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Ron Put

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  1. Ron Put

    Jeanne Calment was a fraud?!!

    Tom, your skepticism seems to me a bit too much like a "god is in the gaps" argument. There is enough data at this point to establish some basic probabilities. "Probably" is a key word in life, as well as genetics, period. To give another analogy, If you wear a seat belt and have airbags in your car, your chances of surviving a crash generally increase compared to someone who does not. But there are specific instances where these safety measures may not work, and even be detrimental. For instance, under very specific circumstances, people of slight stature, may even receive more damage by such safety devices than from a particular crash. If I understand your absolutist argument, you should be waiting until we have "smart" materials and safety devices which adapt to an individual's physical characteristics AND the conditions. AND have absolutely no error rate.... And yet, you appear to throw your skepticism out of the window the moment you are presented with a PR blurb touting an "app that makes it easy for everyone to understand the right foods for their unique metabolism in order to improve long-term health and manage weight more easily." Or, the moment you see a BBC headline proclaiming that a quarter of a million CENTENARIANS have gone missing in Japan.... 😄
  2. Ron Put

    Jeanne Calment was a fraud?!!

    Looking at the Promethease description for rs4977574, it states: "Some studies - but not others - report a slightly increased risk for myocardial infarction." While this points to an interesting aberration, replacing vegetables with bacon and drinking a bottle of wine a day is probably not a wise decision for anyone, based on preponderance of all available evidence. Humans are made up of more than rs4977574 and my guess is that other factors may be at play as well. Here is something else to ponder: "RESULTS: There were 925 cases with CAD and 634 without CAD enrolled in the present study. The G allele conferred a significant increase in risk of CAD (odds ratio = 1.47, P = 0.003 in the dominant model; odds ratio = 1.36, P = 0.018 in the recessive model). During a median of 11 years (inter-quartile range between 5.2 and 12.5 years) of follow-up, neither the total nor the cardiovascular mortality was different among CAD subjects with different genotypes. Using Cox regression analysis, genotypes of rs4977574 still failed to predict cardiovascular mortality (hazard ratio = 1.25, P = 0.138 in the dominant model; hazard ratio = 1.05, P = 0.729 in the recessive model). CONCLUSIONS: The rs4977574 at chromosome 9p21 is associated with presence of CAD in Han Chinese. However, rs4977574 could not predict cardiovascular mortality in these CAD subjects during the eleven-year period of the study." https://www.ncbi.nlm.nih.gov/pubmed/24804228?dopt=Abstract
  3. Good points and data, mccoy. I am still unsure I grasp the data, or at least am not entirely comfortable with what I am grasping from the data. Part of it may be my confusion of what constitutes "high" levels in a lot of the studies (apart from the Longo studies). From what I read, it would appear that higher IGF-1 levels are beneficial, up to close to 200 ng/ml, as long as one does not have cancer. If cancer is present, then IGF-1 is detrimental. Yet other studies find no relation between IGF-1 and longevity, unless too low or too high. Even looking at the levels in Fig. 2 above, the A/A homozygous subjects show about 200 ng/ml on average at the age of 75-85, which is actually rather high for that age (kind of like Okinawans having higher levels of testosterone than the general population). Again, this is likely my own confirmation bias talking, but the questions it rises are still valid, I think.
  4. Ron Put

    Jeanne Calment was a fraud?!!

    Tom, I am not sure that I agree with your strongly worded conclusions, based on what I read from your link. This large variation is only partly explained by genetic factors (less than 50% for glucose, less than 30% for insulin and less than 20% for triglycerides) and there is only a weak correlation between an individual's responses to fat and carbohydrates. Identical twins who share all their genes and most of their environment often had different responses to identical foods. The study also finds that identical twins shared just 37% of their gut microbes - only slightly higher than the 35% shared between two unrelated individuals. ... The results suggest that personal differences in metabolism due to factors such as the gut microbiome, meal timing and exercise are just as important as the nutritional composition of foods, supporting the idea that simple nutritional labeling is insufficient for assessing food. This actually seems to support the notion that there are some general guidelines which apply to human populations regardless of specific genetic attributes. If you eat, for example, a (healthy) vegan diet, your microbiome will fit a certain pattern and if you eat lots of meat and dairy, your microbiome will fit a different broad pattern. In other words, catering to your current microbiome may, or may not be "optimum" for you, whatever that means. Moreover, your microbiome will dramatically and usually rather rapidly change, based on changes in your diet and lifestyle, too, as seen by testing through companies like uBiome. Why would one need to show "identical health outcomes in any two individuals?!!" We are talking probabilities and patterns. To use the smoking argument, one may get lung cancer without ever having smoked and some life-long smokers do not get lung cancer. But it doesn't mean that smoking tobacco does not significantly increase the likelihood of developing a p53 mutation which leads to cancer. What does this even mean? We already know what diets broadly improve the healthspan of populations -- we just can't make most people to follow them. What makes you think that if a "truly optimal diet tailored to the particular individual" (whatever this means to you) was possible to design, that individual would follow it, any more than they follow the general broad guidelines? And, finally, speaking of BS meters, this is quite notable: "About ZOE: ZOE is a nutritional science company on a mission to help people eat with confidence. We are leading the world's largest ongoing scientific nutritional research project to understand our unique responses to food, developing a consumer at-home test and app that makes it easy for everyone to understand the right foods for their unique metabolism in order to improve long-term health and manage weight more easily." It reminds me of one of popular "blood type diet" apps which had a tagline going something like: "Everybody is different! Ever body is different! Personalized nutrition for everybody!" 😄
  5. Ron Put

    Jeanne Calment was a fraud?!!

    Actually, all that's needed for you to be wrong is to show broad correlations which can be tested by their broad predictive power. And this is exactly how we know that certain habits are healthier than others and certain habits are worse than others. Such reasoning is easy to be exploited and it often is. The anti-vaxers fall into this category. But probably the most glaring example is the case with tobacco smoking and its correlation with increased mortality, which had been noted as early as the 17th century in Europe. But tobacco companies were able to seed enough doubt to exploit the confirmation bias of smokers and would be smokers and make them ignore the broad evidence. Exceptions such as the odd old geezer who smoked (including Calment, who actually smoked one cigarette on most days) were touted to make the point of each one's "uniqueness." Even after the exact effect of tobacco smoking on the mutation process of the p53 gene was shown in the 1990s, there is enough random nonsense floating around the web touting uniqueness and the very real ability of some individuals to resist such mutations. But the fact is, for the vast majority of humans, smoking is bad. Just like for the vast majority of humans, eating more fruits and vegetables is much better than eating a lot of sausages, steaks and buckets of KFC. As to microbiomes, yes, they are different. But if you look at the data provided by uBiome, for instance, you'll find broad similarities between vegans and vegetarians, and obese meat-eaters. You can choose to ignore it, because you convince yourself that the probabilities do not apply to you, but the science behind it remains valid, nevertheless. As to this Russian-driven Calment conspiracy theory, it has all the credibility of Pizza-gate. But there were lots of folks who believed in that, too.
  6. mccoy, I think the issue with the scatterplot in that particular figure is that the relationship they are describing is not linear, so r=0.18 is misleading in this context. Note this statement: "age-related increase in the A-allele of rs2229765 and a change in the plasma level of IGF-1, which dropped significantly after 85 years of age (85+ group). In the male 85+ group, A/A homozygous subjects had the lowest plasma IGF-1 level." Then look at the A/As in this figure and their plasma IGF-1 at 70-85 and then at 85+, compared to G/G and G/A:
  7. Thanks for the great summary, Sibiriak. I am still confused though, because they effectively say that there is no correlation between longevity in humans and total IGF-1 or IGF-1/IGFBP-3 ratio, only with IGF-1 bioactivity. The study I cited above also appears to indicate higher IFG-1 being beneficial until about 85 and then lower IFG-1 being beneficial to survival. See also this one: "It’s not quite the elixir of life, but researchers have at last identified gene variants that make people live longer. Men may miss out, as all carriers identified so far are women. They are also slightly shorter than average. ... Both mutations affect the receptor for insulin-like growth factor 1 (IGF1), a driver of bodily growth and maturity, especially during puberty. By making the receptor slightly faulty, the mutations may disrupt IGF1 binding and decelerate the process of maturation and ageing. In support, they found circulating levels of IGF1 to be 37% higher in carriers of the mutation, probably to compensate for the underperforming receptor. Carriers were also 2.5 centimetres shorter on average than the general population. ..." https://www.newscientist.com/article/dn13403-long-life-genes-found-in-100-year-old-humans/ I am debating if I should dramatically reduce my (plant) protein intake (currently at about 1.4g per kg), since my IGF-1 is now above 180. My guess is this will adversely affect muscle mass, which is also an issue. And then I look at the human studies about IGF-1 and am starting to think that maybe I shouldn't worry so much about IGF-1 levels (confirmation bias may also play a role in my case) 🙂
  8. And to make the whole IGF-1 thing more confusing, an older article: "Elderly men with higher activity of the hormone IGF-1--or insulin-growth factor 1--appear to have greater life expectancy and reduced cardiovascular risk, according to a new study. IGF-1 is a hormone similar in molecular structure to insulin. It is released from the liver and plays an important role in childhood growth and continues to have anabolic effects in adults. In this study, researchers evaluated 376 healthy elderly men between the ages of 73 and 94 years. A serum sample was taken from each subject at the beginning of the study and researchers were contacted about the status of the participants over a period of eight years. Subjects with the lowest IGF-1 function had a significantly higher mortality rate than subjects with the highest IGF-1 bioactivity. These results were especially significant in individuals who have a high risk to die from cardiovascular complications. These new findings come as a result of a new form of testing for IGF-bioactivity. Researchers in this study used a new method, a bioassay, to measure the function of IGF-1 in the blood. Compared to commonly used methods to measure IGF-1, the IGF-1 bioassay gives more information about the actual function (bioactivity) of circulating IGF-1 in the body. "The bioassay allowed us to more clearly see the association between high circulating IGF-1 bioactivity and extended survival," said Michael Brugts, MD, of the Erasmus Medical Center in Rotterdam, The Netherlands and lead author of the study. "Interestingly, we could not find such a relationship when IGF-1 in blood was measured with the more commonly used methods." Immunoassays, commonly used previously to determine IGF-1 circulation levels, remove certain proteins that interfere with accurate measurements. Recent studies however have found that these proteins are important modulators of IGF-1 bioactivity. The bioassay used in this study does not disregard or remove this protein, thus enabling researchers to have a more accurate understanding of IGF-1 function. ..." https://www.sciencedaily.com/releases/2008/05/080527084252.htm
  9. Ron Put

    TMAO & Cardiovascular Disease

    Thanks, Sibiriak. Very informative and rather convincing, to me at least. I've reduced my Alpha CPG dose to 150 (from 300 over the past six months or so), but will continue taking it, since by my count, there are plenty of days I don't hit 400.
  10. Well, if one does a little research, its predictive abilities are rather good and better than most. It also jives with other research on the subject (e.g., https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12557 ) As to increased MCV values, as I noted above, the key is being asymptomatic (although I ran into a study I'll cite below which seems to indicate otherwise). For instance, during fasting, MCV values generally increase, as folate, B-12 and iron are depleted. Chronic deficiencies in those would also trigger an increase in MCV. Rapid turnover of RBCs will also do it. RBCs also depend on glucose for survival, so very low glucose levels would impact them as well (not so in my case). Or B malabsorbtion. In my case, I was thinking of double checking my B-12, since my folate appears fine. But it also appears rather well documented that increased MCV are predictive of mortality in many clinical instances. Here are a couple of examples: The prognostic value of interaction between mean corpuscular volume and red cell distribution width in mortality in chronic kidney disease Mean corpuscular volume levels and all-cause and liver cancer mortality "Elevated MCV level was related to an increased risk of liver cancer mortality in men (aHR, 3.55; 95% CI, 1.75-7.21). Conclusions: This study suggests that the elevated MCV level in non-anemic cancer-free individuals was associated with increased all-cause mortality in both men and women, and with cancer mortality, in particular liver cancer mortality in men."
  11. There may be an interesting genetic component to IGF-1 levels, too, at least among men, which facilitates speedier decline in IGF-1 after about the age of 85 and thus promotes longevity (as long as they make it there): "Males showed an age-related increase in the A-allele of rs2229765 and a change in the plasma level of IGF-1, which dropped significantly after 85 years of age (85+ group). In the male 85+ group, A/A homozygous subjects had the lowest plasma IGF-1 level. We found no clear correlation between rs2229765 genotype and IGF-1 in the females. Conclusion These findings confirm the importance of the rs2229765 minor allele as a genetic predisposing factor for longevity in Italy where a sex-specific pattern for IGF-1 attenuation with ageing was found." https://bmcgeriatr.biomedcentral.com/articles/10.1186/1471-2318-9-19
  12. Interesting. They mention age-related narrowing of blood vessels as possible part of the mechanism. I'd guess that CR and low, plant based protein diet, may help ameliorate such effect.
  13. Yeah, my MCV has gone up to just over 100, but it seems that if asymptomatic, elevated MCV is not an issue. You look younger than that 😄 😄 It looks like RDW has a large effect. Also CRP. I am 42.49 for phenotypic and 42.04 for DNAm age. I really wanted to be in my 30s.... 😄
  14. So, after running close to 1:1 ration of Omega-3 to Omega-6, I noticed some significant changes: Cholesterol: 153 LDL: 72 HDL: 71 Triglycerides: 51 My testosterone has gone up a bit, to just over 900 ng/dL Interestingly, my IGF-1 has also gone up to over 180 ng/mL, although my insulin is pretty low at 2.5 uIU/mL, with glucose at 83. My protein intake (all plant) is 1.39g per kg, which is kind of high, I guess, but I don't know if I can drop it significantly and still stay all green for all the nutrients in Cronometer. Today Withings has me at 64.2kg, 18.7 BMI, 9.6% body fat and 85.8% muscle mass. I am a vegetarian, almost vegan, so my Omega 3 comes from stuff like flax, chia, legumes, walnuts and greens. Almost no olive oil (maybe 3-4 times a month, about 2 tbsp at a time or so). I do take olive leaf powder almost every day. So, the big change is the drop in total cholesterol. I wonder what's with the IGF-1, but I am happy with my numbers overall and will likely keep the the 1:1 Omega 3 to Omega 6 ratio going forward.
  15. Wow.... Nobody here was interested enough to run their numbers? It seems to be the most accurate of the phenotypic age and mortality predictors I've come across.
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