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Dean Pomerleau

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About Dean Pomerleau

  • Birthday 11/12/1964

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  1. Dean Pomerleau

    Haemoglobin levels

    Shezian, I've been vegan for ~18 years. My serum iron is always in the normal range, but both my haemoglobin and ferritin tend to be near the bottom of the reference range (e.g. ~13.2 g/dL for haemoglobin and ~30 ng/mL for ferritin). I do supplement with iron (65mg elemental iron twice per week), mostly because I donate blood every 3 months and if I don't my haemoglobin will be too low to qualify, especially for double red donation. After I donate (esp. after double reds), I definitely notice that my aerobic capacity is reduced for a week or so while by haemoglobin regenerates. But I never get sick. If your haemoglobin is lowish but near the bottom end of the reference range and you aren't experiencing symptoms of anemia (e.g. low energy, unusual shortness of breath / "heavy legs" climbing stairs), I'd say your illnesses and lower haemoglobin are probably unrelated. On the flip side, as pesco-vegan with weird haemoglobin, I don't think it would be unreasonable for you to consider modest iron supplementation - e.g. an RDAs worth of iron ever couple days. --Dean
  2. For anyone with a strong urge to try an unproven anti-aging therapy and a spare million bucks, a company called Libella Gene Therapeutics (headquartered in a strip mall in Manhattan Kansas) will enroll you in their gene therapy "clinical trial" which aims to lengthen your telomeres, similar to one of the treatments that Liz Parrish from Bioviva attempted on herself. Here is a description of the trial: https://onezero.medium.com/scientists-dodge-fda-to-offer-a-1-million-anti-aging-treatment-in-colombia-38756dfb3ad1 If it were free, would anyone here sign up for this experiment? While I admire the pioneering spirit of someone who would, given the lack of evidence that longer telomeres is associated with slower human aging [1] and the risk that it may increase cancer rates, I would give it a pass. --Dean ----------------- [1] Aging Cell. 2019 Dec;18(6):e13017. doi: 10.1111/acel.13017. Epub 2019 Aug 24. Telomere length and aging-related outcomes in humans: A Mendelian randomization study in 261,000 older participants. Kuo CL(1), Pilling LC(2), Kuchel GA(3), Ferrucci L(4), Melzer D(2)(3). Author information: (1)Department of Community Medicine and Health Care, Connecticut Convergence Institute for Translation in Regenerative Engineering, Institute for Systems Genomics, University of Connecticut Health, Farmington, CT, USA. (2)Epidemiology and Public Health Group, University of Exeter Medical School, RILD Level 3, Royal Devon & Exeter Hospital, Exeter, UK. (3)Center on Aging, School of Medicine, University of Connecticut, Farmington, CT, USA. (4)National Institute on Aging, Baltimore, MD, USA. Inherited genetic variation influencing leukocyte telomere length provides a natural experiment for testing associations with health outcomes, more robust to confounding and reverse causation than observational studies. We tested associations between genetically determined telomere length and aging-related health outcomes in a large European ancestry older cohort. Data were from n = 379,758 UK Biobank participants aged 40-70, followed up for mean of 7.5 years (n = 261,837 participants aged 60 and older by end of follow-up). Thirteen variants strongly associated with longer telomere length in peripheral white blood cells were analyzed using Mendelian randomization methods with Egger plots to assess pleiotropy. Variants in TERC, TERT, NAF1, OBFC1, and RTEL1 were included, and estimates were per 250 base pairs increase in telomere length, approximately equivalent to the average change over a decade in the general white population. We highlighted associations with false discovery rate-adjusted p-values smaller than .05. Genetically determined longer telomere length was associated with lowered risk of coronary heart disease (CHD; OR = 0.95, 95% CI: 0.92-0.98) but raised risk of cancer (OR = 1.11, 95% CI: 1.06-1.16). Little evidence for associations were found with parental lifespan, centenarian status of parents, cognitive function, grip strength, sarcopenia, or falls. The results for those aged 60 and older were similar in younger or all participants. Genetically determined telomere length was associated with increased risk of cancer and reduced risk of CHD but little change in other age-related health outcomes. Telomere lengthening may offer little gain in later-life health status and face increasing cancer risks. © 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. DOI: 10.1111/acel.13017 PMCID: PMC6826144 PMID: 31444995
  3. Dean Pomerleau

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    Tom, That depends. If you were to choose to start helping people (e.g. homeless people) rather than animals, would you still feel morally obliged to carefully vet each one to make sure he/she is deserving of your assistance and not some kind of criminal? That attitude would seem to preclude either charitable giving or direct volunteering, so it might be better to stick with helping animals. --Dean
  4. Dean Pomerleau

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    Ron, For once we agree! 🙂 But Tom is older than we are. If he feels he doesn't have time to wait and wants to play the lottery with one of the unproven and potentially deleterious treatments available today, I don't think it is an irrational choice. Tom knows the chance of these treatments making a dramatic difference is pretty low, but you shouldn't discount the psychological and QoL benefits of knowing you've left no stone unturned. --Dean
  5. Dean Pomerleau

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    Thanks Tom, I totally understand your thinking - you might as well try something and who knows, a novel regime of pulsed metformin + rapamycin might turn out to have dramatic health and/or longevity benefits. But it leaves me wondering whether you considered senolytic therapy instead of or in addition to your met + rapa strategy. Regarding us healthy people using up scarce medical services better spent on people who are actually sick. I agree with you. I've skipped my last couple yearly checkups with my GP and instead buy lab tests myself whenever I want to get insights into my health status. I can often get much more comprehensive lab tests done paying out of pocket to a place like LEF or Direct Labs than paying my insurance co-pay on a doctor's visit plus the lame list of standard bloodwork he'll order. Regarding your larger question: My answer is yes, spending a lot of time on life-extension minutia is being self-indulgent and yes, I believe it is worth spending more time helping others. Personally, over the last several years I've redirected a lot of the inordinate amount of time I used to spend posting here into pursuits that I think more directly impact people's lives in a positive way. Tom, I'm curious, are you and your wife still actively involved in animal rescue efforts? That certainly seems like a worthwhile, other-centered pursuit. --Dean
  6. Dean Pomerleau

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    As an addendum to my post from this morning, last week Reason from "Fight Aging" summarized a talk he recently gave on self-experimentation. He seems to agree with me that the risk/reward tradeoff for metformin makes it not worth taking and that the existing senolytic agents (dasatinib + quercetin) are likely a better option. Here is a quote from that talk summary about the four types of self experimentation: We might consider four classes of self-experimentation at increasing levels of sophistication. Class 1: the sort of thing that everyone does with dieting for weight loss or eating foods and supplements for benefits. Class 2: compounds that are easy to obtain, easy to use, have great human safety data, and that may have effects on aging, such as metformin (a poor idea, I think) or senolytics (a better prospect). Class 3: treatments that are logistically challenging, and that may need a personal lab. Few people would be able to safety inject themselves with myostatin antibodies, for example. Get that wrong, and you die. But it is technically plausible, and helpful in terms of spurring muscle growth, given the evidence. Class 4: treatments that require a company or other significant effort to create. Liz Parrish's efforts with Bioviva , in order to self-experiment with telomerase gene therapy, for example. Or cryonics, for that matter. In near all cases, from dieting to quite sophisticated efforts, people tend self-experiment poorly. They do not do the one fundamental thing, which is to measure the effects. In the "a poor idea, I think" link, he says: This review paper more or less leans towards my thoughts on metformin as a treatment to slow aging: the animal data is not great, the human data is a single study, the effect size on life span is far too small to care about, and the detrimental side effects are large in comparison to that effect size. --Dean
  7. Dean Pomerleau

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    Tom, I think we agree more than we disagree. I agree that we have tenuous evidence that many of the interventions you and/or I practice will positively impact our long-term health or longevity, beyond the basics like eating a healthy, mostly plant-based diet in moderation, engaging in moderate exercise and avoiding things that are known to shorten life like smoking. In the "speculative interventions" category (as far as humans are concerned) I would include calorie restriction, "optimal" nutrition, cold exposure, fasting/time-restricted eating, and vibration therapy. For the above listed speculative interventions, I think there are sufficient hints from the animal evidence and the limited human evidence that they may be beneficial, and most importantly that there is little evidence for downsides, at least in the doses and protocols that you and/or I have chosen to practice them. I think where we may disagree is over whether there is sufficient evidence to support the idea that the potential benefits outweigh the risks when considering adding pulsed metformin to one's regime starting relatively late in life when one is already quite healthy and practicing moderate calories restriction. As far as I can tell, there is no evidence that metformin benefits healthy people, to say nothing of healthy people already practicing CR (in whom presumeably mTOR activity is downregulated already), to say nothing of older healthy people already practicing CR. Similarly, as you suggest, pulsing metformin may be better, but then again it may be worse and we have no evidence (even in animals), one way or the other. You once said "primum non nocere" or "first do no harm". It seems to me the potential risks associated with metformin that you've identified outweigh the potential benefits, even if one takes a very optimistic interpretation of the rodent data on metformin and given the lack of evidence that pulsing metformin will preserve any benefits while mitigating the risks. But as you say, YMMV. Where I am in wholehearted agreement with you is that it's worth trying something different from the usual approach to aging and to life more generally. This is speculative so correct me if I'm wrong, but I think the difference between you and me may be that you seem pretty focused on the personal benefits that may accrue if you chose your regime wisely. I, on the other hand, am wired to as I've said before "go out on a limb" with my very usual regime simply to explore a part of the space of human possibility that has seldom if ever been visited, whether it works out well in the end for me or not. In short, I see value in being different for the sake of being different, as long as I'm not hurting anyone else by doing so, and I think there is a reasonable chance I'm doing myself more good than harm, and as long as there is the potential for me or others to learn something from my non-conformity. In fact, I think the ultimate purpose in life is to rationally explore the "adjacent possible" - things (or combinations of things) that nobody (or very few) has tried before. I'd rather push the envelop to see what's possible, and what works (or doesn't) in hopes that others will benefit from my exploration and experimentation. This has gotten pretty philosophical, so I'll stop there and return to the topic of the post. But for anyone new interested in the philosophical stuff, here, here, here, here and especially here and here are discussions about my philosophy of being inclined to "go out on a limb for a worthy cause." Gambling that pulsed metformin started late in life in someone who is already healthy and practicing CR is an example of going out on a limb in a new or seldom explored, potentially fruitful direction that I generally approve of. So kudos for that. The reason I personally wouldn't chose to start taking metformin now based on the available evidence is that I don't think it is likely to add more than a few months (at best) to the healthspan/lifespan of an older person who is already healthy and who has been practicing long-term moderate CR, like you and me. Such a small effect is unfortunate both because it confers little benefit on the person doing it, and because it will be so small as to be lost in the noise and therefore fail as a guide for anyone else. It's just going to be too little, too late, I'm afraid. If there were absolutely no hints of negative side effects, I might think even a few months extra might be worth it, and start taking metformin (+ rapamycin) myself. But downregulating mTOR is not something to be triffled with, and both drugs have clear hints of potential downsides (for muscles and brain at least), as you yourself have pointed out. If I thought it was time to throw caution to the wind and gamble on an unproven intervention with promising early results and modest potential for negative side effects, rather than metformin + rapamycin, I think I might gamble on the senolytic cocktail of dasatinib + quercetin which shows promise in rodents and older humans, particularly since I think I'm already getting most of the potential benefits of met + rapa from my practice of CR. That's why doing a more quantitative risk/benefit analysis like I was suggesting has merit, because it might allow you to rationally assess which interventions are likely to give you personally the most bang for your buck given your circumstances and existing practices. --Dean
  8. Dean Pomerleau

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    As an addendum to my previous post, the best available rodent evidence [1] suggests lifelong metformin doesn't extend lifespan at all in mice relative to ad lib fed controls. If you get the doses right, lifelong metformin + rapamycin appeared to extend median lifespan by 23% compared to controls, although the combination was only borderline statistically significantly different from the life extending effects of rapamycin alone. Interestingly, the original research on metformin and longevity [2] from 2013 found a very modest (~5%) increase in mean lifespan for the right dose in one strain of mice, but no statistically significant increase in another. Plus, they found too high a dose of metformin decreased mean lifespan by ~15%. So the assumption in my calculation of a 20% boost in rodent longevity from metformin was generous, to put it mildly. But 20% improvement from the combination of metformin and rapamycin (which it sounds like you are considering Tom), may be in the right ballpark, assuming you start taking them at the human equivalent of age 35, get the dosages right, aren't already getting the same benefits from practicing CR, and happen to be a mouse :-). --Dean ------------ [1] Aging Cell. 2016 Oct;15(5):872-84. doi: 10.1111/acel.12496. Epub 2016 Jun 16. Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. The National Institute on Aging Interventions Testing Program (ITP) evaluates agents hypothesized to increase healthy lifespan in genetically heterogeneous mice. Each compound is tested in parallel at three sites, and all results are published. We report the effects of lifelong treatment of mice with four agents not previously tested: Protandim, fish oil, ursodeoxycholic acid (UDCA) and metformin - the latter with and without rapamycin, and two drugs previously examined: 17-α-estradiol and nordihydroguaiaretic acid (NDGA), at doses greater and less than used previously. 17-α-estradiol at a threefold higher dose robustly extended both median and maximal lifespan, but still only in males. The male-specific extension of median lifespan by NDGA was replicated at the original dose, and using doses threefold lower and higher. The effects of NDGA were dose dependent and male specific but without an effect on maximal lifespan. Protandim, a mixture of botanical extracts that activate Nrf2, extended median lifespan in males only. Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan. Metformin (0.1%) combined with rapamycin (14 ppm) robustly extended lifespan, suggestive of an added benefit, based on historical comparison with earlier studies of rapamycin given alone. The α-glucosidase inhibitor, acarbose, at a concentration previously tested (1000 ppm), significantly increased median longevity in males and 90th percentile lifespan in both sexes, even when treatment was started at 16 months. Neither fish oil nor UDCA extended lifespan. These results underscore the reproducibility of ITP longevity studies and illustrate the importance of identifying optimal doses in lifespan studies. DOI: 10.1111/acel.12496 PMCID: PMC5013015 PMID: 27312235 [Indexed for MEDLINE] --------- [2] Nat Commun. 2013;4:2192. doi: 10.1038/ncomms3192. Metformin improves healthspan and lifespan in mice. Martin-Montalvo A(1), Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, Gomes AP, Ward TM, Minor RK, Blouin MJ, Schwab M, Pollak M, Zhang Y, Yu Y, Becker KG, Bohr VA, Ingram DK, Sinclair DA, Wolf NS, Spindler SR, Bernier M, de Cabo R. Author information: (1)Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224, USA. Metformin is a drug commonly prescribed to treat patients with type 2 diabetes. Here we show that long-term treatment with metformin (0.1% w/w in diet) starting at middle age extends healthspan and lifespan in male mice, while a higher dose (1% w/w) was toxic. Treatment with metformin mimics some of the benefits of calorie restriction, such as improved physical performance, increased insulin sensitivity, and reduced low-density lipoprotein and cholesterol levels without a decrease in caloric intake. At a molecular level, metformin increases AMP-activated protein kinase activity and increases antioxidant protection, resulting in reductions in both oxidative damage accumulation and chronic inflammation. Our results indicate that these actions may contribute to the beneficial effects of metformin on healthspan and lifespan. These findings are in agreement with current epidemiological data and raise the possibility of metformin-based interventions to promote healthy aging. DOI: 10.1038/ncomms3192 PMCID: PMC3736576 PMID: 23900241 [Indexed for MEDLINE]
  9. Dean Pomerleau

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    Fascinating Tom, Thanks for sharing your thinking on this. I can certainly see the rational for eventually throwing caution to the wind and gambling on a "risky, unproven and speculative treatment" when you've got nothing left to lose. But given your ultraconservative nature and your past vociferous arguments against trusting any results short of personalized medicine, e.g. when you said: I had assumed you'd be one of last to take such a gamble, particularly when the only real evidence for metformin's effectiveness for life extension is in rodents, the applicability of which you've (rightly) long been skeptical about. Was that all talk about high standards of evidence just bluster, to be thrown out when you perceive your prospects as getting desperate? If so, that's good to know. I liked your prison escape analogy, but at the same time it seems pretty facile and self-serving. Given how deliberate and cautious you are, I presume you did a more realistic cost/benefit analysis before starting to take metformin. Would you mind sharing it with us, or reconstructing it? I think it would be a valuable exercise to discuss, since many of us have or will be facing the same sort of decision about whether to gamble on an unproven intervention or continue waiting for more evidence. To illustrate what I have in mind, let me take a stab at it. These are rough, back-of-the-envelope calculations. If you have better numbers or a better approach to a cost benefit analysis, I'd love to hear it. Metformin is believed to be a CR mimetic. As such, it's unlikely to be as effective as the real thing. So I'm going to suppose that if it works, lifelong metformin treatment can extend a rodent's lifespan by 20% (compared with ~40% for lifelong severe CR) relative to ad lib fed rodents. I presume that there is actual data on this, so please feel free to correct me if I'm being pessimistic about metformin's potential for lifespan extension. The evidence suggests that any longevity intervention that targets aspects of metabolism (like CR and metformin) is likely to work significantly less well in long-lived mammals relative to rodents, which are naturally programmed to live fast and die young by default. So metformin in humans is likely to be less effective that in rodents, cutting the 20% lifespan extension down to something closer to 10%. Given you are starting metformin treatment ~2/3rds of the way through your adult lifespan, you're not going to get the full benefit of lifelong metformin, but only ~1/3rd the benefit, cutting the 10% extension down to ~3%. Given you are already practicing mild CR, you are likely already enjoying some of the CR mimetic benefits of metformin. So for you (as opposed to an ad lib eater) the 3% probably gets cut still further, say to ~1-2%. Finally, since you are pulsing metformin in hopes of avoiding potential negative side effects, you likely won't enjoy the full benefits that continuous metformin dosing can potentially offer, further cutting you lifespan benefits to something less than 1%. Human male lifespan is around 80 years. Less than 1% of 80 years is in the neighborhood of six months of extra lifespan. Is this the kind of benefit you are hoping to gain from metformin? If you are hoping for more, can you suggest revisions to my assumptions to justify greater optimism? Do you think such a modest lifespan benefit outweighs the potential risks associated with metformin treatment (including potentially increased dementia risk) in a healthy older person such as yourself? --Dean
  10. Dean Pomerleau

    Metformin linked to higher risk of Alzheimer's and Parkinson's

    Tom, Over here you said: Given your philosophy of "first do no harm", I'm curious what has made you jump on the metformin bandwagon, given previous evidence metformin may interfere with the benefits of exercise and given this new evidence that it may also mess with your brain? As you point out, there isn't any of the high quality evidence of the long term impact of metformin in healthy people that you usually look for. So why are you now inclined to risk taking it given your ultraconservative perspective on supplements, which would seem to extend doubly to outright drugs like metformin? --Dean
  11. Dean Pomerleau

    Finnish study posted by Al Pater

    I stand corrected. You did find one. I'm pretty sure it wouldn't be wise to target a higher cholesterol based on the preponderance of evidence, but who knows. --Dean
  12. Dean Pomerleau

    Finnish study posted by Al Pater

    High cholesterol is positively correlated with longevity late in life. I think you'll have trouble finding a study where mid-life high cholesterol is associated with longer lifespan, as the subjects in this study were. But I'll admit I'm not absolutely sure of this. --Dean
  13. Thanks Karl. I agree that it's disappointing the authors haven't tried the same cocktail in mice to see if it has similar beneficial effects on the thymus and/or epigenetic age, and most importantly, to see if there are any negative side effects of long-term GH treatment that impact longevity. Here is the relevant figure on the Horvath epigenetic age (EA) measures from the Fahy paper: Treatment was conducted in months 0-12, with the 18 month data collected six months after discontinuing treatment on a subset of participants.One thing I noticed from reading the methods section of the full text was that the researchers adjusted the dosage of the elements in the cocktail per individual subject every two months during the study based on blood samples to "maximize IGF‐1 and minimize insulin." Personally I wouldn't be inclined to try to maximizing IGF-1 based on data from rodents and people. --Dean
  14. Dean Pomerleau

    Cronometer results for the FMD

    I take same 100mcg selenium tablets from NOW but only once every 4 days to supplement ~40% of the RDA per day, relying on small amounts from other foods to fill in the rest. --Dean
  15. Dean Pomerleau

    A CR Garden

    Pawpaw Update I'm happy to report my pawpaws have ripened well and they are delicious! Here is a photo of 18 pawpaws, which is about half of my harvest from the single tree that fruited this year (pictured in the top post on this page): You can see the two rows of black seeds running down the middle of the flesh. I'm saving all the seeds. I plan to sprout them over the winter do some "guerrilla planting" in the spring in the woods and open fields near my house. Below is a picture of me holding one for a sense of scale. They are each about 250g (~1/2 pound): At the bottom of the fruit near my palm you can see the divot in the flesh where the fruit was attached to the tree. I'm letting them ripen completely on the tree until they fall off under their own weight. A few of the fruit (5) are still on the tree, as you can see in the photo below. I'm using black crates suspended in the branches under the fruit clusters to catch the fruit when they fall to avoid bruising and prevent animals from taking them! I've eaten a few of the fruit that have already ripened, frozen the pulp from a few and shared a bunch with friends and family. It is about 5-to-1 people who like them vs. people who don't. In fact, my wife was about the only person who really didn't care for them due to both their taste and texture. But she doesn't like either bananas or mangos. She clearly has bad taste :-). They have the smooth custardy texture of durian, for anyone lucky enough to have tried that exotic fruit. As for taste, I'd describe it as a blend of banana and mango or better yet, banana and jackfruit. I really enjoy it. I plan to make vegan pawpaw "ice cream" soon using a combination of frozen pawpaw pulp and frozen bananas. I can't wait! --Dean
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