Ketosis, from any source, Improves Memory By Providing Beta Hydroxybutyrate

Interesting and pointed scientific finding below!  Note that delayed exercise 4 hours after learning improved consolidation.  Why? How?

Exercise raised DBHB or beta hydroxybutyrate which inhibited histone the chemical that switches off the BDNF gene increased by learning or metabolism of hippocampal brain cells during learning.  Raising BDNF during the later consolidation period allowed greater transfer or consolidation by the cortex.  BETA HYDROXYBUTYRATE INCREASES BDNF!

Therefore exercise related ketosis, fasting related ketosis, lower carbohydrate diet, weight loss, coconut oil or medium triglyceride oil INCREASE BDNF via increased levels of beta hydroxybutyrate!

Review:  BDNF increases and improves Memory, Mood and Metabolism.  Depression is associated with low levels of BDNF resulting in depressed mood and cognition.  Cognition lags mood improvement in depression treatment with medications.  Exercise and slow paced breathing when added to antidepressant therapy improved depression score by 42%.  Shouldn't cognition also be improved?  Exercise increases BHB to raise BDNF.  Slow paced breathing reduces brain cortisol that inhibits BDNF production and results in higher levels of BDNF.  Higher BDNF improves cognition and depressed mood.

Beta Hydroxybutyrate promotes genes that increase BDNF that improve Memory, Mood and Metabolism from whatever source.

http://www.kurzweilai.net/need-to-remember-something-exercise-4-hours-later 

Low Carb Diet, Intermittent Fasting and Exercise Reduce Inflammasome

Thought the details of this paper and the elegant study of inhibiting the innate immune system by blocking 2 of 3 components of the inflammasome specifically NLRP3 and Caspase, with ketones or BHB beta hydroxybutyrate were profoundly important.

Inflammation is associated with aging, metabolic syndrome and autoimmune disorders.  It has also been implicated in depression and dementia.

Either through lower carb diet with interval intermittent fasting and/or exercise related ketosis one can raise BHB to low but inhibitory levels that block or prevent inflammation, aging, metabolic syndrome,autoimmune disorders, depression and dementia.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4817415/pdf/ctg20166a.pdf

PPAR gamma and the Health and Resilience of Mammalian Cells and Organisms

What formula explains the health of the mammalian cell and the mammalian organism?  My view is the following.

Wealth plus Wages minus Expense.

Health plus BDNF (a bio marker of cell and organism plasticity produced in brain and blood vessels)  minus Inflammasome activity.

How can one reduce the cost and inflammation of living and aging? The study below illustrates a tactic based on the above strategy.

This study, and others, show that increasing  ppar gamma reduces the inflammasome resulting in more health and greater resilience.  In this study less depression resulting from chronic mild stress.  Depression could be substituted for cognitive impairment, dementia, diabetes, hypertension or atherosclerosis if they share a common cause or cellular innate inflammation, activation of the inflammasome consisting of NLRP3, interleukin 1 beta and Caspase.

 Ppar gamma activity inhibits 2 of 3 components of the inflammasome, NLRP3 and interleukin-1b which reduces pyroptosis and apoptosis - cell on fire and cell death!  In effect, ppar gamma shifts cells to be free of inflammation and to have abundant energy needed to remain young and resilient.

Ursolic acid and now Apigenin have been proved to drive ppar gamma and promote youthful resilient cells.  This would be helpful for age related degenerative disease, autoimmune diseases and substance related neuroinflammation damage.

A simple experiment would be Ursolic acid 200 mgs (Amazon/Labrada) three times daily for 8 weeks and measuring targets of metabolic syndrome; blood pressure, triglyceride, fasting insulin, glucose, high sensitivity CRP,Homo-IR,  waistline change, mini mental exam, depression questionnaire, 6 minute walk/run distance, VO2 max, exercise to exhaustion , HgbA1c, BDNF or heart rate variability index.

Apigenin ameliorates chronic mild stress-induced depressive behavior by inhibiting interleukin-1β production and NLRP3 inflammasome activation in the rat brain — ScienceDirect

http://www.sciencedirect.com/science/article/pii/S0166432815302047

Abstract

Increasing evidence suggests that inflammation and oxidative stress may contribute to the development of major depressive disorder (MDD). Apigenin, a type of bioflavonoid widely found in citrus fruits, has a number of biological actions including anti-inflammatory and antioxidant effects. Although apigenin has potential antidepressant activity, the mechanisms of this effect remain unclear. The present study aims to investigate the effects of apigenin on behavioral changes and inflammatory responses induced by chronic unpredictable mild stress (CUMS) in rats. GW9662, a selective peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor, was administered 30 min before apigenin. We found that treatment with apigenin (20 mg/kg, intragastrically) for three weeks remarkably ameliorated CUMS-induced behavioral abnormalities, such as decreased locomotor activity and reduced sucrose consumption. In response to oxidative stress, the NLRP3 inflammasome was activated and IL-1β secretion increased in the prefrontal cortex (PFC) of CUMS rats. However, apigenin treatment upregulated PPARγ expression and downregulated the expression of NLRP3, which subsequently downregulated the production of IL-1β. In addition, GW9662 diminished the inhibitory effects of apigenin on the NLRP3 inflammasome. In conclusion, our results demonstrate that apigenin exhibits antidepressant-like effects in CUMS rats, possibly by inhibiting IL-1β production and NLRP3 inflammasome expression via the up-regulation of PPARγ expression.

Joseph Thomas (Tony) Liverman,

Reducing Addiction a Network or Sociological Framework

Greetings. Thought you might be interested in the following:

1: a sociological insight from network theory from article below, and

http://www.kurzweilai.net/hierarchies-exist-in-the-brain-because-of-lower-connection-costs-research-shows

2: an effective tool to overcome the costs of addiction from a brain plasticity program that explicitly reduces the "cost of connection."

Network theory is increasingly a better model of sociological structure and resilience than power submissive or dependent relationships.

It occurs to me that the "costs of connection/relationship" is also important in shaping hierarchies in society.  Resilience requires dissipative forces that spreads out costly connections in order to preserve the most functional network formation possible.

Rehabilitation programs are a positive dissipative force to allow the best relationship possible to the network UNTIL the "cost of connection" decreases and allows a fuller stronger relationship.  I believe it is possible, due to brain plasticity, for "costly connections" to evolve into "lower cost connections."

In other words, when one can develop a better central executive center in the forebrain, make better choices and profit from  those choices,  one may rise in hierarchy and decrease in costs within the network.

BDNF or brain derived neurotrophic factor is a bio marker of change.  The greater the BDNF, the greater the resilience against addictions of all kinds.  Specifically opiate addiction is a low BDNF state early and late in recovery.  After 26 weeks of abstinence BDNF levels are below average and resilience is also below average.  Moreover impulsive behaviors and attention deficits are inversely proportional to BDNF levels in peripheral blood.

Take home message:  Increase BDNF, reduce addictions and increase resilience.

How?

1.  4 minute high intensity interval session daily. Tabata timer for smart phone.  Jump rope 20 seconds and stop for 10 seconds and repeat 8 times.

2. 2 minutes of slow paced breathing 5 seconds in and 5 seconds out twice daily.

3.  Weekly 24 hour fasting.  One can drink diet beverage or coffee with cream and artificial sweetener.  

4.  BrainHQ.com. Brain training to increase brain network speed.

5.  Ursolic acid 200 mgs with meals three times daily.  Amazon, Labrada brand

6.  Melatonin 3 - 10 mgs at 9 pm.

All of the above is associated with increased BDNF and greater resilience.  I believe it is a scientifically validated means to reduce addiction and promote a full recovery and restore resilience.

Hierarchies exist in the brain because of lower connection costs, research shows

http://www.kurzweilai.net/hierarchies-exist-in-the-brain-because-of-lower-connection-costs-research-shows

Review Article on Aging Theories, a Synthesis

Aging is both replicative and stress related.

Mitochondrial energetics is involved in the signaling that slows replication and repair related aging.

Telomerase and telomeres are markers of replicative aging directly and stress related aging indirectly.  The telomeres are copied as mRNA and in mitochondria promote antioxidant production by the mitochondria (if adequate energy or ATP is present.)

Stress such as exercise, rapid growth or calorie restriction is an indirect antioxidant stimulator.  Stress that promotes versus stress levels that signal deterioration and the quality of recovery determines the net effect of resilience building.

The heart rate variability index gives feedback to the direction of aging resilience.

Greater heart rate variabilty index is greater resilience.  It correlates to bio markers of repair and regeneration such as BDNF, mitochondrial and organism ability to metabolize lipids and increase endurance exercise performance.

Increased heart rate variability is a network marker of stress levels that promote antioxidant capacity from stress levels that deteriorate and use up antioxidant capacity.  Eg.  Sepsis signals deterioration level stress 70 hours ahead of overwhelming neonatal sepsis.  In effect there is no return to baseline or elevation of baseline after sleep or recovery interval of rest!

The neuro-endocrine-cardiac network is incrementally plastic.  There are many lifestyle, dietary and supplement strategies to nudge the cell and the collective network of cells towards reversing or regenerating the changes of aging.  

There is also evidence that genetically enhancing telomerase and lengthening telomeres in cells reverses aging changes inclusive of replicative and oxidative stress.

Therefore aging is binary; active and resting, stress and recovery in a balanced way.

If one promotes slow aging, one reduces reproductive capability.

If one promotes faster aging, one promotes reproductive capability.

What is missing in studies of lifestyle, diet and supplements that concluded the above is balance or circadian daily rhythm.  Recovery and greater resilience is the response to lifestyle, diet or supplement stress or reduced stress.

I have previously discussed the indirect and direct antioxidants.  Indirect is physical or nutritional stress that promotes increased cellular antioxidant capacity such as exercise or calorie restriction. Direct antioxidants are exemplified by melatonin during recovery or telomere mRNA effects of youth related growth and replication stress adaptation.

If direct and indirect are used simultaneously they weaken one another.  If used sequentially they augment each other.  In effect the signal to become more resilient to stress is followed by rest of metabolic stressors during sleep and recovery.  The gain is not spent returning to the old baseline but growing beyond the baseline.

http://file.scirp.org/pdf/AAR_2016031710133706.pdf

Ursolic Acid for Neurodegenerative Disease

Ursolic acid, a supplement from Apple peels, rosemary and thyme, is a peristome proliferator- activated receptor gamma that is neuroprotective and increases the metabolism of triglycerides into beta hydroxybutyrate, the ketone body metabolite derived from coconut oil and MCT oil.  This both protects, provides additional alternative brain energy substrate and increases mitochondrial biogenesis or greater metabolic factories for the cell.

Available at Amazon.com or Labrada.com.

Highlights

• •
  Mitochondrial dysfunctions contribute to the pathogenesis of Parkinson's disease (PD).
• •
  PPARγ is a transcription factor with metabolic functions in the body.
• •
  PGC-1α is a master regulator of mitochondrial biogenesis and cell viability.
• •
  PPARγ agonist increased PGC-1α and cell respiration in human dopaminergic neurons.
• •
  PPARγ agonist increased the phosphorylation of CREB and AC6 levels in the neurons.
  
  

http://www.sciencedirect.com/science/article/pii/S0028390815301842

Abstract

Mitochondrial dysfunction has been linked to several neurodegenerative diseases such as Parkinson's disease (PD). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master gene for mitochondrial biogenesis and has been shown to be neuroprotective in models of PD. In this work we have studied the mechanisms by which peroxisome proliferator-activated receptor-γ (PPARγ) selective agonist N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino)ethyl]-l-tyrosine hydrate (GW1929) acts on human dopaminergic neurons in culture. Data showed that GW1929 increased the viability of human dopaminergic neurons and protected them against oxidative stress induced by H₂O₂ and the mitochondrial toxin Rotenone. The enhanced resilience of the neurons was attributed to increased levels of mitochondrial antioxidants and of PGC-1α. GW1929 treatment further increased cell respiration, mitochondrial biogenesis and sirtuin-1 (SIRT1) expression in the human dopaminergic neurons. Phosphorylation of cAMP responsive element-binding protein (CREB) was also robustly increased in GW1929-treated cells. Together these results show that the PPARγ agonist GW1929 influences CREB signaling and PGC-1α activities in the human dopaminergic neurons contributing to an increased cell viability. This supports the view that drugs acting on the PPARγ-PGC-1α signaling in neurons may have beneficial effects in PD and possible also in other brain disorders.