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Dean Pomerleau

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About Dean Pomerleau

  • Birthday 11/12/1964

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  1. Gordo, That's a really I interesting course of illness. Thanks for sharing your experience. Glad to hear that you are now really over it and that there don't seem to be any lingering symptoms and that your family is fine. Maybe if you had gotten a booster dose you would have avoided (symptomatic) illness like the rest of your family. Who knows. --Dean
  2. Dean Pomerleau

    Are we exercising too much!

    Mike Lustgarten created a very nice video (thanks Mike!) about this study, showing that the relationship of significantly increased mortality in those exercising more than 10 hours per week did not hold in never smokers, nor in people who had a normal BMI (i.e. less than 25.6), nor in women. See this post: --Dean
  3. Dean Pomerleau

    CR for elderly 80+

    Hi Geoff, See this entire threat for a discussion of the scientific evidence for risks associated with starting (and maybe continuing) CR in one's elder years: --Dean
  4. The study referenced earlier, that found strong evidence that Omicron evolved in mice for over a year before jumping back to humans, has now been peer-reviewed and published [1]. Here is the upshot: Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak. You may recall that in the original pre-print, the Chinese authors seemed to bend over backwards to avoid any hint that mice in question may have lived in a research lab, despite citing several studies (including some ongoing ones in the US) which are experimenting with serial passage of SARS-CoV-2 in laboratory mice. In the original concluding paragraph of the pre-print, they went so far as to stress the wild animal hypothesis: Our study suggests that SARS-CoV-2 could have spilled over from humans to wild animals, and that the variants which successfully infected animal hosts could then accumulate new mutations before jumping back into humans as a variant of concern. Given the ability of SARS-CoV-2 to jump across various species, it appears likely that global populations will face additional animal-derived variants until the pandemic is well under control. Viral surveillance and sequencing in wild animals will likely help to prevent future outbreaks of dangerous SARS-CoV-2 variants. Here is the newly published concluding paragraph: Humans represent the largest known reservoir of SARS-CoV-2, and frequently come in contact with other animals, including livestock animals, pets, or wild animals that invade homes searching for food and shelter. Given the ability of SARS-CoV-2 to jump across various species, it appears likely that global populations will face additional animal-derived variants until the pandemic is well under control. Our study thus emphasizes the need for viral surveillance and sequencing in animals, especially those in close contact with humans. Notice in the new final paragraph they expand the potential origin from "wild animals" to "livestock animals, pets or wild animals." Again no mention of laboratory animals, which seem of pretty obvious alternative possibility given that the authors are strongly implicating mice as the likely Omicron origin. It seems like a distinct possibility that the researchers involved in this study wanted to hint at the possibility of lab mice as the vector for Omicron (by their citation of studies of serial passage / gain-of-function researcher with SARS-CoV-2 in mice), without coming out and explicitly saying that lab mice are the most likely origin. Perhaps they realize how incendiary and controversial it would be if they suggested a lab leak or deliberate release of a laboratory-evolved variant to explain Omicron's origin, despite this seeming to me to be the most likely explanation for their findings. Very curious. --Dean -------------- [1] J Genet Genomics. 2021 Dec 23:S1673-8527(21)00373-8. doi: 10.1016/j.jgg.2021.12.003. Online ahead of print. Evidence for a mouse origin of the SARS-CoV-2 Omicron variant. Wei C(1), Shan KJ(1), Wang W(1), Zhang S(1), Huan Q(2), Qian W(3). The rapid accumulation of mutations in the SARS-CoV-2 Omicron variant that enabled its outbreak raises questions as to whether its proximal origin occurred in humans or another mammalian host. Here, we identified 45 point mutations that Omicron acquired since divergence from the B.1.1 lineage. We found that the Omicron spike protein sequence was subjected to stronger positive selection than that of any reported SARS-CoV-2 variants known to evolve persistently in human hosts, suggesting a possibility of host-jumping. The molecular spectrum of mutations (i.e., the relative frequency of the 12 types of base substitutions) acquired by the progenitor of Omicron was significantly different from the spectrum for viruses that evolved in human patients, but resembled the spectra associated with virus evolution in a mouse cellular environment. Furthermore, mutations in the Omicron spike protein significantly overlapped with SARS-CoV-2 mutations known to promote adaptation to mouse hosts, particularly through enhanced spike protein binding affinity for the mouse cell entry receptor. Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak. Copyright © 2021. Published by Elsevier Ltd. DOI: 10.1016/j.jgg.2021.12.003 PMCID: PMC8702434 PMID: 34954396 Conflict of interest statement: Declaration of Competing Interest The authors declare that they have no competing interests.
  5. Speaking of lab mice as a vector for covid, here is a troubling story of a researcher in a high security bio-lab in Taiwan contracting the first local case of covid in weeks after being bitten by a lab mouse infected with Covid. Not good. https://www.theguardian.com/world/2021/dec/10/mouse-bite-infected-taiwan-lab-woker-covid Whether or not Omicron originated as part of a lab experiment, the fact that gain-of-function research on SARS-CoV-2 using mice is not only a possibility but is being done successfully and pretty widely has disturbing implications. Unlike CRISPR manipulation of the genetic code, serial passage experiments that select for specific traits are quite low-tech. All it really takes is a colony of mice, access to the covid virus and a little patience. Not to be paranoid, but it seems to me that even non-state actors with nefarious intent could pretty easily use this technique to develop a new, more dangerous SARS-CoV-2 variant... This scenario reminds me of Nick Bostrom's thought experiment about what the implications would have been for the future of humanity if it had turned out to be possible to make a nuclear bomb by baking sand in a microwave oven: .... But suppose it had turned out that there was some technological technique that allowed you to make a nuclear weapon by baking sand in a microwave oven or something like that. If it had turned out that way then where would we be now? Presumably once that discovery had been made civilization would have been doomed. Each time we make one of these new discoveries we are putting our hand into a big urn of balls and pulling up a new ball---so far we've pulled up white balls and grey balls, but maybe next time we will pull out a black ball, a discovery that spells disaster. At the moment we have no good way of putting the ball back into the urn if we don't like it. Once a discovery has been published there is no way of un-publishing it. --Dean
  6. Thanks Brian. That is a fascinating paper. I don't pretend to understand all the genetic analysis they did, but from a relatively naive reading it looks like pretty significant support for the idea that the Omicron variant jumped from humans to mice, mutated for a while, and then jumped back to humans. The authors (strangely, IMO) seem to focus exclusively on the possibility that this sequence of jumps happened between "wild" mice and humans. They say in the conclusion: Our study suggests that SARS-CoV-2 could have spilled over from humans to wild animals, and that the variants which successfully infected animal hosts could then accumulate new mutations before jumping back into humans as a variant of concern. Given the ability of SARS-CoV-2 to jump across various species, it appears likely that global populations will face additional animal-derived variants until the pandemic is well under control. Viral surveillance and sequencing in wild animals will likely help to prevent future outbreaks of dangerous SARS-CoV-2 variants. while paradoxically citing studies like this [1] from researchers at the University of North Carolina showing the human SARS-CoV-2 virus can be deliberately evolved to lethally infect mice through serial passage experiments. Here is the graphical abstract from [1]: I'm no conspiracy theorist and I'm agnostic about the "lab leak" hypothesis for the original SARS-CoV-2 virus. But if these [Chinese, BTW] researchers really have shown as good evidence as they claim to support the conclusion that the highly-mutated Omicron variant originated in mice, which would have required it to jump from humans to mice and then back again, against the backdrop of several research groups (including but not limited to the UNC group above) conducting what I would characterize as "gain-of-function" research with SARS-CoV-2 using standard laboratory mice, it doesn't take a rocket scientist to put 2 and 2 together in order to see the possibility that Omicron may have originated in a lab. It is strange (to put it mildly) that the authors didn't even raise the possibility of a lab origin for Omicron in the discussion of their results. Heck, they didn't even mention mice in their concluding paragraph (using "wild animals" instead) despite the fact that the entire paper was about the evidence for mice being the specific likely species of origin, and not humans, rats, dogs, cats, cows or pigs which they also tested against. Bizzarely, they also didn't mention Omicron in their concluding paragraph, using "variant of concern" instead. They were more explicit in the abstract: Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak. Let me reiterate, I'm not qualified to assess the quality of the evidence supporting the authors mouse-origin theory for Omicron. But it seems to me the very existence of this preprint is almost guaranteed to set off fireworks about a lab origin for Omicron, despite its clinical tone and anodyne conclusion. --Dean ---------------------- [1] Leist, S.R., Dinnon, K.H., 3rd, Schafer, A., Tse, L.V., Okuda, K., Hou, Y.J., West, A., Edwards, C.E., Sanders, W., Fritch, E.J., et al., 2020. A mouse-adapted sars-cov-2 induces acute lung injury and mortality in standard laboratory mice. Cell 183, 1070-1085 e1012.
  7. No. That webpage has been updated in the past couple days to mention the new Omicron variant. Here is what it looked like back in July, when it discussed Delta as the new variant of concern: https://web.archive.org/web/20210712172008/https://www.weforum.org/agenda/2021/07/how-scientists-detect-new-covid-19-variants/ Omicron (B.1.1.529) was first detected this week. --Dean
  8. Hi Deniz, Welcome to the CR Forums. Your blood work looks quite good except for cholesterol. Barring something unhealthy about your diet or lifestyle that you haven't shared, I'd speculate your high cholesterol may be due to genetics. That appears to be the case for my wife, who is thin, eats healthy (nearly vegan), and exercises daily but still has LDL cholesterol around 130 mg/dL. She has one Apoe4 allele according to 23andMe, making her prone to elevated cholesterol. Does high cholesterol run in your family? Amla supplements gave her a modest benefit (see here) so that might be worth a try. Going back to a healthy vegan diet might help too. Otherwise you are probably left with stains or living with high cholesterol as your only two options. Good luck! --Dean
  9. Here is Michael doing a pretty good Aubrey de Grey impression, optimistic as ever that if hurry (and give lots of money to SENS) we can defeat aging before we all croak: https://www.mirror.co.uk/news/world-news/five-main-theories-achieving-immortality-25232041 --Dean
  10. Dean Pomerleau

    Postmeal hyperglycemia - how much is too much?

    Excerpts from past Michael posts on the evidence that large and/or prolonged postmeal glucose excursions are intrinsically harmful, especially for skinny people: One of the studies discussed there shows that if your glucose hasn't returned to its fasting level (or below) by 2 hours after a meal, you're at elevated risk of dying from CVD or any cause, even if your fasting glucose is within the normal range. --Dean
  11. Dean Pomerleau

    Postmeal hyperglycemia - how much is too much?

    Yes. Quite probably. No. Not necessarily. A short bout of post meal exercise is an alternative, quite effective means of blunting the post-meal glucose spike. --Dean
  12. Dean Pomerleau

    Fasting for CR Benefits?

    This new study in Nature Communications [1] found that tumor growth and metastasis in a mouse model of breast cancer were better controlled by daily, time-restricted feeding (20% CR, one meal per day) than in an isocaloric fasting mimetic diet (FMD) regime which consisted of cycles of 10 days with no restriction followed by 4 days of heavy restriction (30% of ad lib calories). They also found that a specially formulated mouse version of Longo's FMD diet (low carb & protein, high fat) was no better than an isocaloric amount of standard rodent chow when it came to preventing cancer growth. Of course as discussed earlier, once-per-day feeding in mice potentially equates to a 3-4 day fast between meals in humans, and the 10:4 FMD regime used here might equate to a month of no restriction followed by two weeks of eating 3000-4000 calories as a single meal once over 4 days. So it's not clear how relevant these results are for humans. --Dean -------------- [1] Pomatto-Watson, L.C.D., Bodogai, M., Bosompra, O. et al. Daily caloric restriction limits tumor growth more effectively than caloric cycling regardless of dietary composition. Nat Commun 12, 6201 (2021). https://doi.org/10.1038/s41467-021-26431-4 Abstract Cancer incidence increases with age and is a leading cause of death. Caloric restriction (CR) confers benefits on health and survival and delays cancer. However, due to CR’s stringency, dietary alternatives offering the same cancer protection have become increasingly attractive. Short cycles of a plant-based diet designed to mimic fasting (FMD) are protective against tumorigenesis without the chronic restriction of calories. Yet, it is unclear whether the fasting time, level of dietary restriction, or nutrient composition is the primary driver behind cancer protection. Using a breast cancer model in mice, we compare the potency of daily CR to that of periodic caloric cycling on FMD or an isocaloric standard laboratory chow against primary tumor growth and metastatic burden. Here, we report that daily CR provides greater protection against tumor growth and metastasis to the lung, which may be in part due to the unique immune signature observed with daily CR.
  13. Dean Pomerleau

    Fasting for CR Benefits?

    I finally thought to search these forums for Michael's perspective on fasting. In this thread from 2015: Michael makes the case based on the evidence available at the time that any observed benefits of intermittent fasting / time-restricted feeding results from calorie restriction and that intermittent fasting / time-restricted feeding in the absence of calorie restriction won't confer much benefit. Of course I can't speak for what he would say about the latest study we are discussing here. But if I had to guess, I think Michael would say: 1) The apparent benefits of ad-lib calorie intake within a limited 3h period each day were only shown to manifest as improved biomarkers. Improved biomarkers don't necessarily imply extended lifespan as other studies he cites in that thread have demonstrated. 2) The reduced lifespan of mice who consumed 30% fewer calories than AL in the form of fiber-diluted food eaten nearly continuously throughout the day may have either a) thrown off their circadian rhythm because in order to get enough calories they probably had to eat well into the part of the day when they are normally dormant and/or b) simply demonstrated that nearly continuous snacking throughout the day is unhealthy, a point he makes in one of the later posts in that thread. That is, you should give your body some time between meals where it isn't processing food, but especially long such periods aren't much (if any) better than shortish such periods, as long as you are calorie-restricted. It would certainly be interesting to hear his perspective on the evidence in favor of intermittent fasting and time-restricted feeding that has accumulated in the six years since he last posted to that thread. Unfortunately I don't expect we'll hear from him since he's probably quite busy dealing with the turmoil at the SENS Foundation... --Dean
  14. Dean Pomerleau

    Fasting for CR Benefits?

    That is most of the direct evidence I know of in favor of morning vs evening time restricted eating in people. But I haven't looked into the evidence lately. If the hypothesis I just outlined is true, namely that BAT and cold-induced thermogenesis may be important mediators for the apparent benefits of time restricted eating, than I would suggest further support for morning (vs evening) eating stems from the circadian rhythm of thermogenesis in humans, which is naturally high during the day and low at night. --Dean
  15. Dean Pomerleau

    Fasting for CR Benefits?

    You may be surprised to hear that you won't find me arguing against this hypothesis. In fact, after thinking about it, that may be exactly what's happening. As in almost all CR rodent experiments, these mice were housed at 70F (20-22C) temperature, which is many degrees below thermal neutrality for mice (~80F), which I discussed (ad nauseum) in the cold exposure thread. So if you are saying what I think you are saying, namely that feeding mice an AL amount of food in a narrow window of time and allowing them to burn off the extra via cold-induced thermogenesis during their long daily fasting period confers on them the metabolic, gene expression and potentially longevity benefits of CR, you won't get any argument from me. In fact that is a pretty good summary of the entire 500 pages of arguments and evidence on cold exposure thread! It is unfortunate that the researchers didn't measure thermogenic brown adipose tissue (BAT) in the three groups of mice. I would bet good money based on evidence presented in the cold exposure thread that BAT was elevated in the time restricted AL-fed mice relative to the other two groups. And note the opposite effect may explain the other arm of the experiment with the diluted CR mice dying earlier than even the AL mice. With 30% fewer calories than AL and no digestive downtime, the diluted CR mice may have been particularly bad at maintaining BAT and therefore generating heat, worse than either the AL-fed or the regular CR mice. As a result their health and longevity suffered despite eating fewer calories. But if that is the case (i.e. you can get the benefits of CR without the calorie deprivation if you eat a lot in a narrow window of time and burn the excess off via thermogenesis during the rest of the day) aren't you undermining your own (and Michael's) "Calories, Calories, Calories" mantra? --Dean
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