ANS the Autonomic Nervous System and Compassion for Self and Others; Golden Rule(r)

Why my 8 minutes can change your life blog post is relevant.

Why the podcast, though primitive in understanding physiology, was sent to my colleagues yesterday.

Because it represents two important legs or foundations of neuroimmune regulation.

Cardiac autonomic dysfunction (30-70% in chronic diabetes) has a 5x mortality rate with dysfunction rather than function!

Function requires feedback and positive and negative controls.

The controls are focused in brain stem,the locus ceruleus,where fast neurotransmitters/neuromodulators and slow neuropeptides (bdnf and gdnf) affect structure (imaging and pathology) and function (imaging and nerve function testing.)

Also hidden in the article is the word antidromic which means backwards nerve transmission.  This implies that nerve communication, though directional, actually goes both ways.

What does this have to do with daily hormetic doses of high intensity rest (vagal biofeedback breathing) and Tabata (high intensity interval feedback?

It strengthens and increases these chemical reserves and their responsiveness!

Consider shoulder pain secondary to tendinopathy.

Therapy stimulates a hormetic response that includes rest with progressive doses of exercise; isometric and passive motion, eccentric and passive and active motion, concentric and active followed by return to normal activities.  Brief hormetic doses to stimulate nerves and growth factors for healing.

It takes a minimum of six minutes to stimulate a healing response.

Therefore, promoting healing and recovery forces is medicine's mandate.  

The ANS is the systemic driver of healing for shoulders, brains and other organs.

In fact, the wandering vagus nerve, is the internet for compassion and healing both within and without.

Why not follow sage advice and exercise rest and therapeutic acute (not chronic) stress systems for enduring health, recovery and resilience?

https://n.neurology.org/content/92/8/377.abstract

Autonomic nervous system and neuroimmune interactions

New insights and clinical implications

Normal organ function, homeostasis, and adaptation through change (allostasis) require close reciprocal interactions between the autonomic and the immune systems. The 3 subdivisions of the autonomic nervous system—sympathetic, parasympathetic, and enteric nervous system (ENS)—as well as primary sensory afferents, receive signals from immune cells and release neurochemical transmitters that regulate the functions of these cells. These neuroimmune interactions occur at multiple levels, including the gut, the CNS, and lymphoid organs. For example, enteric neurons and glial cells interact with enteroendocrine cells and local macrophages and can sense signals from the gut lumen, including those from the microbiota; these signals elicit local immune responses and reach the CNS via humoral and neural pathways. Interleukins (ILs) and other signals from immune cells can access the hypothalamus via the neurovascular unit or circumventricular organs; these signals can also activate receptors in nerve terminals, such as vagal afferents, and thereby reach the brainstem. In response to these signals, the CNS initiates immunomodulatory autonomic and endocrine responses. For example, sympathetic output to lymphoid organs, including the spleen, elicits potent anti-inflammatory responses via β2 adrenergic receptors (adrenoceptors) expressed in multiple cells of the innate and adaptive immune systems. Vagal efferents affect immune responses in the gut via the ENS, and both vagal and dorsal root ganglion afferents trigger immunomodulatory responses via antidromic release of neuropeptides and other signals at the target organs. Since the last review on autonomic control of immune function in this series,¹ studies performed primarily on mice have provided new insight into the role of the microbiota, enteric neurons and glial cells, and autonomic immunomodulatory pathways in these neuroimmune interactions. These studies have elucidated some mechanisms by which these interactions may contribute to the pathophysiology of neurologic disorders including multiple sclerosis (MS) and spinal cord injury (SCI). These findings thus have potential therapeutic implications. There are several recent reviews on these topics.^2–12

Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the author, if any, are provided at the end of the article.

Joseph Thomas (Tony) Liverman, Jr.

Somatic and Stem Cells Health is Binomial and Reciprocal for Health and Longevity

Fasting mimicking diet reverses inflammatory bowel disease.

Note that this was superior to water only fasting.

Why?

Clean diet (fat burning) with Mediterranean supplementation with young cells containing Nrf2 drivers increased antioxidant enzyme status reversing disease in SOMATIC CELLS.  

Fasting improved regeneration and stemness in STEM CELLS.

I recommend a ketodiet, low carb high fat diet with Mediterranean supplements (wheat germ, nuts, olives, fruits and vegetables).

I recommend twelve or more hours of daily fasting.

Valter Longo endorses interval fasting mimicking diet in cancer treatment and cancer prevention.  This is another way of age (inflamaging) reversal which also improves "stemness".  This should be added at intervals on the above regimen.

Loss of "stemness" and accumulation of senescent cells is the proximate cause of decline and death"

MiFasting-Mimicking Diet Modulates Microbiota and Promotes Intestinal Regeneration to Reduce Inflammatory Bowel Disease Pathology: Cell Reportsmicking Diet Modulates Microbiota and PromoteFastinSummary

Dietary interventions are potentially effective therapies for inflammatory bowel diseases (IBDs). We tested the effect of 4-day fasting-mimicking diet (FMD) cycles on a chronic dextran sodium sulfate (DSS)-induced murine model resulting in symptoms and pathology associated with IBD. These FMD cycles reduced intestinal inflammation, increased stem cell number, stimulated protective gut microbiota, and reversed intestinal pathology caused by DSS, whereas water-only fasting increased regenerative and reduced inflammatory markers without reversing pathology. Transplants of Lactobacillusor fecal microbiota from DSS- and FMD-treated mice reversed DSS-induced colon shortening, reduced inflammation, and increased colonic stem cells. In a clinical trial, three FMD cycles reduced markers associated with systemic inflammation. The effect of FMD cycles on microbiota composition, immune cell profile, intestinal stem cell levels and the reversal of pathology associated with IBD in mice, and the anti-inflammatory effects demonstrated in a clinical trial show promise for FMD cycles to ameliorate IBD-associated inflammation in humans."

https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30181-0

LDL Cholesterol is not the correct target for treating heart disease?

This is heresy in medicine but the evidence appears sound to me.

A single exception questions a rule.  Multiple exceptions disprove the validity of a rule. The evidence is cited here based on that rule of logic.

My take away is that LDL is not the cause or appropriate  target for treatment or prediction of heart disease.

Endothelial dysfunction treatment or increased resilience is the appropriate treatment target.

Endothelial function is measured by plethysmography or increased compliance (from NO and H2S) flow mediated dilation and increased HRV heart rate variability.  Erectile dysfunction indicates decreased flow mediated dilation of the cavernosa.  ED is a predictor of premature cardiovascular events. Similarly migraine is decreased flow mediated dilation or decreased autoregulatoon of cerebral blood flow as a function of dysautonomia.

HRV is lowered by dysautonomia and increased by hormesis induced by both high intensity interval exercise (Tabata) and high intensity interval rest (Biofeedback breathing two minutes twice daily.)

Highly sensitive balanced autonomic tone or high HRV index indicates atherosclerosis resilience.

What are your thoughts on this matter?

blob:https://www.tandfonline.com/862f1599-be5e-4b7d-bb4a-006242be5749

How are Love AND Learning Related?

Resilience determines locus of control, success and happiness.

Consider that learning and loving are predominantly physiological and natural pursuits.  How well one learns and loves is therefore increased or decreased by the drivers of executive control/working memory, language, theory of mind, inference and mental time travel.  Consider first a romantic "spark" or scene from Pride and Prejudice, starting Keira Kneightly.

The camera highlights a discreet touch between Darcy and Elizabeth, flashes their facial awareness or fighting awareness and then shows Darcy clench his fist.  Body language 101 reads his taciturn face and clenched fist as struggle.  This touch or caress to fist as Darcy gives a hand to Lizzie as he helped her into the carriage after her visit is a "spark."

Aren't students a continuum of active learners and reluctant taciturn learners?

Why?

Consider a student as needing to find the "spark" and love of lifetime learning required for happiness and success.  How can we best fan this physiological spark into a flame?

We all know students who love learning or have a passion for learning. 

I posit that every one of them has resilience.

I posit that society believes that wealth and social capital is the source of resilience.

I also posit that they are wrong!

The driver of resilience is the locus ceruleus and is a function of strong sympathetic and vagal tone.  

It is physiological not sociological.  

It is plastic, malleable and can be strengthened.

Can one tune attraction and attachment in love and learning?

I posit one strengthens physiological resilience with physiological tools based on excitement/exercise AND relaxation breathing.

These can be paced just as concretely as a pacemaker produces a steady heart rate.

Jolt of noradrenaline, increases focus with awareness of effort, joined by  jolt of acetylcholine, effort floats away with the strong impression of feeling safe and content within the bubble of communion/classroom.

No longer biased, no longer judging and aware of too much or too little. All that remains is just right.

Righteousness with self, other and the world.

The perfect physiological state for learning and love of self and others.

Isn't this recapitulated in every intimate encounter physiologically with vagal arousal and sympathetic climax between attached couples. The strength of the attachment is a function of strong vagal and sympathetic tone.  Resilient individuals and teams have strong accelerators and brakes, high HRV.  (The marriage study showing success was greater with physiology than communication/teaching) I am paralleling learning with love because orthodoxy states that love is predominantly physiological and learning is predominantly pedagogical.

I have previously reframed RESILIENCE as the relative strength of sympathetic and vagal capacity in the locus ceruleus and its projections into both brain and body.  One can stratify students and their educational attainment on the resilience to vulnerable continuum.  One can also stratify their relative vulnerability to "mind altering" substance and behavioral addictions.  A secondary benefit of resilience.

Does the resilient vulnerable continuum vary with HRV?

Does educational attainment vary directly with HRV.

The resilient are vibrant learners and high on life.

The vulnerable are searching for external drivers of vitality and are willing to JOLT their bodies with stimulants and depressants.

Unfortunately, external drivers are uncontrolled and use up precious physiologic capital needed to strengthen resilience by strengthening rest AND stress.  The vulnerable who raise HRV or strengthen autonomic tone build the physiologic capital to feel confident, try and succeed. (Amy Cuddy Body Language study showing two minutes of posing/breathing reduced or increased cortisol, affected confidence, trying, and succeeding.)

Twelve step programs have no scientific validity and a poor track record for resilience building.

Does public education have scientific validity?

What track record for building resilience do average schools have?

Even if it correlates with socioeconomic status of students, aren't there exceptions?

A single exception should make one question the correlation and not mistake socioeconomic drivers as the cause.  One can certainly point to myriad examples of failure to launch from success predicted launch pads.  And vice versa.

I suspect tuning our ANS physiology will have effects on both fluid and crystallized intelligence, educational attainment, life success and happiness.

Biological Anti-Aging Biomarkers

Inflamaging and inflammation biomarkers are predictive of performance and cognition in elders.

Telomere length is a derivative of low inflammation; not vice versa.

If renal function improves, biologic age goes down and function goes up.

If inflammatory markers go down, biologic age goes down and function goes up.

If cortisol, insulin and IGf goes down, and FOXO3 and bdnf goes up, biologic age goes down and function goes up.

Conjecture from senescence markers: when senescent cells go down, and stem cell markers go up, biologic age goes exponentially down and enduring function goes up.

Why?

The fate of stem cell health determines destiny and fate.  Our bodies have two progenies; offspring and replacement somatic cells.  Therefore biologically young offspring (children, grandchildren and great grandchildren) and biologically young somatic cells PROFIT US MUCH.

https://www.ncbi.nlm.nih.gov/pubmed/26629551

Inflammation, But Not Telomere Length, Predicts Successful Ageing at Extreme Old Age: A Longitudinal Study of Semi-supercentenarians.

2015 Jul 29;2(10):1549-58. doi: 10.1016/j.ebiom.2015.07.029. eCollection 2015 Oct.

Abstract

To determine the most important drivers of successful ageing at extreme old age, we combined community-based prospective cohorts: Tokyo Oldest Old Survey on Total Health (TOOTH), Tokyo Centenarians Study (TCS) and Japanese Semi-Supercentenarians Study (JSS) comprising 1554 individuals including 684 centenarians and (semi-)supercentenarians, 167 pairs of centenarian offspring and spouses, and 536 community-living very old (85 to 99 years). We combined z scores from multiple biomarkers to describe haematopoiesis, inflammation, lipid and glucose metabolism, liver function, renal function, and cellular senescence domains. In Cox proportional hazard models, inflammation predicted all-cause mortality with hazard ratios (95% CI) 1.89 (1.21 to 2.95) and 1.36 (1.05 to 1.78) in the very old and (semi-)supercentenarians, respectively. In linear forward stepwise models, inflammation predicted capability (10.8% variance explained) and cognition (8(.)6% variance explained) in (semi-)supercentenarians better than chronologic age or gender. The inflammation score was also lower in centenarian offspring compared to age-matched controls with Δ (95% CI) = - 0.795 (- 1.436 to - 0.154). Centenarians and their offspring were able to maintain long telomeres, but telomere length was not a predictor of successful ageing in centenarians and semi-supercentenarians. We conclude that inflammation is an important malleable driver of ageing up to extreme old age in humans.

KEYWORDS: 

ALT, alanine aminotransferase or alanine transaminase; ANOVA, analysis of variance; AST, aspartate aminotransferase or aspartate transaminase; Ageing; CD, cluster of differentiation; CMV, cytomegalovirus; CRP, C-reactive protein; CVD, cardiovascular disease; Centenarian; ELISA, enzyme-linked immunosorbent assay; GGTP, gamma-glutamyl-transpeptidase; IL-6, interleukin 6; IQR, inter-quartile range; Inflammation; JSS, Japanese Semi-Supercentenarians Study; LTL, leukocyte telomere length; MMSE, Mini-Mental State Examination; NK cells, natural killer cells; PCR, polymerase chain reaction; SD, standard deviation; TCS, Tokyo Centenarians Study; TNF-alpha, tumour necrosis factor-alpha (TNF-alpha); TOOTH, Tokyo Oldest Old Survey on Total Health; Telomere; eGFR, estimated glomerular filtration rate

Publication type, MeSH terms, Substance, Grant support

Joseph Thomas (Tony) Liverma

8 Minutes of No Cost Activities Daily Will Change Your Life and Health

Biofeedback vagal nerve stimulating breathing reduced HOSTILITY and reduced hospitalizations by 50% and ER visits by 65%.

Two minutes of slow 0.1cps breathing twice daily improves costs, mood and outcome in CAD patients.  Actually this is useful for everyone with metabolic syndrome, provides a free smoking cessation benefit from acetylcholine blocking of the alpha 7 Nicotinic acetylcholine receptor, the same receptor that chantix occupies.  

This is a free treatment with infinite return on investment.  

Combined with Tabata four minutes of daily high intensity interval exercise it promotes healthy functional ANS autonomic tone in 8 minutes daily.  Autonomic dysfunction, either too much sympathetic or too much vagal tone results in damaging dysautonomia.

This is practical low hanging fruit to improve our outcomes.  Vagal tone activates the cholinergic anti inflammatory pathway and likely protects all organs and not just the heart.

Exercise and mindfulness, improved autonomic tone and function, improves anxiety and depression by 42% or results in RESILIENCE.

Shouldn't this be part of CCM? Shouldn't this be part of wellness for the 62% of our insulin resistance patients at increased risk for cardiovascular morbidity?

Couldn't this reduce health insurance costs for state teachers and employees?. Small no cost change in big populations produces large benefits and savings which compound year over year.

https://link.springer.com/article/10.1007/s12529-017-9707-7

One-Year Cardiovascular Prognosis of the Randomized, Controlled, Short-Term Heart Rate Variability Biofeedback Among Patients with Coronary Artery Disease

02 January 2018

Abstract

Purpose

Heart rate variability biofeedback (HRV-BF) is an effective psychophysiological intervention, with short-term effects of increased autonomic nervous system homeostasis, strengthened baroreflex sensitivity, and decreased hostility in patients with coronary artery disease (CAD). The study examined the 1-year HRV-BF effect on cardiovascular prognosis of these patients.

Methods

Of 222 patients with CAD referred by cardiologists, 210 were screened and randomly assigned to the HRV-BF and control groups. All patients received psychophysiological assessment and completed psychological questionnaires at pre- and post-interventions and 1-year follow-up. The cardiovascular prognosis primary endpoints included hospital readmission, emergency revisits, and mortality.

Results

The HRV-BF group had fewer all-cause readmissions (12.00 vs. 25.42%) and all-cause emergency visits (13.33 vs. 35.59%) than the control group. The low-frequency HRV in the HRV-BF group increased at post-intervention and 1-year follow-up compared with that at pre-intervention. Although no significant interaction effect was found in the standard deviation of the normal-to-normal intervals (F = 2.96, p = 0.055), it increased by 26.68% from pre- to post-intervention and 15.77% from pre-intervention to follow-up in the HRV-BF group. However, it decreased by 3.60% from pre- to post-intervention and increased by 1.99% from pre-intervention to follow-up in the control group. Depression and hostility scores decreased significantly at post-intervention and 1-year follow-up only in the HRV-BF group.

Conclusions

The long-term HRV-BF effect was confirmed by improved cardiovascular prognosis, increased cardiac autonomic homeostasis and baroreflex sensitivity, and decreased depression and hostility. HRV-BF is an effective psychophysiological intervention with short- and long-term effects in cardiac rehabilitation programs.

Joseph Thomas (Tony) Liverman, Jr.

Anti-aging or Optimum Metabolic Health in 3 Steps

Why age related decline in...

Melatonin is one axis leading to aging.

NAD age related decline in NAD is a second axis leading to aging.

Loss of protein quality control or proteostasis is a third axis of aging.

Therefore, the 1,2,3 of anti aging is the following:

Melatonin.

NR niccotinamide riboside.

Spermidine, wheat germ.

Death and frailty result from stem cell exhaustion.  This regimen is central to both somatic and stem cells survival and quality control.

https://www.sciencedirect.com/science/article/pii/S1043276018302261

Sirtuins in Metabolic and Epigenetic Regulation of Stem Cells

Highlights

As cellular metabolic and stress sensors, sirtuin family of NAD⁺-dependent deacylases are pivotal regulators of stem cell biology in addition to their well-known roles in metabolic diseases and aging.

Despite their common dependence on cellular NAD⁺, different sirtuins display cell type-specific and/or stage-dependent impacts on stem cell biology in response to various environmental cues.

Nuclear and cytosolic sirtuins modulate pluripotent stem cells and embryogenesis through regulation of pluripotency factors, metabolism, epigenetics, redox homeostasis, and cellular stress response.

Sirtuins maintain self-renewal, quiescence, and regenerative capacity of adult stem cells and protect against adult stem cell depletion in response to stress and aging.

Sirtuins are highly conserved NAD⁺-dependent enzymes that are capable of removing a wide range of lipid lysine acyl-groups from protein substrates in a NAD⁺-dependent manner. These NAD⁺-dependent activities enable sirtuins to monitor cellular energy status and modulate gene transcription, genome stability, and energy metabolism in response to environmental signals. Consequently, sirtuins are important for cell survival, stress resistance, proliferation, and differentiation. In recent years, sirtuins are increasingly recognized as crucial regulators of stem cell biology in addition to their well-known roles in metabolism and aging. This review article highlights our current knowledge on sirtuins in stem cells, including their functions in pluripotent stem cells, embryogenesis, and development as well as their roles in adult stem cell maintenance, regeneration, and aging.