Mitochondria, movement, the cerebellum and dystonia.

Movement may be the signal our symbionts need in order to continue functioning as symbionts instead of taking over as pathogens.

Any type of sudden shock to the system causes an abrupt drop in mitochondrial production of ATP.

*I added an addition of some value near the top of this post: Geert Vanden Bossche is trying to tell us something about jab effects on immunity of the jabbed / maybe T-cell support would help. (substack.com)

Another slide from: Pick Your PICS: Mitochondrial Changes, Inflammation and Nutritional Interventions, Nestle Medical Hub for Healthcare Professionals. Presented by Keith Miller, MD, FACS; Martin Rosenthal, MD, FACS; Beth Taylor, DCN, RD-AP, CNSC, FAND, FASPEN, FCCM.

Slide from: Pick Your PICS: Mitochondrial Changes, Inflammation and Nutritional Interventions, Nestle Medical Hub for Healthcare Professionals. Presented by Keith Miller, MD, FACS; Martin Rosenthal, MD, FACS; Beth Taylor, DCN, RD-AP, CNSC, FAND, FASPEN, FCCM.

The ICU team can help get people through the immediate shock effects, if help arrives quickly enough, however, will the person then be one of the rapid recovery patients or one of the ones that develop long term symptoms of PICS?

Any level of movement can help mitochondrial function in older adults (citation/quote in some post).

Mitochondria and exercise:

More intensive physical training leads to more mitochondria biogenesis. Activity in general seems to help promote better mitochondrial function in several ways. CamK, p38MAPK, and AMPK are promoted which leads to PGC-1a. The AMPK and PGC-1a and p53 which is also promoted by physical activity, all lead to improved mitochondrial function by promoting biogenesis, ATP production, and mitophagy, removal of dysfunctional mitochondria. (Sorriento, Di Vaia, Iaccarino, 2021, Figure 2)

An increased level of PGC-1a is associated with more functional mitochondria and increased endurance for physical activity. (“Use it or lose it”, does seem to be true.)

“The muscle-specific gene Zmynd17 is known to control mitochondrial quality in muscle, especially in fast glycolytic muscles. Its deletion leads to abnormal mitochondria accumulation, whose number is significantly reduced after 10 weeks of voluntary exercise (Fujita et al., 2018). These findings underline that exercise’s beneficial effect occurs independently from Zmynd17 activity, suggesting the specificity of [physical activity] PA effects (Yoshioka et al., 2019). It has been shown that acute exercise increases mitofusins’ expression in human skeletal muscle and stimulates mitochondrial fusion by activating the PGC−1α/ERRα pathway (Cartoni et al., 2005). PGC1a overexpression in muscle leads to dense mitochondria with typical cristae structure and increases the endurance exercise capacity (Casuso and Huertas, 2020)” (CC-BY the authors: Sorriento, Di Vaia, Iaccarino, 2021)

It may be very important to help bedbound people to move and to encourage more mobile people to increase their activity, and full range body movement.

If inflammation is early stages of decomposition and signaling is promoting it, then different signaling is needed as a solution. This likely involves microRNA and polyphenols may promote some of the improved signaling that is needed, in addition to activity having that effect.

“MicroRNAs are mainly located in cytosol or nucleus. Recent studies suggested that microRNAs contain sequence elements that affect their subcellular localization [10]. Moreover, Ago2 has been implicated as a carrier to transport microRNAs between mitochondria and cytosol [11]. A number of studies have shown that microRNAs can translocate into the mitochondria at either pre-RISC or mature-RISC conformation [12], indicating a special impact of these microRNAs on mitochondrial function. For example, miR-1 stimulated mitochondrial genome-encoded transcripts by Ago2-mediated translocation into the mitochondria during muscle differentiation [13]. Similarly, miR-181c and miR-378 regulated mitochondria targets in cardiomyocytes, leading to alteration in electron transport chain, fatty acid metabolism, and apoptosis under metabolic stress [14–16]. A new term “MitomiR” was created for the microRNAs localized in mitochondria to regulate gene functions [11, 17]. These microRNAs regulate specific pathways contributing to energy metabolism at the mitochondrial level [18, 19].” (Wang, X., et al., 2017)

A medical approach might be to try to provide a specific microRNA - hesperidin alone affected more than 100 microRNA - in beneficial ways. Wouldn’t it make more sense just to give people hesperidin? or citrus peel (unless histamine sensitive)?

The problem is the for-profit model and the authoritarian view of “controlling” health. Newsflash: health is not something a doctor can sell you - it is something your body has to build and maintain daily. We need to focus on sending “build and maintain” signals and activity can send those. Over-exertion can lead to too many additional inflammatory signals though, so a moderate pace for increasing strength and endurance is needed. Nrf2 promoting phytonutrients and foods also send build and maintain signals.

In trying to power write a 12,000-page paper in a couple months, I ended up with 70,000 words and a lot of pent-up energy - too much sitting. Also, eyestrain, (whining over now). It was a reminder that physical fitness goes fast. My endurance level is not great.

One of the mitochondria webinars briefly discussed burnout and quoted a worker from CoV outbreak era saying they were moving so fast it felt like revolving doors in their mind. That stood out to me as my own chores as a caregiver for two needy patients and a house and yard (and writing projects) had left me so busy at times that I commented to an aide that my head felt like it couldn’t keep up. The constant doing the next task, and the next, and the next, and the next, literally left my body and brain feeling slightly ahead of itself, or slightly behind. A brief pitstop to let the swirling energy slow-down was needed.

Dystonia is a topic I described in my Genes Table series. It is a movement disorder with a range of symptoms/conditions that vary in severity. I have had a mild “writer’s cramp” version all of my life. I thought it was just normal and everybody’s hand fell asleep if they wrote too long or colored.

Specific example of writer’s cramp - copying this three times left me shaking out my cramping and slightly numb hand.

Merry snow to you, everyone!

The dystonia of Writer’s Cramp is not just about writing though. If I sit too long, my whole body/legs go numb and I limp a little and have to shake out my legs kind of when I do stand up. Sitting style meditation does not work well for me because my body gets pins and needles of pain and goes numb. Walking meditation or calmly doing the dishes is better meditative time for me. “Fidgeting” as an ADHD person may be a need to keep the body in motion for the nerves to keep firing instead of going numb. An external source of cannabinoids makes this problem less of a constant loss of sensation and coordination for me. Dance is my way of keeping my body from cramping up in range of motion shortening permanent cramps. My left shoulder and side are tighter and want to turn that direction as if I had torticullis during fetal development.

• Torticullis - baby’s neck stays permanently turned toward one direction (when at rest, can move the neck, doesn’t want to, the comfort position is turned towards the preferred side, and stay there), so the muscles are shortened and tightened on that side and the baby isn’t able to fully turn their head the other direction. It can be caused by always feeding a baby in the same position or propping with a bottle in the same position.

I added a little more to the Neural Tube Defects section that is related to scoliosis and that info is likely related to the ‘torticullis’ effects that I have noticed about myself: Phenotype - ADHD and autism comorbidly? / Gene Table & video by Yo Samdy Sam. (substack.com)

Proprioception - sensing body movement - may be affected by gene differences and chronically not quite right muscle signaling may pull the skeletal frame out of alignment. Putting the child in a movement limiting brace would probably not help the child as much as the posture exercise that my pediatrician had instructed me on when I was a child. One visit was all it took, and he may have asked at later appointments if I was doing the exercise, but I don’t remember that as well. I did do the posture exercises and later took ballet to try to improve my clumsiness. I learned how to fall more gracefully. When my ADHD kicks in, my body gets physically clutzy. I run into doorways with my left shoulder. My left side proprioception is a weak point for me, to use the fancy term.

“Suck in your gut, pull in your butt, and stand up straight and tall” - repeat ten times, several times a day. - Family doctor/pediatrician, circa ~ 1974.

The exercise rhyme was simple enough to remember, and a little funny, and the repetition led to the unconscious switch to better posture all the time. Genius.

Turns out “LongCovid” was also simply “Long Illness” in people with other respiratory infections. RT? ME/CFS? More simply: Anemia of chronic inflammation?

“Long Illness” following a viral infection may be Retinoid Toxicity or anemia of chronic inflammation. A study that followed CoV positive and negative people found more prevalence of Long Illness in the people who hadn’t tested positive for CoV. They may have had some other respiratory virus. Rather than taking that as LongCovid isn’t real, we need to see it as post illness recovery can be a problem for some people, no matter what the virus was.

Long covid versus long illness: when other viruses cause long term symptoms.

Actin, glyphosate, and microtubules are likely involved in whether Rapid Recovery or Long Illness (nice term), occurs post ICU or other “shock” of an immune challenge to the body.

Microtubules are part of the difference between healthy cells and cells that are targeted by the anti-parasitic medication fenbendazole. Case Report: Metastatic Breast Cancer, age 83, F...Fenbendazole Can Cure Cancer (substack.com)

Case Report: Metastatic Breast Cancer, age 83, F...Fenbendazole Can Cure Cancer

*Preliminary notes - I’m going to leave this for now:

Physical activity promotes mitochondrial health.

“Interestingly, physical activity stimulates mitochondrial function by promoting mitochondrial biogenesis (Montero & Lundby, 2017), but also by actively inducing the degradation of …” (Houzelle, et al., 2020)

MicroRNA with a nuclear origin are involved in regulation of mitochondrial activity.

“Recent studies suggest that nuclear-encoded microRNAs (miRNA) are able to translocate into the mitochondrial compartment, and modulate mitochondrial activities, including [Ca2+]m uptake. Apart from this subset of miRNAs, there…” (Jaquenod De Giusti, Roman, Das, 2018)

MicroRNA help regulate p53.

“In searching for the downstream targets, p53 was identified as the direct target of miR-30 family members. Mitochondrial fission requires the activity of a dynamin-related protein-1 (DRP1) …” (Li, Jiao, Gao, Prabhakar, 2012)

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

Reference List

(Houzelle, et al., 2020) Houzelle, A., Dahlmans, D., Nascimento, E.B.M., Schaart, G., Jörgensen, J.A., Moonen-Kornips, E., et al., (2020). MicroRNA-204-5p modulates mitochondrial biogenesis in C2C12 myotubes and associates with oxidative capacity in humans. J Cell Physiol. Dec;235(12):9851-9863. doi: 10.1002/jcp.29797. Epub 2020 May 26. PMID: 32452584; PMCID: PMC7586823. https://onlinelibrary.wiley.com/doi/10.1002/jcp.29797

(Jaquenod De Giusti, Roman, Das, 2018) Jaquenod De Giusti, C., Roman, B., Das, S., (2018). The Influence of MicroRNAs on Mitochondrial Calcium. Front Physiol. Sep 21;9:1291. doi: 10.3389/fphys.2018.01291. PMID: 30298016; PMCID: PMC6160583. https://www.frontiersin.org/articles/10.3389/fphys.2018.01291

(Li, Jiao, Gao, Prabhakar, 2012) Li, P., Jiao, J., Gao, G., Prabhakar, B.S., (2012). Control of mitochondrial activity by miRNAs. J Cell Biochem. Apr;113(4):1104-10. doi: 10.1002/jcb.24004. PMID: 22135235; PMCID: PMC3325319. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325319

(Sorriento, Di Vaia, Iaccarino, 2021) Sorriento, D., Di Vaia, E., Iaccarino, G., (2021). Physical Exercise: A Novel Tool to Protect Mitochondrial Health. Front Physiol. 2021 Apr 27;12:660068. doi: 10.3389/fphys.2021.660068. PMID: 33986694; PMCID: PMC8110831. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110831/, “Exercise activates several intracellular pathways to regulate mitochondrial function.” Figure 2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110831/figure/F2/ (Accessed: 12 Dec 2022)

(Wang, X., et al., 2017) Wang, X., Song, C., Zhou, X., Han, X., Li, J., Wang, Z., et al., (2017). "Mitochondria Associated MicroRNA Expression Profiling of Heart Failure", BioMed Research International, vol. 2017, Article ID 4042509, 10 pages, https://doi.org/10.1155/2017/4042509 Available at: https://www.hindawi.com/journals/bmri/2017/4042509/ (Accessed: 12 Dec 2022)

(Houzelle, et al., 2020) Houzelle, A., Dahlmans, D., Nascimento, E.B.M., Schaart, G., Jörgensen, J.A., Moonen-Kornips, E., et al., (2020). MicroRNA-204-5p modulates mitochondrial biogenesis in C2C12 myotubes and associates with oxidative capacity in humans. J Cell Physiol. Dec;235(12):9851-9863. doi: 10.1002/jcp.29797. Epub 2020 May 26. PMID: 32452584; PMCID: PMC7586823. https://onlinelibrary.wiley.com/doi/10.1002/jcp.29797