I often stick to long-form, theme-centered articles, but usually, I often read many single articles worth covering even briefly, but I postpone for so long, I end up never writing about them. To this matter, this will be a mixed bag, if they fit a theme, it was merely by happy accident.
For various correlated and non-correlated reasons many people develop or effectively are B12-B9 (Folic Acid) deficiency, and both deeply impact your body and immune system, but especially important, mitochondria and the brain. By just supplementing B12-Folic acid, the brain can recover from degrees of neurological dysfunction.
Some Long Covid/ME-CFS people develop or suffer from undiagnosed B12/9 deficiencies, it is cheap to test, and cheap to treat, older people, and a decent portion of persons with chronic infections usually either have a diagnosable or subclinical (meaning tests will miss it) deficiency of both.
Depending on genetic variability, previous medical history, and other variables some people may only correct their deficiency with B12 injections, no matter how much “pills” they pop in, the body and cells just don’t absorb, something else to have in mind if you tried to supplement for months and your levels barely moved a inch.
The second is also positive and builds upon a couple of topics I covered this year in this publication, fasting, and the ketogenic diet. To clarify, caloric restriction, also referred to as food deprivation is reducing the daily caloric intake but still maintaining proper nutrition, unlike fasting which is not eating at all.
Here the authors uncovered the distinct potent anti-inflammatory effects of “hunger”, so let me explain how because it is rather complex.
AgRP is neurons found in the hypothalamus that control food intake (hunger) and energy balance, the periventricular nucleus is part of the hypothalamus. So these neurons which are not numerous exert an anti-inflammatory effect on peripheral tissues (let’s say, the joints of your feet and hands) by sending the signal through the PVN traveling through the vagus nerve, and reaching the peripheral regions.
A few neurons in a part of your brain can effectively lower the inflammation in your joints, which is very distinct from, for example, the ketogenic diet or fasting. Something to bear in mind (I am often surprised how very small pieces of information often help random people who randomly find my Substack, so this is why I am sharing).
Exercise Regulates Myokines on Aging-related Diseases through Muscle-brain Crosstalk
Myokines are the cytokines created by muscle fibers, receptors for them are found in muscle (duh), fat, liver, pancreas, bone, heart, and immune. Basically, they can exert effects on your most important organs. In response to exercise, they affect mood, sleep, neuroplasticity, and a lot more.
The paper above goes to great lengths to discuss literature and the many studies finding on exercise impact on the body, including the recovery process, but one section, in particular, is the most significant for older people.
The main myokines associated with muscle-brain diseases are BDNF, IGF-1, Irisin, CATB, IL-6, FGF21, and VEGF. AD is the most common age-dependent neurodegenerative disease, characterized by the formation of senile plaques from β-amyloid (Aβ) deposits and neurofibrillary tangles from the accumulation of hyperphosphorylated tau proteins. Aβ is produced by amyloid protein precursor (APP) under the cleavage of β-site APP-cleaving enzyme 1 (BACE1) and γ-secretase. In contrast, α-secretase competitively inhibits βsecretase activity and reduces Aβ production. It has been found that BDNF, IGF-1, and CATB are all effective in inhibiting Aβ production and accumulation. BDNF both enhances α-secretase activity and produces soluble amyloid precursor protein α (sAPPα) with neuroprotective properties and attenuates Aβ42-induced neuronal toxicity, mediating motor inhibition of BACE1 content and activity [54]. IGF-1, a key regulator of CNS neuronal function, enhances synaptic plasticity, increases synaptic density, inhibits Aβ production, and reduces neurofibrillary tangle formation and cerebral amyloidosis. The upstream agonist of the irisin precursor FNDC5, peroxisome proliferatoractivated receptor gamma coactivator-1α (peroxisome proliferator-activated receptor γ coactivator-1α, PGC-1α), is rapidly activated under exercise stress conditions and inhibits Aβ production and accumulation by downregulating BACE1 levels [55, 56]. CATB accelerates Aβ metabolism via the lysosomal pathway [29]. In addition, IL-6 reduces oxidative stress in the body by exerting its anti-inflammatory effect, and VEGF inhibits Aβ-induced endothelial cell apoptosis [57, 58]. Sarcopenia is an age-related degenerative disorder with progressive loss of skeletal muscle mass and reduced muscle strength. There are four broadly accepted causes of sarcopenia, including aging-induced oxidative stress and mitochondrial dysfunction, activation of apoptotic signaling pathways in skeletal muscle cells, impaired autophagic flow due to low levels of cellular autophagy, and increased inflammatory cytokines [59-62]. Exercise can improve muscle mass and function by promoting protein synthesis, decreasing inflammatory factors, inhibiting the expression of apoptotic factors in senescent muscle atrophy, increasing cellular mitochondrial mass, and enhancing metabolic enzyme activity [63-65].
In simplified terms, BDNF enhances α-secretase activity and produces soluble amyloid precursor protein α (sAPPα) with neuroprotective properties. IGF-1 enhances synaptic plasticity, increases synaptic density, and inhibits Aβ production. CATB accelerates Aβ metabolism via the lysosomal pathway.
Irisin inhibits Aβ production and accumulation by downregulating BACE1 levels. IL-6 reduces oxidative stress in the body by exerting its anti-inflammatory effect, and VEGF inhibits Aβ-induced endothelial cell apoptosis.
Sarcopenia, an age-related degenerative disorder with progressive loss of skeletal muscle mass and reduced muscle strength, can be improved by exercise. Exercise promotes protein synthesis, decreases inflammatory factors, inhibits the expression of apoptotic factors in senescent muscle atrophy, increases cellular mitochondrial mass, and enhances metabolic enzyme activity. Another reason for you to just go exercise.
And the following is something I mentioned last time. Omicron and “brain stuff”. Before discussing both papers, a foreword.
This shouldn’t make you worry, if you take just the minimal amount of care necessary and are healthy, 99% chance it will never occur with you. Daily Magnesium, Selenium, Vitamin C, any antioxidant of your choice (NAC+Glycine, Quercetin, etc), and either low-dosage of daily Vitamin D+K2, or occasional high dosages of Vitamin D, and you are set. Limit any respiratory infection inflammation and you are set.
When Omicron surfaced, after a few months of paying close attention to large amounts of clinical data, I voiced my concern about the change of tropism (tropism means the places something goes to) and the apparent preference of Omicron going towards the brain.
In this cohort (group) per the paper twenty-nine participants received 1 or 2 doses of the vaccine, 17 received 3 doses, and 15 did not report their vaccination status. This study was done in China, they do not use mRNA, and arguably the Chinese vaccine is the least toxic of all vaccines (it still can do damage, but it is a lot less well-defined than mRNA, but it is orders of magnitude less in my opinion at this point).
The patients here had an acute but short course of infection, and this is one of the few studies with MRI tests done before and after infection. The changes and damage in the brain were then correlated with questionnaires, thus providing a new base for the emotional and cognitive effects of Omicron. These changes can help understand how Omicron subvariants affect the nervous system and brain, and help the process of developing early detection so physicians can avoid the neurological sequelae.
Similar to the above, acute infections but in this particular case in children, and half of the survivors had neurological sequelae after. One aspect that surprised me was the seven children that died, with the average time being 35 hours, which is incredibly fast. Cytokine storm, septic shock fast.
What is the point of sharing both of these Omicron papers ? It is not for confirmation bias, but rather to demonstrate this isn’t just a cold, many parts of Omicron were in the original Wuhan, which can impact the body and immune system significantly. I don’t “data mine” social media anymore (no point really, data is poisoned to hell and back) but many people contact me to ask for advice, suggestions, or help and most of them are unvaccinated or ask help for someone who is too.
The vast majority only had 2 Omicron infections since 2020, and they do develop some long-term sequelae, even when they only experience moderate infection. Avoid being infected, or minimize the infection and you are good. Just don’t drop your guard down yet, I know I won’t, and for the record, I don’t get infected anymore by any SARS-CoV-2 lineage, and still, I am careful.
In simple terms, Omicron is much milder than Wuhan to Delta variants but has an absurdly more complex individual variability and severity, which makes everything more complicated. Exercise, a good diet, some supplements and you avoid most of this.
I will some significant information on Mycoplasma-Omicron in the commentary section. Now, back to writing about how the body cleans Misfolded Proteins. Until then.
If you choose to support my work, thank you very much. And a year’s end/2024-2025 message. The spirit for my birthday.
Given how many events, papers, everything else going on, I didn't have the time to write about recent Omicron immune responses measurements, but I spent a few hours today reading recent papers by Chinese groups, and was surprised to find that both in vaccinated and unvaccinated, Omicron elicits a strong IL-17 response (the authors will argue this is positive, but I digress).
Higher levels of IL-17, IL-10, TNF-a are all contributors to developing Mycoplasma Pneumonia. Too much of anything is bad, add the feedback loop of Omicron > Influenza > bacterial infection and you get the recent trend.
I wish everyone a good week. In case you are curious, I will be 38 in December 9.
Professor - Do you remember when you'd hear stories about how when so & so was young, they suffered a really bad cold - flu - infection and that's how they wound up in their current "condition"? Perhaps your too young to remember those days. One must remember, HIV predates the Gunfight at The OK Corral. But I digress, I remember when getting up (in the morning or from any position) did not involve sound effects. Good times. But I date myself. Happy Birthday Kid! Enjoy the gift Mr. Mulder. https://youtu.be/z92bykaeV4o?