suggested a possible role of KL in the complex pathway of SSRI response in late-life MDD."

Klotho polymorphism affects SSRI response in late life depression.

GT. high response.

TT  normal response

GG. Low response.

Klotho gene /normal gene as heterozygous pair amplifies BDNF effect via GluN2b receptor increase.  Absence of this amplifier status for BDNF then requires more BDNF to achieve an antidepressant response in TT homozygous normal gene and even higher BDNF levels for homozygous GG.

Hence my statement,  all patients need BDNF but some need it more is confirmed.  Depression is a low BDNF state.  SSRI work to increase BDNF levels.  Response to SSRI is therefore a function of Klotho variant gene status and BDNF level achieved with treatment.

The addition of lifestyle to optimally raise BDNF will improve response rates above SSRI alone.  Higher BDNF levels further improve mood, memory and metabolism.

http://link.springer.com/article/10.1007/s12035-016-9711-y

Two BDNF Producing Activities are Better , How about Five or More?

This abstract shows that exercise and cognitive brain gaming improved cognitive function in older individuals.

I believe this verifies that exercise and cognitive training increases BDNF more than exercise alone , improving cognition/memory, mood and metabolism.  A proxy for serum BDNF level is heart rate variability which is a function of noradrenalin produced during exercise of both body and mind and its effect on Vagal neurons that promote greater heart rate variability. 

This partially answer the question, would other combinations of lifestyle changes increasing BDNF be synergistic resulting in greater improved memory, mood and metabolism and its proxy resting respiratory heart rate variability?

I think this will be proved! 

 Conjecture:  resting heart rate variability will become a measurable proxy for BDNF and prevent overtraining due to over exertion or age related intolerance in persons of all ages.

http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=10033638&fileId=S1355617715001083

Journal of the International Neuropsychological Society

Aerobic and Cognitive Exercise (ACE) Pilot Study for Older Adults: Executive Function Improves with Cognitive Challenge While Exergaming

Nicole Barcelos^a1, Nikita Shah^a1, Katherine Cohen^a1, Michael J. Hogan^a2, Eamon Mulkerrin^a3, Paul J. Arciero^a4, Brian D. Cohen^a1, Arthur F. Kramer^a5 and Cay Anderson-Hanley^a1 

BDNF; Aging and Anti-Aging

Noradrenalin up regulates the Muller cell ( a retinal glial or helper cell of retinal nerves and nerve endings) production of BDNF (brain derived neurotrophic factor). Retinal degeneration occurs in elderly persons, the same age group cohort that develops other neurodegenerative diseases that BDNF prevents.

Noradrenalin is produced in high levels by HIIE (high intensity interval exercise.)

An early defect, preceding Alzheimer's disease by 20 years, is intracranial sympathetic (noradrenalin) tone loss that is associated with reduced heart rate variability, low BDNF levels and lower aerobic exercise capacity.  

Increased BDNF level, especially associated with noradrenalin increase, should protect the retina and brain.  HIIE of 4 minutes increases noradrenalin by 17 fold and last 19 minutes post exercise.  The use of green tea extract, an o methyl transferase inhibitor (enzyme that degrades stimulants) prolongs the basal (resting) rate of noradrenalin and may also be helpful.  Lastly, endothelial (blood vessel lining cells) cells produce BDNF, and taste bud receptor cells produce BDNF and is responsible for the continuous synapticity or connection hookup of the nerve to the taste bud.  Noradrenalin may up regulate the mRNA (DNA template that makes gene product proteins) of BDNF directly.  Green tea extract will be an indirect agonist (increases action) by increasing noradrenalin duration of activity by blocking its enzymatic break down.  HIIE would pulse or strengthen the effect of both.

Age related conditions are negatively impacted by BDNF neurodegenerative change.  

First in sympathetic and autonomic systems.  

Second in their end organs, 

retina, macular neuro-degeneration, 

taste, lack of connection or hook up of nerves to taste buds, 

appetite, a function of bone marrow produced BDNF, 

brain, mood and cognitive disconnection syndrome, and

heart, where low BDNF levels reduces the relaxation and contraction limits of the heart muscle cell and reduces the pump function of the heart reducing activity levels.

Conjecture.

Aging is degeneration of the network within and between cells.

Lack of BDNF allows degeneration.

Normal or increased BDNF reverses, stabilizes or slows degeneration.

A negative BDNF lifestyle and inflammation within cells and between cells degrades the individual's memory, mood and metabolism.

A positive BDNF lifestyle and anti-inflammatory strategy could reverse, stabilize or slow the disconnection syndrome that degrades the individual's memory, mood and metabolism. (Vision, hearing, taste, appetite, cardiac output)

Conjecture 2.

The elderly during and post autonomic, sympathetic intracranial nerve function decline might be rescued with supplementation of lifestyle agonist known to increase BDNF.

Noradrenalin; green tea extract, stimulant therapy.

Lactate; LR iv, Mag Lactate. (Lactate producing exercise increase BDNF production )

Intermittent weekly fasting; MCT oil. Axona to provide beta hydroxybutyrate.

HIIE; blood restricted exercise to produce lactic acid with low intensity exercise.

The core of this can be accomplished with my 3,2,1 plan at LivermanHealthAdvice.blogspot.com.

Müller Cells as a Source of Brain-derived Neurotrophic Factor in the Retina: Noradrenaline Upregulates Brain-derived Neurotrophic Factor Levels in Cultured Rat Müller Cells - Springer

http://link.springer.com/article/10.1007%2Fs11064-005-7936-7

Abstract

Müller cells, the predominant glial cells in the retina, are thought to play important roles in the survival of retinal neurons. Previous studies have demonstrated that Müller cells express brain-derived neurotrophic factor (BDNF), which has a pronounced neurotrophic effect on retinal ganglion cells. In this study, we investigated whether Müller cells express and release BDNF in culture. Reverse transcriptase-PCR, immunocytochemistry and Western blotting revealed that Müller cells produce BDNF mRNA and protein. Using the enzyme-linked immunosorbant assay, BDNF protein levels in Müller cells and their conditioned medium were quantified, demonstrating that Müller cells produce and release high levels of BDNF. Noradrenaline administration caused an upregulation of BDNF mRNA and protein expression by cultured Müller cells. These results suggest that Müller cells may act as an endogenous source of BDNF in the retina. Furthermore, induction of BDNF expression by adrenergic agonists may provide a therapeutic approach to retinal neurodegenerative disorders.

Other Bipolar Disorders, Anorexia Nervosa and Bulimia, Opiate and Stimulant Addictions

Here is an enlightened article showing how cognitive training (which increases BDNF, synapticity, nerve function and nerve cell integrity)  potentially allows better decision making by activating cognitive and salience networks via working memory and cognitive training.

This results in better choices, less denial and greater levels of BDNF (that has been shown to rise in 26 weeks of opiate addiction recovery to levels below normal controls).  Perhaps cognitive brain training will increase BDNF levels above normal and provide more resilience!  Perhaps other BDNF increasing lifestyle interventions would further improve central executive function, promote brain plasticity and result in above average serum BDNF levels establishing resilience against relapse and global improvement in performance status of mental, emotional and physical resilience in general.

A debate on working memory and cognitive control: can we learn about the treatment of substance use disorders from the neural correlates of anorexia nervosa? | BMC Psychiatry | Full Text

http://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-016-0714-z

Joseph Thomas (Tony) Liverman, Jr. MD 

Prevent and Reduce The Disease of Addiction; Increase BDNF, Treat Comorbidities

Conjecture: What perpetuates addictions is the following:

Addictions are begun by excitement, novelty and escape seeking.  The under 21 year old population is especially vulnerable because of developmental stage.  Those treated for pain and disability are vulnerable due to lifestyle changes that reduce BDNF.  Those who  experiment are vulnerable because opiates, and stimulants reduce BDNF.  So vulnerability to addictions are increased or decreased by BDNF levels.

Opiate Use and Depressant lifestyle change- reduces BDNF, leading to dysphoric mood and greater need to achieve escape velocity either up or down.

BDNF increases improve mood, memory and metabolism and reduces the need for escape velocity either up or down.

The desire to resume drugs for euphoria and escape remains inversely proportional to BDNF levels.

Some persons have "addictive personality" in proportion to their risks for dysphoric moods.  I.e. Bipolar patients.  See abstract below.

http://www.sciencedirect.com/science/article/pii/S0165032706001327

The evidence supports a lifestyle that increasing BDNF results in a better mood, better memory and better metabolism.  Less pain and less dysphoric mood reduces but does not eliminate relapse.  I am convinced, by the overwhelming evidence, that, the disease, addiction could be partially prevented or reduced by increasing BDNF before drug use and after treatment.

The options include:

Lifestyle alone.

Lifestyle plus supplements.

Lifestyle, supplements and nonnarcotic medications.

Lifestyle, supplements, nonnarcotic medications and opiate agonists.

Addiction would be treated like asthma.  Control the stage of disease and reduce therapy to the lowest cost lowest risk medication as determined by control.

In abstract below, Brain-derived neurotrophic factor serum levels are lowest after withdrawal rising but lower than normal controls after 26 weeks of abstinence.  The rise indicates successful treatment! and increasing resilience?  My conjecture states that lifestyle changes, supplements and nonnarcotic medications that raise BDNF levels above normal would increase resilience against addictions generally.

http://www.sciencedirect.com/science/article/pii/S0010440X15301139

Brain-derived neurotrophic factor serum levels in heroin-dependent patients after 26 weeks of withdrawal

Joseph Thomas (Tony) Liverman, Jr. MD

Implications of Klotho gene variant for BDNF Improving Memory, Mood and Metabolism

Implications of Klotho gene polymorphism for BDNF Improving Memory, Mood and Metabolism

Follow the bullets of the article linked below.  It depicts a bio marker of improved mood. BDNF which is only one of its three facets!

Bottom line-  differences in rate of learning, baseline mood and baseline physical performance can be greatly increased or optimized by increasing BDNF.  BDNF can be nick named 3M because it increases Memory, Mood and Metabolism.

Persons having only a single variant copy of the klotho longevity gene have increased memory associated with reduced mental loss with aging because of Glu2B amplification of nerve plasticity, an effect of BDNF.  Ergo it takes less BDNF to promote neurogenesis and network creation for learning and remembering in individuals and groups that have one copy of the variant Klotho gene and one common Klotho gene.

What are the implications of this finding?

It therefore follows that the rate of learning is strongest for individuals with one copy of variant gene or 23% of the population, average for 2 copies of the common Klotho gene and negative for two copies of the variant gene or 23% of the population.  This is a normal distribution of gene inheritance for a recessive gene that adds when one copy is present and subtracts when two copies are present.  As in Goldilocks 1 common and 1 variant gene copy is just right.  See GT, TT, GG at Klotho Rs9536314 on Wikipedia.  This is analogous to sickle cell inheritance with two variant copies having sickle cell disease, two normal copies having increased mortality to malaria and one copy of each being protective for malaria.

The NET effect of Klotho 2 gene variant status GG or 2 common gene status TT is poorer intellectual function and faster decline IN THE ABSENCE of HIGH or NORMAL BDNF.  To wit some depressed persons have greater memory and intellectual loss with low BDNF states or depression than others.

However, all persons would have greater Intellectual development and performance with higher levels of BDNF. Greater amplification of controlled synaptic activity and brain network development with higher levels of BDNF.  This is entirely analogous to cholesterol patterns in the population with the Mediterranean diet versus the American diet.  Ergo some persons are affected more or less by diet but all benefit from the Mediterranean diet.  Some persons are affected more or less by BDNF level but all persons benefit from higher or optimum levels of BDNF.

A lifestyle that promotes BDNF promotes the following:

Intellectual brain network development and speed.

Normal or improved mood

Improved mental, emotional and physical performance through time.

Resilience against addictions, opiates, gambling etc.

That lifestyle includes the following:

Weekly intermittent fasting to trigger expression of survival longevity genes including BDNF.

Slow paced diaphragmatic breathing for two minutes twice daily to reduce TNF alpha and brain cortisol levels thereby raising BDNF levels.

High intensity interval Tabata training or exhaustive lactate producing aerobic steady state exercise to maximally increase BDNF.

BrainHQ.com brain training to increase BDNF.

Raise BDNF with lifestyle, and when pathological mood disorders are present, medications to improve the entire person both memory, mood and metabolism.

This is clearly a shift the mean strategy for individuals and groups and has profound potential for education, healthcare, law enforcement and economics.

http://www.sciencedirect.com/science/article/pii/S002839081530157X