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About mccoy

  • Birthday 01/01/1960

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  1. Front Endocrinol (Lausanne). 2019; 10: 27. Published online 2019 Feb 1. doi: 10.3389/fendo.2019.00027 PMCID: PMC6367275 PMID: 30774624 ROLE of IGF-1 System in the Modulation of Longevity: Controversies and New Insights From a Centenarians' Perspective Giovanni Vitale,1,2,* Giuseppe Pellegrino,3 Maria Vollery,4 and Leo J. Hofland5 Author information Article notes Copyright and License information Disclaimer Go to: Abstract Human aging is currently defined as a physiological decline of biological functions in the body with a continual adaptation to internal and external damaging. The endocrine system plays a major role in orchestrating cellular interactions, metabolism, growth, and aging. Several in vivo studies from worms to mice showed that downregulated activity of the GH/IGF-1/insulin pathway could be beneficial for the extension of human life span, whereas results are contradictory in humans. In the present review, we discuss the potential role of the IGF-1 system in modulation of longevity, hypothesizing that the endocrine and metabolic adaptation observed in centenarians and in mammals during caloric restriction may be a physiological strategy for extending lifespan through a slower cell growing/metabolism, a better physiologic reserve capacity, a shift of cellular metabolism from cell proliferation to repair activities and a decrease in accumulation of senescent cells. Therefore, understanding of the link between IGF-1/insulin system and longevity may have future clinical applications in promoting healthy aging and in Rehabilitation Medicine.
  2. Ron, I could not read the full article by Burgers et al. since presently sci-hub is not reachable from here. Judging by the plots only, even at 150 ng/ml the hazard ratio is pretty high for cancer, whereas it's zero for CVD. I must confess the scale on the Y axis makes me wonder, it reads log hazard ratio but there is a zero and negative numbers which clashes with the definition of logarithms. So I dont't know the exact parameter and if there is some tricky scale effects which amplifies the vertical scale. Higher IGF-1 is ostensibly beneficial to the nervous system and skeletal muscle-system, but I know no literature about that. Very regular exercise according to Longo may substitute higher IGF-1 to boost muscle protein synthesis and avoid sarcopenia. In such a way it would be possible not to increase protein when over 65. In theory, at least. Obviously, familiarity with cancer or previous cancers would suggest strongly to try and do whatever is possible to keep IGF-1 at the optimum range of 100-120 mg/ml, if it is possible at all to manage IGF-1 in such an accurate fashion (probably not). Also, if familiarity or previous cancers are present, it makes sense to adopt a more accurate risk level analyzing IGFBP and free IGF-1, if we have data, benchmarks, optimum ranges about them to guide us in a preventional scheme. Further confounding factors may be IGF-1 receptor sensitivity and activation of the post-receptor pathway. An optimum plasma IGF-1 may turn out to result in high IGF-1 signaling effects (for example in the mTOR pathway) in the presence of high receptor sensitivity and the other way around Maybe I'll have to listen again to the Peter Attia podcast with Barzilai, where they discuss IGF-1 and longevity. I remember Barzilai said that the lower IGF-1 in some more longeve people may be reverse causation (they are not more longeve because of the low IGF-1 but they are approaching death and the drop in IGF-1 is a consequence of that)
  3. mccoy

    Jeanne Calment was a fraud?!!

    Right, thanks for reminding. Also, one point that pretty much baffled me (discussed in the exercise and blood glucose thread) is that it appears that it isn't so easy to lower post prandial glucose peaks, even with exercise . So the advantage of wanting to lower BG with its peaks at all costs may be dubious (too much time and energies required and a choice of foods which is not undisputably healthier). It remains pretty controversial as a topic though. I'd like to underline that I'm eating plenty carbs right now, simple and complex but I'm ready to intervene should my fasting BG cross consistently the prediabetic borderline (100 mg/dl).
  4. According to the above metanalysis by Burgers et al., 2011, Low levels of IGF-1 are bad for either CVD risk and cancer risk. High levels are bad for cancer risk. My doubt is that the optimum range for minimum cancer risk seems to be pretty narrow, let's say in the 100-125 ng/ml interval. Keeping the IGF-1 constantly within this range would probably be very hard. Also, the whole range stands below Longo's optimum value of 140 ng/ml- The takehome lesson is pretty clear though. CR practitioners should check that IGF-1 is not too low, resulting in increased all causes mortality. Conversely, non CR practitioners should check that it is not too high. Dr. Fuhrman's 100-150 optimum range seems to be relatively accurate but maybe too excessive in the higher end of the interval , according always to the Burgers et al. metanalysis.
  5. These are the podcast notes in the PA-Rhonda epipsode. Some optimum values for IGF-1 are displayed. source: J Clin Endocrinol Metab. 2011 Sep;96(9):2912-20. doi: 10.1210/jc.2011-1377. Epub 2011 Jul 27. Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality.
  6. Ron, I agree, the genotype A/A exhibits the lowest IGF-1 range in males with age > 85, whereas other genotypes do not exhibit such a drop, so maybe study of the A/A genotype in males > 85 years might be of relevance to longevity. Not a big takehome lesson, nothing immediately applicable by ourselves methinks. And back to the IGF-1 plot, I really don't see any correlation even in the non linear fashion. Besides, the values are so scattered and there are such montruos outliers that no practical conclusions can be reached. I believe so far the only scheme we could agree upon is to take as a reference Valter Longo's 140 ng/mL, check our values, try to comply by adjusting our protein and especially methionine intake. If the values are pretty far from Longo's optimum, then there might be some particular issue to figure out.
  7. mccoy

    Jeanne Calment was a fraud?!!

    AFAIK the ZOE project is similar to the Israelian project of monitoring individual blood glucose by continuos glucometer in response to various food and meals. The studies by Elinav and Segal, which we previously discussed in this forum, according to which the blood glucose response after the ingestion of the same foods varies wildly across individuals. Teh authors wrote a book on the project (The personalized diet) plus at least an article discussed in this same forum. The results seem to support the value of individual nutrition to optimize blood glucose, admittedly in a pretty costly fashion (cost of glucometer about 1500 US$ plus 500 US$ per month for the dermic sensor) or in a pretty unconvenient way (multiple pricks and monitoring by common portable glucometers).
  8. TAt a first reading the article was not very clear, so I'll have to delve deeper into it. The following plot though shows extremely scattered values of IGF-1 with age and the correlation coefficient is close to zero. (r=-0.18). In the technical fields, such a coefficient would suggest no correlation at all. I really do not understand how the basic assumption of a study can be based on such scattered and almost uncorrelated data.
  9. mccoy

    Cholesterol paradox

    Back to cholesterol with more data in my head. All right, I understood at last that cholesterol is synthetized by cells and that dislypidemia is a problem of faulty homeostasis even though often wrong dietary habits may be a cofactor. When the paleo say that we need to ingest cholesterol which is fundamental to life, they ignore that the body is very well capable to provide for himself. In Peter attia's series on lipidology with Tom Daysprings, statins are discussed with unusual detail, a suggested listening to those who are taking them.
  10. Today while walking in shorts under a powerful midday sun I listened to this podcast. (The above was an optimization of an hour of spare time: mild post-meal exercise+UV rays absorption+ listening to useful content). The series is not very well known but the interview was pretty clarificatory of quite a few concepts which are not utterly limpid in his book. The host is an MD + former crossfit athlete. Longo speaks about the 5 pillars, dieting and keto diets, why a pescetarian diet, exercise and a few other details. He confirms a 60-30-10 ideal in his opinion C-F-P ratio with an isocaloric regimen. Longo remains the very first benchmark in longevity to whom I would address all those who ask for a reference. I do not follow all his suggestions but IMHO he remains probably the most formidable source for longevity suggestions.
  11. mccoy

    Cronometer results for the FMD

    Another potential problem causing condition cited by Longo is an inefficient hepatic gluconeogenesis, due to genetic polymorphisms. It may cause hypoglicemia and fainting, maybe it was the cause of frequent finting in a 5-days water fast reported by a user in this board. The frequency of occurrance is not cited though.
  12. mccoy

    Allulose - any takers?

    Hi listened to that episode of Peter Attia's podcast, but really didn't remember about allulose. I then discovered that it's not allowed in Europe and, as a matter of fact, it's not sold by the domestic Amazon organization. It sounds promising though. Presently I consume stevia and erytritol, when I do not consume dark honey, my favourite sweetener. An issue with stevia and low-calories saweeteners is that they must be used sparingly adn dosed exactly, lest the taste becomes horribly sweet and cloying, in such cases I prefer to throw the food away. Also, not every food is compatible with stevia's aftertaste, although I must confess that Truvia (stevia + erythritol) tastes pretty good as a whole.
  13. mccoy

    Remember the precautionary principal

    The fact that they invited Valter Longo in one of their episodes belies a degree of objectivity. Also, the host did not insist too much questioning Longo on an issue of meat consumtion.
  14. mccoy

    Medicine focused podcasts

    Of course, CM has his personal ideas on optimal nutrition (he supports the consumption of organ meats) but across the board is pretty objective and encompasses in his suggestion vegan and vegetarian regimens. Re: choline, Masterjohn gives quite a few alternatives if I'm not wrong, like improve the methylation requirements or consume TMG/betaine. Last time I had a blood check my homocysteine was high, so I'm curious if all the countermeasures I undertook were effective. Back to the podcast, I've started listening to the nutrition in neuroscience series a second time. Pretty deep and pretty heavy as well. Probably best digested in small meals!