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  1. [Admin Note: This is a series of posts originally on another thread that started on the topic of how cold exposure can have beneficial effects for health and longevity despite increasing calorie expenditure. I debated where to move them, since they seem to fit General Health & Longevity, CR Practice, and CR Science. I finally opted for CR Science, since you'll see if you haven't been reading them already, they bear directly on CR and CR mimetics. If anyone feels strongly this was the wrong choice, I'll be happy to move the thread to another forum. --Dean] Rodney, Whenever I see someone use the word "surely", I figure the writer isn't very sure about, or doesn't have real evidence to support, what they are about to say. I'm guilty of it sometimes myself. People's appetites differ for a lot of reasons, many of them without negative health implications. Genetics is one example that can alter metabolic rate and therefore hunger (remember the ob/ob mice who ate more but didn't live shorter lives). Exercise or exposure to cold (and extra brown fat that cold exposure can create/promote) will increase calorie expenditure without detrimental effects. In fact, perhaps my favorite study of all time (except for the suffering of the animals involved) was the famous "rats with cold feet" study [1] by John Holloszy. Holloszy found that rats who lived their lives standing in a cold puddle of water ate 44% more than normally-housed rats, but nonetheless stayed thin and didn't live any shorter lives than the normally-housed rats. In fact they lived slightly longer and got less cancer. Our friend Josh Mitteldorf did a whole blog post about the hormetic benefits of cold exposure, and how it casts serious doubt (if not debunks) the popular "rate of living" theory of aging. --Dean (who composed this post while pedalling shirtless and wearing just bike shorts on his stationary bike in his 59 degF basement to maximize hormesis... ) -------- [1] J Appl Physiol (1985). 1986 Nov;61(5):1656-60. Longevity of cold-exposed rats: a reevaluation of the "rate-of-living theory". Holloszy JO, Smith EK. It has been postulated that increased energy expenditure results in shortened survival. To test this "rate-of-living theory" we examined the effect of raising energy expenditure by means of cold exposure on the longevity of rats. Male 6-mo-old SPF Long-Evans rats were gradually accustomed to immersion in cool water (23 degrees C). After 3 mo they were standing in the cool water for 4 h/day, 5 days/wk. They were maintained on this program until age 32 mo. The cold exposure resulted in a 44% increase in food intake (P less than 0.001). Despite their greater food intake, the cold-exposed rats' body weights were significantly lower than those of control animals from age 11 to 32 mo. The average age at death of the cold-exposed rats was 968 +/- 141 days compared with 923 +/- 159 days for the controls. The cold exposure appeared to protect against neoplasia, particularly sarcomas; only 24% of the necropsied cold-exposed rats had malignancies compared with 57% for the controls. The results of this study provide no support for the concept that increased energy expenditure decreases longevity. PMID: 3781978 [PubMed - indexed for MEDLINE]
  2. The email list system is broken. Posts cannot be searched. Many of the posts do not make it to the messages I receive individually and via the daily mailings. Therefore, I am sending this message, comprised of citations papers that seem to be appropriate to the room of the Forum. I will try to also provide full-text links and a very brief excerpt or within brackets my synopsis of the paper. I apologize for the fact some papers discuss results of studies on the overweight or obese, but feel that some benefits seen in such subjects bears on a continuum of benefits accrued by CR and provide incentive to folks who are overweight or obese. Below are today's papers. Altered consolidation of extinction-like inhibitory learning in genotype-specific dysfunctional coping fostered by chronic stress in mice. Campus P, Maiolati M, Orsini C, Cabib S. Behav Brain Res. 2016 Aug 6. pii: S0166-4328(16)30505-8. doi: 10.1016/j.bbr.2016.08.014. [Epub ahead of print] PMID: 27506654 http://linkinghub.elsevier.com.sci-hub.cc/retrieve/pii/S0166432816305058 These findings support the conclusion that an experience of reduced food availability strain-specifically affects persistence of newly acquired passive coping strategies by altering consolidation of extinction-like inhibitory learning. The interaction of fasting, caloric restriction, and diet-induced obesity with 17β-estradiol on the expression of KNDy neuropeptides and their receptors in the female mouse. Yang JA, Yasrebi A, Snyder M, Roepke TA. Mol Cell Endocrinol. 2016 Aug 6. pii: S0303-7207(16)30298-2. doi: 10.1016/j.mce.2016.08.008. [Epub ahead of print] PMID: 27507595 http://linkinghub.elsevier.com.sci-hub.cc/retrieve/pii/S0303720716302982 [This paper suggests that steroidal environment and energy state negatively regulate KNDy (Kisspeptin/Neurokinin B/Dynorphin) gene which plays an important role in the https://en.wikipedia.org/wiki/Hypothalamic%E2%80%93pituitary%E2%80%93gonadal_axis] Effects of dietary supplementation with EPA and/or α-lipoic acid on adipose tissue transcriptomic profile of healthy overweight/obese women following a hypocaloric diet. Huerta AE, Prieto-Hontoria PL, Fernández-Galilea M, Escoté X, Martínez JA, Moreno-Aliaga MJ. Biofactors. 2016 Aug 10. doi: 10.1002/biof.1317. [Epub ahead of print] PMID: 27507611 http://sci-hub.cc/doi/10.1002/biof.1317 α-lipoic acid, especially in combination with EPA, upregulated the expression of genes associated with lipid catabolism while downregulated genes involved in lipids storage. Association of the TNF-alpha -308 G/A polymorphisms with metabolic responses secondary to a high protein/low carbohydrate versus a standard hypocaloric diet. De Luis DA, Aller R, Izaola O, Romero E. Nutr Hosp. 2016 Jun 30;33(3):267. doi: 10.20960/nh.267. Spanish. PMID: 27513494 [i have no access to this paper's full texts.] Carriers of -308 GG promoter variant of TNF-alpha gene have a better metabolic response than -308 GA obese with a high protein hypocaloric diet.
  3. My detailed write-up on science of fasting. Please check it out and let me know any comments. https://spyderdoc.substack.com/p/doctors-heart-series-part-6-science Thanks, Suman Manchireddy MD
  4. Hi CR Society Friends! For my first post here, I'd like to ask our community if anyone has come across published research similar to that which is currently being discussed in the "Fasting for CR Benefits?" topic in this forum. That topic, which I highly recommend, is discussing the University of Wisconsin-Madison study on fasting driving the positive effects of a CR diet in mice. So as to not sidetrack that topic, anyone familiar with studies that, for example, have compared time restricted feeding (TRF) windows (16:8 versus 18:6?), particularly in relation to CR, is more than welcome to discuss them here. One study (Sutton et al., 2018) randomized men with prediabetes into an early TRF (6 hour feeding period, with dinner before 3 p.m.) or a control schedule (12 hour feeding period) and later crossed the groups over to the other schedule. The early TRF significantly improved some aspects of cardiometabolic health (even without any weight loss). My criticism of that study is that there were two (potentially confounding) variables (early versus later eating as well as a 6 versus 12 hour feeding window) that differed in the experimental and control groups. The study begs for a follow-up (which I haven't found) comparing only early versus late TRF. Nonetheless, the results are noteworthy. I'd very much appreciate reading anyone's thoughts or knowledge on such topics. Thanks!
  5. I have embarked upon a quest to lengthen my telomeres. Intermittent Fasting is one technique I am utilizing in my effort. The type of Intermittent Fasting I am practicing is water fasts on Tuesdays and Thursdays. Has anyone had their telomeres measured? Does anyone have any input and/or suggestions regarding my objective?
  6. The strategies are pretty standard but still pretty interesting for anyone who’s looked into ‘biohacking’. The guy is a CEO of a company that does half a billion dollars a year in revenue so he definitely has to be high performing. Funny enough he follows a ketogenic diet, fasts frequently and uses ssri’s for mood improvement. Here’s his whole protocol: https://hackernoon.com/im-32-and-spent-200k-on-biohacking-became-calmer-thinner-extroverted-healthier-happier-2a2e846ae113
  7. Valter Longo's work has been discussed around here quite frequently as of late, particularly his work on the fasting mimicking diet. In typical Rich Roll fashion, he goes long form and tries to gain deep insight into Longo's understanding of nutrition, longevity, and health. Rich says that he considers it one of his most important conversations to date.
  8. Sorry everyone. It appears Valter Longo has patented intermittent fasting. So you all gotta pay up. Seriously. Pretty crazy. Here is the abstract from the patent, which was just granted last month: Methods and diets for lowering glucose and/or IGF-1 levels US 9237761 B2 ABSTRACT A method of improving longevity and/or alleviating a symptom of aging or preventing age related diseases is provided. The method includes a step in which the subject's average and type of daily protein intake, IGF-I, and IGFBP1 levels, and risk factors for overall mortality, cancer and diabetes are determined. With respect to protein consumption, the relative amounts of protein calories from animal and plant sources are determined. A periodic normal calorie or low calorie but low protein fasting mimicking diet with frequencies of every 2 weeks to 2 months is provided to the subject if the subject's average daily protein intake level and type and/or IGF-I levels, and/or IGFBP1 levels is identified as being greater or lower than a predetermined cutoff intake/level and if the subject is younger than a predetermined age. The method is also shown to alleviate symptoms of chemotoxicity. I'm no patent attorney, but it would seem like there should be sufficient "prior art" to invalidate this patent. --Dean
  9. I'm sure this movie will be of interest to many CR members. I just watched it and thought it was an interesting film that included the pros/cons of fasting. The movie talks about many different forms of fasting (IF, TRF, multi-day water fasts, juice fasts, etc.). It includes appearances from many big names including Valter Longo, Alan Goldhammer, and many more. Before I muddy the waters and give my thoughts, I would be curious as to what others think. The cost to rent it is relatively inexpensive. The movie can be viewed here: http://fastingmovie.com/
  10. Hi everyone, Many people have been asking, both here and elsewhere, about the safety and efficacy of various time-restricted eating schemes. This is of particular interest to me since, for reasons that are irrelevant to most here (an unusual constellation of health challenges), I have been finding conventional CR (=the same, low energy intake per day) unworkable. Before I continue, I should emphasize that the best bet for health and longevity, based on the science we have (which is limited), is indeed conventional CR. But for those who want to try time-restricted eating, I'm wondering about the relative merits of two approaches, and I'd appreciate feedback. I've been thinking this through mostly on my own, and find myself unable to reach a conclusion. Experimental evidence is so limited, I think it's more helpful to reflect a bit on mechanisms, or even evolution. (More helpful doesn't mean very helpful, though....) Type 1: Longo/FMD. The evidence for benefit in both lab animals and humans is limited, but is at least somewhat compelling. It seems unlikely that there's any antiaging benefit per se, beyond that which would have obtained with the same overall ("longish-period averaged") reduction in calories. Type 2: "Inverted FMD". If the Longo approach involves having non-CR signaling patterns (high mTOR, IGF1, insulin, etc.) be the norm, with a sudden several-day period of CR signaling patterns being the exception, "inverted FMD" would be CR, perhaps somewhat mild, as the norm, with a several-day, or week-long period of "feast" signaling. (Credit where credit is due: James Clement is the one who suggested this pattern of eating as possibly better than the Longo pattern.) Type 1 vs. Type 2. Type 2 seems to me to be more like the pattern of eating under which we evolved – scarcity as the norm, with the occasional feast when the tribe came upon a bunch of food – but that doesn't say much about its benefits, though it might suggest that the body would be more adapted to it. Hm.... what we really need is more science on this. Does anyone here know Longo? I've emailed him a couple times and not gotten a response. A small trial comparing the two approaches could be helpful (though only slightly of course, since the main interest of many here is effect on mortality, for which we still don't have great biomarkers). Brian
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