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You can invalidate Bret Weinstein's theories on telomere length being pleotropic by finding creatures that violate haystack limit and undermine Horvath's clock. And it becomes trivial to do from my model of hibernation.https://t.co/WsZXbzL1qc
Like ants using gut bacteria to deal with cancer, and hibernating ground squirrels telomers getting longer.Stop focusing on telomeres! Its a distraction.https://t.co/suTTPiJ5ip
Do you know what is also a poor representation of human models of disease? Mice's gut microbiome.If gut bacteria's impact on methylation drive telomere length via metabolism, then we don't need Pleiotropic factors to explain it.https://t.co/edqkXMY8ep
My what big telomeres you have.All the better to survive metabolic stressed tied to hibernation, my dear.https://t.co/WsZXbzL1qc
This way of looking at the problem also invalidates many model theories of cancer that also fetishize telomere length.This could be us!https://t.co/CBndACrMiG
WHAT COULD THEY MEAN BY THIS?https://t.co/yCJEMoSgRm
It's almost like we aren't testing accurate models of disease in lab mice. https://t.co/VZz8gKa8ao
Telomere length findings in mice are a red herring if you actually go an look at how methylation pathways impact genetic expression. Its all a fucking statistical error because we are all fucking idiots.https://t.co/ZGa7trdqtX
"Dr. Kannan says he and his colleagues were startled by these observations."https://t.co/hE5M0Y6oByFIX YOUR FUCKING MODELS. 🤬https://t.co/pk9TFlcSMB
What is an edible dormouse and why should you care about how it's telomere length coincides with food availability and it's hibernation cycle?https://t.co/MbMRenCNYMhttps://t.co/smgXY3YNXA
1) why do we know Romans ate this weird mouse.2) "edible dormouse" is really on the nose eh?3) if it's so good at hibernating, it suggests romans lived in areas that required hibernation!4) why would we be looking to see if Romans had similar rituals?https://t.co/c4C64GEfdT
Please take a closer look at how we keep fucking up models of aging and cancer because we just assume lab mouse studies are gospel.https://t.co/oTVdI5FBEP
"Surprisingly, and contrary to our hypothesis, telomeres were shortened only in younger dormice but were elongated in older animals. To our knowledge, no other longitudinal study on humans or other animals has reported such an effect."https://t.co/MbMRenCNYM
Maybe it's the gut microbiome?https://t.co/3bhxeCHNcF
“The contents of the gut were thought to putrefy and release toxins through the action of bacteria. Physicians were attributing anything from headaches and fatigue to heart disease and epilepsy to these toxins”https://t.co/SjNC0x4bEwhttps://t.co/ciEFxucixK https://t.co/Zibbo3Irm2
Learn about the theories of Élie Metchnikoff, Nobel Prize Winner who worked along side Louis Pasteur, in this great talk by @ruairirobertson https://t.co/56tANAJZVmHis ideas are effectively an early version of gut dysbiosis of the a in the 1900s. https://t.co/Lqx3WSLT7I https://t.co/tOPVJ5snTS
Wait, you mean a society caught in the grip of the derangement of psychology somehow overlooked an essential aspect of our biology, and our science process hasn't been modeling it at all because it was dismissed as ludicrous? Nah, must be the telomeres.https://t.co/K2vRJyVUs5
"This is probably not because madness never produced excremental behaviours of this kind. The question then is why did this only result in a meaningful medical category of behaviour from the late nineteenth century onwards?" https://t.co/36aCsUEHrI https://t.co/5B8upkOvyN
I bet they were smelling gas coming up from people's stomach & correlated bad smells coming from gut microbes with diseased states?Lots of disease has a distinct odor. https://t.co/ayTvKJMcRoSo it seems reasonable to assume microbial toxins?https://t.co/fofRbxHKWs
"Abnormal shifts in the gut microbiome, however, have been implicated in the pathogenesis of age-related chronic diseases, including obesity, cardiovascular diseases and neurodegenerative diseases. [...] emerging as a key factor in the aging process."https://t.co/8pOrQElB7L
All that said, I agree with Bret's conclusions that the mouse models we've built is just batshit insane and have so much room for faulty conclusions you could drive a bus thru it.https://t.co/2SCWQnI7ME
"We also reproduced the previous finding on reduction in regenerative capacity in limbs of axolotl following metamorphosis, highlighting the need to investigate whether shifts in microbiota is causally linked to regenerative capacity of axolotl."https://t.co/zmp7k9nivl
*laughs*"Thus, the balance between inhibitory and necessary immune responses for regeneration appears to be highly regulated and warrants further exploration."https://t.co/fYTVEiYdb6 https://t.co/67NMrSqQaq
BRB learning to breed salamanders.https://t.co/qgSqfp0Pkp
What's telomeres precious.What's telomeres eh?https://t.co/q7qvz69gPO
Did you know that bears are able to heal some wounds during hibernation. They also grow bones.https://t.co/zrWCWO3DwQ
I learned this by way of native American animal lore.What else are we overlooking?What else might "scientists haven't noticed before"?https://t.co/xb6dAsayQv
"As the strange folk mined deeper and deeper into the mountain, holes began to appear, bring with them a cold and bitter wind that chilled the very soul of the monkey." 🎶https://t.co/RFcuhEzBjk
"the initial reports by Yamanaka and others on transcription factor (Oct4, Sox2, Klf4 and c-Myc) directed re-programming of somatic cells to a pluripotent state showed that this event is accompanied by telomerase activation and telomere length extension"https://t.co/auJVKaDXuR
So that bit where I learned about echidnas actually paid off. And thanks to some interesting findings on royal jelly induction of pluripotent states (thanks @mmmalign ) I might even have a bead on how to induce it with microbiota. https://t.co/9ig1NnPxBhhttps://t.co/4wanmDeCES
My, what healthy gut microbiota you have.Why, all the better to induce and direct healthy pluripotent states with, my dear.https://t.co/gADZqOBvB1https://t.co/ciEFxucixK
Learn about the theories of Élie Metchnikoff, Nobel Prize Winner who worked along side Louis Pasteur, in this great talk by @ruairirobertson https://t.co/56tANAJZVmHis ideas are effectively an early version of gut dysbiosis of the a in the 1900s. https://t.co/Lqx3WSLT7I https://t.co/tOPVJ5snTS
"Novel strategies already employed to improve reprogramming include the inhibition of barriers to reprogramming, use of non-integrative delivery methods, overexpression of enhancing genes and the use of certain small molecules which enhanced reprogramming"https://t.co/B4o8jOG1V5
"The results of such mouse experiments, while tantalizing, were also frightening. Depending on how much reprogramming occurred, some mice developed ugly embryonic tumors called teratomas, even as others showed signs their tissues had become younger."https://t.co/aQGHMJyhXsLMAO
To think what I could do if I had actual funding.https://t.co/GmkY0t108N
Did you know garlic extracts might impact telomeres and as a result be effective at fighting forms of gastric cancer?"Allicin can inhibit telomerase activity and induce apoptosis of gastric cancer SGC-7901 cells. Allicin may be more effective than AZT"https://t.co/rlnIB4oDXy
Next you'll be telling me that ancient medical traditions used garlic to treat cancer. https://t.co/otdxmCDofn
"The overall findings may suggest that intakes of aged garlic are inversely associated with cancer. [...] more precise investigations will be necessary to decide whether aged garlic consumption is recommendable as a part of cancer prevention or control"https://t.co/q2usx0oTVf
About running circles around the existing institutions simply by paying heed to the past. Gotta go fast.https://t.co/K3vF0WesfE
"Recent studies indicate that telomere length, which can be affected by various lifestyle factors, can affect the pace of aging and onset of age-associated diseases." 😂https://t.co/dig4n4MX0I
Abnormal DNA methylation, in my cancer cells?"Overall, this study reveals highly significant relationships between two hallmarks of aging: telomere biology and epigenetic changes."https://t.co/E7ozkADbK8https://t.co/hcpMvJfzXZ
"Methylation within the promoter regions of tumor suppressor genes causes their silencing, and methylation within the gene itself can induce mutational events. [...] may play a fundamental role in [...] a large and diverse number of human cancers."https://t.co/anCydJshwF
"Epigenetic changes are considered to be among the earliest and most comprehensive genomic aberrations occurring during carcinogenesis"https://t.co/UzPBWEMrHBGosh.
"In this review, the links between CBD and the interplay canonical Wnt/β-catenin-PPARγ in [Alzheimer's Disease] are discussed." [2017]https://t.co/SioawEcEsq
"This review focuses on the potential effects of lithium, as a potential therapeutic strategy, on [Parkinson's Disease] [...] Lithium medication downregulates GSK-3beta, the main inhibitor of the WNT/β-catenin pathway. " [2021] https://t.co/IMW1rM2jfy https://t.co/4zi3el4yvk
"The first mood stabilizing medicine lithium was discovered serendipitously; [...] Since then an ever increasing body of work has elucidated the roles of GSK3 and the associated Wnt pathways in mood disorders and several other neuropsychiatric ailments." https://t.co/0RcfJyF3k7
Manic Depressive. Bipolar. Autism. Schizophrenia. Neurodegenerative disease?https://t.co/u3hfOcpBHC
I'm not crazy."this case supports the need to consider MS in patients with manic symptoms and with neurologic findings that occur later in the disease course. It also highlights the need to specifically address underlying causes of psychiatric symptoms."https://t.co/5nHt2IIQjz
Does lithium help with autism because it acts on WNT/β-catenin pathways associated with brain development genes?https://t.co/apeItzccK4
Heh"Wnt signaling networks in autism spectrum disorder and intellectual disability" [2016]https://t.co/h3dx9v5njb"Wnt/β-Catenin-Dependent Transcription in Autism Spectrum Disorders" [2021]https://t.co/7TeMhbcM9Mhttps://t.co/XS3iwOfqCC
L M A O"Wnt/β-Catenin Signaling as a Molecular Target by Pathogenic Bacteria"https://t.co/ByXaVtE5Fx
:hand-clapping-emoji:https://t.co/18HdxprafP
" In this review, we examine the different ways human bacterial pathogens with distinct host cell tropisms and lifestyles exploit Wnt signaling for infection and address the potential of harnessing Wnt-related mechanisms to combat infectious disease."https://t.co/AT1LLDO1yD
"mood stabiliser lithium and the antidepressant fluoxetine, influenced the composition and richness of the gut microbiota. Although some [...] drugs have been previously investigated in in vitro settings, this is the first evidence in an animal" [2019]https://t.co/z6crEpCft1 https://t.co/mKN2FwQwZa
"We replicated previous findings that children and adolescents with autism spectrum disorder (ASD) have shorter telomeres, compared to typically developing (TD), and show that unaffected siblings have telomere length (TL) in between those of TD and ASD." https://t.co/pkJ0SRJLQb
"Telomere Dysfunction"🙄"Although conceptually appealing to explain proliferative exhaustion and cell ageing, telomere shortening is inadequate to explain ageing in non-proliferating, quiescent or terminally differentiated cells."https://t.co/q9RSwPI5GI https://t.co/SICS4XplOv
Tired: Telomere DysfunctionWired: Incomplete Hibernationhttps://t.co/46XeBX1FP8
Haha #eatshit, it worked.https://t.co/sxktFUZszI
"If you can turn a gene on with a nutrient like royal jelly, you might be able to turn it off with another. The idea that we could control these semi-permanent epigenetic changes with diet is remarkable." https://t.co/jEEnq179C0💅https://t.co/awmtujjoUs
That's the plan.https://t.co/VA3kGp1P7v
Shot"Our study shows that structural components of the bacterial microbiota can be directly sensed by hypothalamic neurons to regulate feeding behavior, nesting behavior, and body temperature."https://t.co/Jguh2KG5XFhttps://t.co/p4gNmOs8GW
Chaser"Given that there are substantial differences between captive and wild environments, conclusions drawn from studies with captive hibernators may not reflect the gut microbiota’s role in the physiology of wild animals."https://t.co/6Wfqx9S5N0https://t.co/HhCphPFvuH
@LorentzianJelly Looks like I got some stuff to read that study on NOD2 response to environment is cited in this study on hibernation, published in january 2022. (citation 47)It's saying that we don't know shit about gut bacterial hibernation in wild species.https://t.co/6Wfqx9S5N0 https://t.co/382XpvOLso
I bet not.https://t.co/BKJO9LI56G
Epigenetic impacts of gut bacteria sensing genes in Irritable Bowel Syndrome, Impacting my Telemers?More likely than you think.https://t.co/AKrPoOByh9
"a microbiome dominated by potential commensal bacteria [...] larger telomeres, [suggests] early establishment of the species-specific microbiome during development may have important consequences on offspring health and survival." https://t.co/cSowXGxU6T https://t.co/hoCbd1H9x8
"Growing evidence suggests that hTERT also contributes to the cell physiology independently of telomere elongation. However, its role in bacterial infection is unknown."https://t.co/KWu24MVvJY
"H. pylori inhibits TERT gene expression and decreases the telomerase activity. The exposure of cells to lycopene, an antioxidant compound, restores TERT levels in infected cells, indicating that ROS are implicated in this downregulation." https://t.co/iJGLrIW0k9
"Cells lacking hTERT exhibit increased radiosensitivity, diminished capacity for DNA repair, and fragmented chromosomes, demonstrating that loss of hTERT impairs the DNA damage response." https://t.co/vG0KhfLAeF
"These results identify hTERT as a direct target of the HH signaling pathway, and reveal a previously unknown role of the HH/GLI axis in regulating the replication potential of cancer cells." [2013]https://t.co/5ZDgkWxeEL
"The TargetScan database and the MetaCore software functional annotations of predicted targets revealed crucial signalling pathways downstream of the TERT/miR500 cluster axis, including the Wnt/β-catenin, NF-κB and Hedgehog pathways, among others."https://t.co/oUcspqYkSj https://t.co/crYDM4A684
Nothing about miR500A here. Is no one looking for it?"Here, we will review current findings of the interactions between the gut microbiota and microRNAs and discuss how the gut microbiota–microRNA interactions affect host pathophysiology" https://t.co/K7JAwQZeMh
Hedgehog Aestivation?"This study demonstrates for the first time, hypoxic regulation of TERT expression in vivo in a whole fish system. [...] Overall, the structure and regulation of the TERT gene is highly conserved in vertebrates from fish to human." https://t.co/yfjetQguMR
Oh, hello there. This is also suggesting that we can use xenotransplantation to cause hibernation it in mice via modulating a gut->TMAO pathway?https://t.co/5XvHdYaTJlIt turns out that captive bears fail to hibernate pretty often.https://t.co/yOg3lpWALe https://t.co/LTxK3QnHBf
What destroys their gut?Is it that we give antibiotic pharmaceuticals to captive stressed bears?https://t.co/im7jxsEUvm
Fluoxetine? Get rekt son."pathways are functionally-relevant downstream drug effects and are also activation pathways for telomerase, suggesting a potential (yet unproven) mechanism by which these drugs may mediate neurogenesis via telomerae activation" https://t.co/QN1cidgZDl https://t.co/2xGYBA356Q
What is in the water?https://t.co/gPxadQksbJ
Can humans hibernate?Do you think it's full of weird dreams?Do you wonder if we can't because our guts are fucked?https://t.co/wzPPrkCfOQ
What happens if you use SSRIs and Pesticides to destroy the gut microbes that help hibernating ground squirrels exit hibernation? Do they never leave it? Do they get age related disease? Do they experience metabolic & mitochondrial dysfunction?¯\_(ツ)_/¯https://t.co/mdB51vDpLQ
Does Fluoxetine modulate Telomerase in germ-free mice? What about mice who eat bear shit?This is the kind of thing I'd want to try to study with the help of @newscienceorg https://t.co/T2QqiCkZW0
What is a dust fly?https://t.co/YNVPUCNsJR
@slay_ad @Cortexyme We read Ancient Sumerian tablets on recipes for fixing disease and assume they're just food recipes, overlooking them. "You shall eat still hot bread and the buttock of a donkey stallion stuffed with dog poop and the excrement of dust flies."https://t.co/bSXRvgapCK
I predict things.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
"[Myotis myotis] bat apparently does not express telomerase [...] epigenetic alterations, intercellular communication, and adult stem cell exhaustion, remain unaddressed and are also fertile grounds for further research." https://t.co/srFc59VIEy https://t.co/r9KxLB7YWy
"During the 20th century, this species was very rare in Great Britain, occurring only in southern England. However, the bats at the only known hibernation roost declined [...] and when these disappeared the species was believed locally extinct. However," https://t.co/lnzPoakCGr
What happens if you feed a mouse-tailed bat some antibiotics/antifungals. Does it not hibernate?https://t.co/mZrqiIk2aPhttps://t.co/iLRpn9W6X4 https://t.co/RvtpogBUhG
"Together, these data suggest that long lifespan in some bat species might be regulated by very efficient maintenance of protein homeostasis." https://t.co/gLclsmv0kN
"Understanding circadian regulation of mammalian cell function, protein homeostasis, and metabolism"https://t.co/NgAA0ev0T4"Much circadian cell physiology may be explained by rhythms in [mTOR] complex activity." 😏https://t.co/hZAwQg51gd
"bats exhibit lifespans that can be 3.5 higher than non-flying mammals [...] Six types of bats can live for three decades in the wild: Plecotus auratus, Myotis lucifugus, Myotis brandti, Myotis blythii, Rhinolophus ferrumequinum and Pteropus giganteus" https://t.co/QG9Ohmkuib
My prions, my prions. I am pained at my very gut ; my gut maketh a noise in me; I cannot hold my peace, because thou hast heard, O my gut bacteria, the sound of the farts, the alarm of telomeres.https://t.co/hOSN7Zn0yQ
"While at the organismal level, biological aging can be estimated by telomere length and DNA methylation signatures, reliable biomarkers that can predict reproductive age are much needed to gauge the quality of an oocyte." https://t.co/xSn9IZWWJm🥚👀https://t.co/6jpFZislXv
"Natural mammalian hibernation was continuously maintained under laboratory conditions throughout spring and summer seasons in a colony of thirteen-lined ground squirrels by serial transfusional passage of blood from hibernating animals to active animals." https://t.co/BIDhCVPb3F
"Age did not have a significant effect on [relative telomere length] in any tissue. At mid-hibernation, [relative telomere length] of juvenile females was longer in [brown-adipose tissue] and [skeletal muscle] than in liver and heart."https://t.co/8WqJjTSCQY
I just keep predicting things. https://t.co/6aBycqLlKR
Space travel disrupts DNA. Requires focus on DNA repair. https://t.co/BOqh4GRq77
Shame NASA didn't have good controls for those microbiome Twin tests.https://t.co/uD4yUAIry4
I am trying to become immortal.https://t.co/VxZiH0KiA9
Which means I need to learn about how hibernation repairs DNA.https://t.co/mQJzK4858j
And why scientists are so focused on DNA.https://t.co/YiKaJrADGG
Get Rekt. Do you even lift? I don't.https://t.co/dKmwhNrYcx
Do you think we could bootstrap DNA repair in astronauts by having them eat cannabis butter?Would be funny if the thing impairing their DNA repair are the drug tests they are given.https://t.co/bXqrw2ARQg
I just put random terms into google over and over again until I get angry at people being idiots.This is one of the ones that made me angry.https://t.co/5Y2MFfWwav
Idiots all the way down TBH.https://t.co/JSijfEOvgp https://t.co/1kUDUV6BPm
herp derp, this drug gets you high! that is bad boo!!! SPACE GOOD. I AM SCIENCE MAN! Helth. Helth.Meanwhile....https://t.co/nD6uX4HdCx
DNA damage from*checks notes*Acetaldehyde can be mitigated by many pathways.https://t.co/ECf4o8GCHd
I wonder if space travel leads to candida infections. We would be overlooking vaginal yeast infections simply due to the relatively low number of female astronauts.https://t.co/5vQxFwbuCc
What, you don't think about yeast infections in space and their impact on DNA damage? Why not?https://t.co/rlHKgzGnAI
You can get your immune system to regenerate tissue if you stop inflammation from fucking it up.https://t.co/iHx5Ml0rYE
Have you ever tried to fix your lipid signaling game via gut bacteria, so your body can produce SCFAs and digest omega fatty acids to better produce endocannabinoids and combat inflamamtion... And then suddenly all your health problems just disappear? https://t.co/l9WQjcM4Go https://t.co/lFxq0kgsn1
I have no idea what I'm doing.https://t.co/524lnuCp23
Ya'll want some garlic?https://t.co/IamQEvroUk
@stevebloom55 @DanielleFong oh look"Garlic supplementation by improving inflammatory mediators and clinical symptoms can be considered as a potential adjunct treatment in patients with RA. However, further studies with larger duration are needed." https://t.co/77o1hRoNF8
Or maybe you don't like the fire element in your diet. Maybe instead try fermenting beans for years instead. That works too.https://t.co/EEYjO3S1W7
@nosilverv @no_identd I'm learning about Ancient Sumerian and ancient Egyptian's use of garlic. Comparting it to Viking + European fermentation rituals involving garlic, leek, and onions, and then looking toward charka's colors as inspiration for food in Korean Temples. https://t.co/So1uEzEaBl https://t.co/CzjVKiHSk6
> "Our findings causally link mTOR-related synaptic pathology to large-scale network aberrations, revealing a unifying multi-scale framework that mechanistically reconciles developmental synaptopathy and functional hyperconnectivity in autism." [OCT 2021] https://t.co/6gnoDTTHcJ
consider this tweet, from APR 2021https://t.co/AwvGoAxN2o
I thought it would be funny to not age. It turns out that turtles do this by hibernating. It's why sailors would keep them on their ship as a food source. They can last a long long time without eating.https://t.co/SMqgFKoCtV
Everything flows from the great turtle.https://t.co/ZsR8oShdYn
While you're wondering about telomeres. I'm wondering about getting turtles drunk and what happens if you eat their poop.https://t.co/uN4zZWxhyh
Its fascinating how often fixing Alcohol associated liver problems ends up impacting telomere length.https://t.co/XLavVUxw4F