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Fasting -> Inhibits mTORFasting -> lipid metabolism regulationFasting -> P-Glycoprotein expression changesFasting -> Immune system shiftsFasting -> Blood Brain Barrier function + toxin clearance.Fasting -> Better Intestinal barrier functionFasting? Nah. Acute Aestivation. https://t.co/RWydlod7x9
Fasting -> inhibits mTORhttps://t.co/rosYeS1iEI
@Mangan150 @jasonmpeirce @naval Nice."Leontieva et al recently showed that a once-weekly treatment with rapamycin extends lifespan in high fat-fed mice without altering glucose or insulin levels"https://t.co/n97GkGz0QySo it's fast mimicking? https://t.co/Ze3vNPE7cuFun.
mTOR impacts lipid metabolism https://t.co/aBTZIT90Dd
Fasting does too?"However, mechanistic evidence is largely limited to findings from rodent studies, thus necessitating focused human studies, which also incorporate more dynamic assessments of glucose and lipid metabolism."https://t.co/Zf8yRusFOA
Fasting -> P-Glycoprotein expression changeshttps://t.co/gY4YFWC2HP
Fasting -> Immune system shiftshttps://t.co/iHdEybxCci
Why would a lipid membrane related chemical impact immune cells ability to get fuel?https://t.co/mFdVFvEFyh
Why would a lipid membrane related chemical impact neuroinflammation?https://t.co/4fpfsIdoGT
Fasting -> Blood Brain Barrier function + toxin clearance.https://t.co/k7Dv411ILn
Why would conditions with impaired sleep lead to increased buildup of a plaques?https://t.co/zH5a5uTqym
How does blood brain barrier work?https://t.co/20nBm2qKAt
Why would a lipid membrane related chemical impact blood brain barrier cells ability to let stuff thru?https://t.co/Let81AJ8mF
Fasting -> Better Intestinal barrier functionhttps://t.co/MwXvHcn85s
Why would a lipid membrane related chemical impact intestinal barrier in IBD?https://t.co/MMI4bXmwKu
Do you even understand?https://t.co/MwXvHcn85s
Really makes you think.https://t.co/kL0Dj95K04
Thank you @MMMalign for pointing out p-glycoprotein impacts drug metabolism and talking to me about liver enzyme's role in this space.Glycoproteins are really interesting.https://t.co/g5pAVJRrLX
Gonna bet money that TOR and mTOR's role in immune system changes is actually just a way for the body to shifting metabolic states.https://t.co/i9JASkJMsa
Dietary signaling related kinases going to respond to environmental factors. News at 11."has become clear that mTOR plays a central role in regulating the outcome of antigen recognition in sculpting the outcome of the adaptive immune response. "https://t.co/sF968aJkRe https://t.co/Ex8bYZz0Et
The anti-aging aspects of Rapamycin likely just compensating for (high-fat + high-carb) diet.Poor lipid metabolism is one of the hallmarks of diabetes and seems to be intimately tied to gut bacteria and liver function.https://t.co/aBTZIT90Dd
Some studies in rats suggest long term inhibition mTOR may drive liver problems despite showing short term gains. https://t.co/HCufOWFBjUIf we assume that the body is adapting immune function and resource demands in a complex way. How would you compensate for this?
What would an impaired liver cause? Histamine responses in the skin and increased mucus in lungs.Push this system too hard for too long without compensation (via endocannabinoid signaling's impact on liver repair?) and you get a bad time.https://t.co/mJHRufWcVF
Did you know ants don't age? It's amazing where a little cross-silo investigations into metabolic processes will get you.https://t.co/P5JRhs8xNp
"Law of the locust: a tale of swarms, cannibals, ageing and human obesity"https://t.co/2FD8B4b1Sh
Do you ever wonder if you can explore [serotonin's role in why hamsters eat each other] as a proxy method to investigate [why immune system changes in termites lead to cannibalism as a illness defense system]?Why not?https://t.co/HnWr07OumP
Hello yes. I accidentally an entire psychiatrics disorder. Send help.https://t.co/ZFrXCaXBBz
Solve autism, they said. I'm sure you won't undermine 85% of the medical system's models of disease, they said.https://t.co/AHm77s0FlH
My brain hurts rn.https://t.co/QBQnFoJ8CI https://t.co/QGWzCLeaVM
No thanks @elonmusk, I don't want a computer chip from a large corporation to be implanted in my brain. I think it's a good idea tho, and your heart is in the right place.I want to chip myself with open technology and solve my own autism. Not become a borg. https://t.co/tedu3WggzW
Here's a 2018 study in mice that shows a ketogenic diet directly impacts factors associated with BBB and Alzheimer's disease via P-Glycoprotein and mTOR, with direct impacts on beneficial gut bacteria.https://t.co/drdz9ZPthQ https://t.co/hooLTw5mac
And here's a tweet from a month before that study was published.https://t.co/Z3leKUAtHZ
After all that wine I went on a 3 day fast.Holy shit, true ketosis state is a night and day difference for my brain fog issues. I feel awake in the morning + haven't had a sensory processing trouble since Sunday.I wrote a diary on the fast on mastodon: https://t.co/9bcHvAafos
Advances in scientific understanding are always violations of the existing paradigm.Thomas Khun wrote a whole book on that topic. Its not that bad. A little dated.https://t.co/5fW7nGGurO
I will violate science if science is wrong."Science is not immune to interpersonal bullshit. Scientists can be stubborn. They can use their gravitas to steamroll new ideas. Which means those new ideas often only prevail when older scientists die."https://t.co/aD7lkqsMBq
Bears my fangs. I can wait.I got like all those longevity genes and figured out how methylation factors of gut bacteria impact telomeres.https://t.co/u9oWELVhQv https://t.co/pFj7UqhGZV
I can stay irrationally exuberant longer than academia can maintain it's grip on scientific advances.https://t.co/SXFm0fujA8
Holy shit."P-glycoprotein 1 also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1)"https://t.co/cSG4Lri1uJhttps://t.co/p1UeDjAFo0
"Butyrate protects against high-fat diet-induced atherosclerosis via up-regulating ABCA1 expression in apolipoprotein E-deficiency mice"https://t.co/DrQdpSnaIIIn my notes from 6 months ago.P-glycoprotein == ABCA1Direct ties from microbial butyrate to my gut health, lol.
"SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition"https://t.co/HuqoCxvfNoLMAOhttps://t.co/l9WQjcM4Go
I reasoned that these things must necessarily be connected.https://t.co/IKtdBi4jLw
Butyrate function impairment? In my model of aging?Gut bacteria being involved is more likely than you think.https://t.co/oJqh7ejoWt
"One interesting hypothesis generated by this study suggests aging could be more generally modulated by the gut microbiome, and more extreme imbalances of gut bacterial populations can result in earlier age-related diseases."https://t.co/ruwiJ5QIEShttps://t.co/IJlUjk6cou
Fasting -> Hair growth?(Via biotin ala gut bacteria shifts paired up with various other factors related to mTOR associated pathways? https://t.co/jyXVJQdrbG) https://t.co/vkyjzdNtTG
"at quiescent (telogen) [...] stimulated [...] by small molecules that activate autophagy, including the metabolites α-ketoglutarate (α-KG) and α-ketobutyrate (α-KB), and the prescription drugs rapamycin and metformin, which impinge on mTOR and AMPK" https://t.co/dh3saNZpIx
A scent."α-Ketobutyrate is transported into the mitochondrial matrix, [bla bla bla...] propionyl-CoA [bla bla bla...] This is first through the enzyme mitochondria propionyl-CoA carboxylase with biotin as a cofactor to produce (S)-methylmalonyl-CoA."https://t.co/4eg0mqelWE
A scent."α-Ketoglutarate is transaminated, along with glutamine, to form the excitatory neurotransmitter glutamate. Glutamate can then be decarboxylated (requiring vitamin B6) into the inhibitory neurotransmitter gamma-aminobutyric acid."https://t.co/a04pb64gRR
So what happens if your gut is overrun with B6 eating H pylori?https://t.co/0PA9usiWAcMaybe cancer?
Maybehttps://t.co/dL4c4sj3C7Maybehttps://t.co/aSi8z6HdwjWhy tho?
BECOME DOGEhttps://t.co/i40HW1yQA1Fulfil the prophecy.https://t.co/UOnYDRLWco
"During the past 30 years, an intense wave of clinical investigation has attempted to dissect the putative links between vitamin B6 and cancer."https://t.co/EKHlmNyvBDIts gut bacteria via interactions with inflammation effects driven by H Pylori's sequestering of it.Dumb.
"80%of pets have gum disease by age 3.This is a life-threatening epidemic."https://t.co/xFFmCZmWkHhttps://t.co/RtaOS7mljU
Red wine helps fight Alzheimer'sbecause red wine contains nitrites,which when combined red wine's boost to stomach acid, https://t.co/MRBfSoRYOmand resveratol https://t.co/mZ9md1ha9shelps kill H. Pylori.H. Pylori is triggering Alzheimer'shttps://t.co/GpRFeBk9TC
Vitamin B6 can't be absorbed if your gut isn't processing things properly and full of things that eat it. So of course supplementing it isn't going to help unless you condition the gut.We see Vitamin B6 in the blood as a side effect of gut health.
"Unexpectedly, inhibition of the mTOR pathway both by chronic rapamycin treatment and by genetic means decreases longevity of Terc−/− mice, in marked contrast to lifespan extension in similarly treated wild-type mice."https://t.co/Nd0cLKRg6Phttps://t.co/goFCS57EHv
"These results place mTOR in a complex immunoregulatory context by controlling innate and adaptive immune responses."https://t.co/5gI5lEgBUshttps://t.co/WT39e0VzSq
"IL-6, when endogenously released during systemic inflammation, is pyrogenic by binding to IL-6Rα on brain endothelial cells to induce prostaglandin [...] probably in concerted action with other peripherally released cytokines"https://t.co/G4EWcU6cT8https://t.co/F4agYLHqlI
Fever related viruses => mTORC1 + IL6"To further elucidate the metabolic effects of rapamycin in vivo, we examined its influence on the induction of beige adipocytes and thermogenic gene expression in white adipose tissue (WAT)."https://t.co/9Bpza98i51https://t.co/1YYUe3Ps3t
Pyrolytic autocatalyzed cascade failure.https://t.co/QoCZj5HtpC
I can predict aging and fertility now. Trivially."More important, the mTOR inhibitor preserved the animals’ fertility: treated mice gave birth to an average of seven pups, essentially the same number as those untreated." https://t.co/I03E296lXA
mTOR impacts immune function and aging-> mTOR impacts lipid signaling-> mTOR impacts cancer-> mTOR probably impacts fertilityTherfore"An Experimental Cancer Drug Could Extend Women’s Reproductive Window"https://t.co/VkSUb5kyNxI predict things.https://t.co/mNde0AGZxn
Going thru and looking at the jokes I make and mining them for insights into immune function and hibernation.https://t.co/9VEYSxS1bM
I litterally I go looking for things my predictions make. Like fertility and telomere length ought to be tied to factors around hibernation. and find that scientists are surprised by it. 😹https://t.co/uSQdyBb9qk
"Collectively, these data indicate that [Caloric Restriction]-induced metabolic improvement especially in body weight reduction is mediated by intestinal microbiota to a certain extent."https://t.co/YeSY6n8Byd
"Homogeneous intrinsic neuronal excitability induces overfitting to sensory noise: A robot model of [autism]"https://t.co/XZWwm1jUL6 🧐
"would you believe me if I told you that Dr. Eggman is actually just an AI wearing one of the many skins he has? Well.."https://t.co/Qywk6h3lAkhttps://t.co/dUZh7g1CuD https://t.co/xLfS4IBfA6
"he purpose of this review is to introduce the role of mTOR signaling pathway on apoptosis, autophagy, growth, and metabolism of tumor cells, and to introduce the research progress of mTOR inhibitors in the tumor field."https://t.co/rwCz9cvSgnhttps://t.co/ogOYYj8zJm https://t.co/VLat3yySFg
"In this Review, we summarize the experimental evidence from recent peer-reviewed studies and provide a brief overview of the causal relationship between [probiotics etc] on the components of PI3K/Akt/mTOR signaling pathways and human disease."https://t.co/WiUqnctne6
Do you ever try to predict how a metabolic pathway impacts fertility?https://t.co/tMf9DaDakZ
mTOR impacts immune function and aging-> mTOR impacts lipid signaling-> mTOR impacts cancer-> mTOR probably impacts fertilityTherfore"An Experimental Cancer Drug Could Extend Women’s Reproductive Window"https://t.co/VkSUb5kyNxI predict things.https://t.co/mNde0AGZxn
Or follow people who know a lot about metabolic function related to fasting?https://t.co/tE6qurlRpl
Or wonder why certain things seem to boost neurogenesishttps://t.co/yX3rQZE8us
It's amazing how far reaching mTOR and related pathways are when it comes to things like smell.https://t.co/rMdnb2NdhH
"Previous studies have suggested that the serine/threonine kinase mTOR — a known mediator of growth and proliferation, particularly as part of the mTOR complex 1 (mTORC1) — may be important in intestinal tumorigenesis."https://t.co/jBkqauuhID*sniffs*https://t.co/bl98Lo9YeO
B6 in bananashttps://t.co/zJcz9zNDmZ
"Unlike other forms, the serotonin found in bananas doesn’t cross the blood-brain barrier, which means it can’t get into the brain to supplement the serotonin that's naturally produced by the body"https://t.co/D8B5WPy1V5So what about gut-brain-axis tho?https://t.co/dMy0P06nws
B6 in garlic.https://t.co/mI7qXyclep
"The Guide" story arc is fun here. It showcases how one's ego and knowledge can hide the truth. Tenzin has been researching this stuff all his life, but it was his child who actually managed to act as a guide.Should have ate some onion banana juice TBH.https://t.co/hrT8pI22VU https://t.co/q1S1YGf4zy
"Serine and one-carbon metabolism, a bridge that links mTOR signaling and DNA methylation in cancer"https://t.co/J2Gndac8tRhttps://t.co/sQyTA0CV6r https://t.co/Z8ylNypwxx
M(o)th(er) F(ucke)Rhttps://t.co/YEA2IQcl9F
So many complex methylation pathways, so little time.https://t.co/lDJjEUrpcv
"Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency."https://t.co/jzAyIrGyP0"it bricks the receptor with the inactive pyridoxine blocking active form pyridoxal-5′-phosphate" https://t.co/gLenkm41kc
So if I can optimize the active form production it should be fine it seems?hmmm... I wonder what impacts that."Pyridoxal 5′-Phosphate-Dependent Enzymes at the Crossroads of Host–Microbe Tryptophan Metabolism"https://t.co/5p6Fu8eieR
"PLP-dependent enzymes [...] are estimated to be involved in ∼4% of all catalytic reactions, making this an important class of enzymes. Here, we [...] characterize three novel PLP-dependent enzymes from bacteria in the human microbiome" https://t.co/nDt2E6CljJ
"Cecal propionate and butyrate were significantly reduced in [low b6] rats irrespective of sex. Host vitamin B6 deficiency but not excess significantly alters gut microbial composition and its metabolites."https://t.co/SurUn1pKf5
Just found this recent review on vitamins and gut. Covers Crohn's Disease among others:"Vitamins, the gut microbiome and gastrointestinal health in humans" [NOV 2021]https://t.co/73XlF59KqUAs always, Grimhood be dropping that knowledge ahead of time. https://t.co/uhx7gne7k6 https://t.co/xmhZVlhRSF
*digs out my b2 vitamin that I was using as a tracer*https://t.co/98JHIJYBxw
Good news is that the dissolved solids seem to trend with water intake and match B2 vitamin concentration in a dose dependent manner. Did you know that Zero Water sensors can measure in the ~10k range? They have a little 'x10' thing on their display.https://t.co/hXY7gqOteP
"molybdenum and sulfur combine in them to form compounds called thiomolybdates. These prevent the ruminants from absorbing copper. [...] However, the same chemical reaction has been used to develop a compound called tetrathiomolybdate (TM)." 1/2
"TM has the ability to reduce copper levels and is being researched as a potential treatment for Wilson’s disease, cancer and multiple sclerosis" 2/2https://t.co/9z7PgvRSjcOk, cool. Time to dig into molybdenum sources in my diet and see if it makes me not piss out all the b2.
That Healthline article cited this "Efficacy of tetrathiomolybdate in a mouse model of multiple sclerosis" [nov 2008]https://t.co/Tpa06V1YnaRelated: Cool Hunches.https://t.co/0bMv4CXic8
"Revisit gut microbiota and its impact on human health and disease" [JUL 2019] from 'Journal of Food and Drug Analysis' highlights some additional insights to the Molybdenum/bacteria related inflammation processes aside from butyrate/propionate levels.https://t.co/fDBTlr3w3E https://t.co/3k1ZS6hRT6
*fast*https://t.co/baNSAondNj https://t.co/ykZrNkmV9l
Acute Aestivation.Hedgehog Spirit.https://t.co/X8HpIj02Nh
@Mangan150 @jasonmpeirce @naval "This mirrors the effect of fasting and very low calorie diets, [...] but also can cause a form of glucose intolerance known as benevolent pseudo-diabetes. [...] it is associated with better health and life extension"https://t.co/zbkgmhEcSxYep, fasting. An Aestivation Trigger.
Have you tried fasting anon?https://t.co/mVSEsikLIp
I have no idea what I'm doing, but it seems to be working to make me healthier.https://t.co/6Imkfk1pdw
@benedict_rs I don't know of a good proxy for measuring fertility in women. I did notice that mTOR related pathways seem to improve implantation rates during artificial insemination procedures. But that's hard to measure without actually doing it. https://t.co/SE0AVVitqI
Its all because of my (obsession with my) autism.https://t.co/QLz04fHkC7
What is dendric sine and autism doing in a thread about Freud and constipation?And why would fasting help?https://t.co/cF5PqQ0b7u
Fasting => Gut bacteria shift => reduced gut inflammation causing less GI distress => reduced IL17 => lower glia cell response => improved improved dendritic spine morphogenesis.https://t.co/c4YxbEtdWF
I just pretend that Traumatic Brain Injury Recovery, and Multiple Sclerosis are the same thing, and then apply that model to Autism by way of gut problems.https://t.co/J704OEzZOm
"Fasting for 24 hr confers neuroprotection, maintains cognitive function, and improves mitochondrial function after moderate (1.5 mm) TBI. The underlying mechanism appears to involve ketosis rather than hypoglycemia."https://t.co/N7KBBUAb0BGotta go fast!
Sure seems like a whole lot of work to change your gut bacteria.https://t.co/yRmoQ3NsBH
Starting to really enjoy Molyhttps://t.co/GYMDDT33iG
Stinging Nettle; seems like such a wonderful plant. Helping get nutrients (like Molybdenum), adjust gut health, and fight candida at the same time.https://t.co/oK0H1DkEfG
GF has been having candida troubles for more than a year now. Trying to iterate toward a nutrient dense food stack to help make it easier to do fasting.https://t.co/dnsLFCRPqM
Someone recommended we pick up a cool book"Fast like a girl"https://t.co/URHeetNlLmhttps://t.co/DtzXISFiD0
The doctor behind it (Dr. Mindy Pelz) has some cool ideas on ways of dealing with menopause & nutrient timing that sounds promising.https://t.co/RUgs2qVxj3(GF's PCOS is like a pseudo-menopause)
Anyone else taking Moly* for hair loss?https://t.co/Tl13QFCevO
If only there was an easier way to reverse type II diabetes. Like maybe some kind of simple diet shift toward a gut profile that respects circadian rhythms and improves lipid function?https://t.co/dn1GfLukMv
Maybe a simple combination of traditional fermented foods that shore up missing microbes tied to fat digestion and absorption? Stuff like Kefir, Kombucha, and dishes like sauerkraut?https://t.co/Mp1mbYMaNB
@markeatsmeat @KetoCarnivore @AlpacaAurelius So I just did it faster by acting on the underlying mechanism that fixes bile acid pool size and function. Didn't want to wait years for my body to recover a healthy gut population.*sips tea*https://t.co/P1KEGfIgOL https://t.co/1FYX5FpJVd
I think teas that aid in gut health also could help, but we didn't end up using them until after my GF had already reversed her type II.https://t.co/2gvUmKeg9k
@sprague @KetoMojo @cronometer Specifically, any of the bacteria that seem to promote bile-acid pool size or act on FXR (farnesoid X receptor) and are resistant to bile.Good starter papers to begin exploringhttps://t.co/vZqyrKlAUyhttps://t.co/cOxWvjWlM0https://t.co/0n08awwFnLhttps://t.co/KLqkiWDA4malso
We didn't even do a keto diet on her. We mostly just cut added sugars and avoided gut disrupting foods (preservatives and synthetic emulsifiers etc). https://t.co/5eg4EP41uU
@worlddestroyar @Metabolic_Mind GF's gut health was seemingly fixed by eating Kefir + Kombucha and timing it well with her circadian rythym. While we did cut out added sugar, she was definitely not in ketosis.Found this out in fall 2022 when we got a CGM and she was't having insulin spikes from foods.
The candida she had was largely caused by the lung doctor giving her medication she should have never been on.The guy just said she needed to lose weight and that the medication can't do this... https://t.co/MJhiWGbw6F
I looked up the lung doctor to tell him thank you for fucking her up, because I never would have been in a position where giving her an FMT was actually the safer option.Turns out he died. :/https://t.co/rpkTJ9MOcP
Motherfuckers say what?https://t.co/yr0TQyzMJs
@ahandvanish Check out his review of a paper on using FMT to treat Fibromyalgia. https://t.co/4N6tsXTiiPLactate angle is fascinating , is interview online? I suspect brain lactate is a side effect a GI problem, reverse of gut lactate excretion we see in athletes. https://t.co/BBFE8dVa1Y