Talk:Caloric restriction mimetic

Untitled
All:

I recently added the term "cr mimetic" to Wiki, later to find it removed due to copyright issues:

"Text that was previously posted here is the same as the text from the source below:

http://www.cron-web.org/cr-mimetics.html "

I own that domain. The content on that site is original except that which is in quotes or properly footnote-referenced. I am also one of the original officers of The Calorie Restriction (CR) Society (www.calorierestriction.org), the only organization devoted to human CR.

You may do a standard Google search for me, "Khurram Hashmi" and "Calorie Restriction" for references.

Thank You, Khurram Hashmi -- calorierestriction.org CRON-WEB.org

Title
The title of the page should read "C.R. mimetic", not "Cr mimetic". Ideally, it should be spelled out: "Caloric Restriction Mimetic". Unfortunately, I don't know how to change the title of a page, so I leave it to those more knowlegeable than I to do so. Lorangriel 20:59, 3 April 2007 (UTC)

Cannabanoid Antagonists
These aren't true C.R. mimetics. They are appetite inhibitors, and I don't think they belong in this article. Debate? RGK (talk) 09:22, 5 October 2009 (UTC)

Inviting Comments and Debate before Endeavoring to Significantly Expand/Edit this Article
I've been working on a paper with working title of either: (1) ''How the Future of Medicine is Linked to Our History of Famine: Plant Polyphenols As Epigenetic Activators for Calorie Restriction Mimetics, or (2) Why Bacteria Laden, Moldy, Fungi Infected Food Crops will Probably Prevent Cardiovascular Disease, Prevent Cancer from Spreading, Make Your Skin Beautiful, Prevent Metabolic Syndrome and Diabides Type 2, Slow Down the Aging Process and Extend Your Life. (Assuming it Doesn't Almost Immediately Kill You First.) '' 71.105.250.25 (talk) 09:06, 5 October 2009 (UTC) But, seriously. I'm developing quite a database of articles and knowledge on this subject; however, I've published/modified articles before (unilaterally) and didn't really enjoy the time-consuming, post editing debates that followed. (See Afd SOD/CAT) So, this time I'd like to reach a consensus--of at least greater than one--before I'd personally alter anything in the existing article. Whose with me? I say we keep all the comments on this discussion page for convenience. Anyone whose ever done any creative brainstorming knows that the initial process should non-judgmentally evaluate any reasonable hypothesis related to the subject matter. I would like to see a discussion evolve that promoted a broad range of insights into this subject matter, and I would hope that participants would reserve judgment so as not to stifle the initial brainstorming process. RGK (talk) 09:45, 5 October 2009 (UTC)

71.105.250.25 (talk) 09:06, 5 October 2009 (UTC)

Sirtris Pharmaceutical
The sirtuin drug candidates under development at Sirtris warrant an extensive discussion here. The fact that GlaxoSmithKline paid $720 million a few months ago for this company is a very strong endorsement for the future of this technology for medicine.

C.R. Mimetics: Medicine or Missing Non-Nutritive, Essential Cell Signalling Componets
I've been working with these phytochemicals for twenty-five years. Anecdotally, I see dramatic effects on humans and companion animals by the restoration of one or more of these calorie restriction mimetic compounds to the diet. I believe that there are many, many C.R. mimetic polyphenol compounds in unprocessed foods when their symbiotic (non-pathogenic) soil bacterium are allowed to remain a component of the food crops. However, the economic reality is that it is far cheaper to sterilize or nearly sterilize a raw grain or fresh vegetable food crop, than it would be to perform multiple, specialized tests for specific pathogens. Modern food processing techiques started with Pastuer's work eliminating pathogens from milk, and in the aggregate, we are grateful, because nothing can kill us faster than pathogenic bacteria. Furthermore, the fact that C.R. mimetics may be simply the side effects of a plants defenses, evolved primarily to target and suppress predation through growth inhibiting cellular signalling mimetics, suggests that what's good for fully grown higher animals, may not be good at all for very young children, and depending on inter-uterine, and lactation barriers, (excuse my made up terms there) may Not be a good idea for gestating/lactating females. So, we have a lot of work to do here. An explosion of published, peer reviewed papers are appearing in the journals about this subject. Each of these reasonable hypotheses can probably be resolved with a little research into newly published, peer reviewed journals. I think it would not be a bad idea to brain storm here, given the rapidly evolving insights published daily on this subject. So, an informal Request for Hypothesisseems a reasonable way to start work on this subject. I'm requesting all interested contributors to propose their resonable hypotheis here on this page, for the purpose of promoting discussion and debate, and then appropriate supporting the outcome of that process with well documented, peer reviewed articles on the subject. Under this plan, only after a reasonable consensus is reached, and only after a well referenced, peer reviewed journal article basis of support, should the work product migrate to the article page. That might be a way to cut down on time consuming debate. (Or maybe it will just double the work.) RGK (talk) 09:33, 5 October 2009 (UTC)

Circadian regulator CLOCK and C.R. Mimetics.
Professor Sassone-Corsi's work on the relationship of the Circadian regulator clock to sirtuin 1 activation is a fertile area for discussion. See http://www.faculty.uci.edu/profile.cfm?faculty_id=5402 and Doi, M., Hirayama, J. and Sassone-Corsi, P. (2006) Circadian regulator CLOCK is a Histone Acetyltransferase. Cell 125, 497-508. RGK (talk) 09:59, 5 October 2009 (UTC)

Hypothesis: Modern food processing and sterilization techniques have decimated C.R. Mimetic Compounds from the Western Diet
What I think has happened is that the absense of the C.R. Mimetic phytochemicals, including but not limited to, flavones, isoflavones, polyphenols, and bacterial defenses like rapamycin, and in such a short time, has caused a marked reduction in antioxidant enzyme induction, along with modern day stress, this has exacerbated ROS acting on increasing adipose lipid deposits, as will as lipid peroxidation in general. The effect on tumor and other cancer formations has been profound, primarily due to mechanisms described in the theories of mitogenesis and angiogenesis.

''Over the last roughly 50 years of increasing diet alteration / processing, we have been increasing the consumption of xenohormetic substances that increase cellular stress, while decreasing the consumption of whole grain, legume, fruits and vegetables rich in phytochemicals that improve the cellular resilience to stress. Even if we do consume fruits and vegetables, the modern agricultural methods have utilized pesticides and synthetic fertilizers that the food crops do not produce the same amount of beneficial phytochemicals.'' extracted from an article written by Jeffery Bland Ph.D., Metagenics RGK (talk) 09:59, 5 October 2009 (UTC)

Sub-hypothesis: Sirtuin 1 Activation Invokes MnZn Superoxide Dismutase(SOD2) Induction
More than anything else, this has convinced me of the merits C.R. mimetics. 71.105.250.25 (talk) 09:06, 5 October 2009 (UTC)

Sub-Hypothesis: Effect of Chemical Subsidies in Modern Agriculture
To maximize crop yields, we have fundimentally changed the natural expression of various naturally occurring chemicals in all agricultural products. When a plant has not been stressed by competitive predation because of the presence of xeno-antibiotic compounds (agricultural chemicals and fertilizers), logic suggests that the plant is less likely, or unlikely to express its own protective polyphenols (e.g. resveratrol). Thus, the undocumented side effect of the use of (xeno-chemos?) chemical subsidies has been devastating to presense of C.R. inducing flavones, isoflavones, probiotics, and polyphenols even in fresh produce. This would suggest that organically grown, and sustainable agricultural technology offer greater benefits to the consumer than previously thought If it can be documented here, this hypothesis may be the strongest supporting science for the use of organic and sustainable agriculture. Certainly, anecdotal observation supports the hypotheis. People who grow their own food look great. Native Japonese, strong equol producers, look much better than their non-equol producing cousins in Hawaii, etc. Anecdotal? Yes, Untrue. probably not. We need researchers to ferret this stuff out. 71.105.250.25 (talk) 09:06, 5 October 2009 (UTC) RGK (talk) 09:38, 5 October 2009 (UTC)

Sub-Hypothesis: C.R. Mimetics, The Missing Essential Nutrients
There is strong evidence emerging from research on cell signalling pathways that C.R. Mimetics may actually be more like 'essential nutrients' rather than non-nutritive static background chemicals. The overall effect of removing these phytochemicals over such a short period of time, and in such dramatic amounts is strongly suspected as a cause underlying increasing rates of metabolic syndrome, diabetes II, reactive oxygen species induced inflammatory responses, and more importantly, a major instigator of cell proliferation in what would otherwise have been minor incidence of self resolving cancers. Increased tumor formation from ROS via mitogenesis and the reduction of growth inhibiting cellular signalling may promote angiogenesis as well. Increased incidences of these diseases in both human and companion animal health is irrefutible. Now, we need to document evidence and support the hypothesis with peer reviewed journal articles. 71.105.250.25 (talk) 09:06, 5 October 2009 (UTC)

Xenohomesis
It's probably impossible to have an respectable article about C.R. mimetics without mentioning both Sinclair, et. al.'s xenohomesis hypothesis and competing but not mutually exclusive, naturally occuring plant and bacteria, anti-growth defenses; e.g. substances like estrogenic isoflavones, polyphenols including resveratrol, symbiotic-soil-bacterium producing rapamycin, all primarily appearing in plants and symbiotic bacteria ecosystems as competitive defenses against parasitic fungi, insects, etc. The proliferation of these strong anti growth factor throughout the plant genome, resulted in a beneficial, anti-aging cell signalling epigenetic activator in older, higher animals. Some good references are Sarah L. Hands, Christopher G. Proud, Andreas Wyttenbach, mTOR’s role in ageing: protein synthesis or autophagy, AGING, July 2009, Vol. 1. No 7 ;Blagosklonny; Inhibition of S6K by resveratrol: In search of the purpose 71.105.250.25 (talk) 09:06, 5 October 2009 (UTC)

'' "Xenohormesis" is derived from the word root "xeno" (foreign) and "hormesis" (control). Xenohormesis means altered cellular function due to exposure to foreign chemicals in the food supply, water and air. Our food contains countless potentially bioactive substances which are beyond the traditionally recognized macronutrients (proteins, carbohydrates and fats) and micronutrients (vitamins and minerals). Interestingly, some of these xenohormetic substances are beneficial while many are detrimental.'' citation extracted from an article by J.Bland Ph.D Metagenics. RGK (talk) 10:05, 5 October 2009 (UTC)

I am agree with this suggestion. I have found in my own experiments many effects in the direction of preventing body weight increase, lower hepatic lipid accumulation, etc. when a polyphenolic-rich extract was administered to a High-fat fed mice. Also in "Resultados Preliminares" section. (Thesis in Spanish). Regards Gustafmaler (talk) 11:17, 1 July 2017 (UTC)

Soy Isoflavone Diadzein and Metabolite S-Equol
Evidence is suggesting that diadzein and perhaps its metabolite s-equol are SIRT 1 activators. Ions, et. al; title something like=Is Soyabean an Activator of SIRT 1; British Journal of Nutrition, Sept or Oct 2009 (I'll find the citation) and their work was based upon Kyle A. Rasbach and Rick G. Schnellmann's 2008 paper Isoflavones Promote Mitochondrial Biogenesis. 71.105.250.25 (talk) 09:06, 5 October 2009 (UTC)

PPARy in Other candidate section
This sentence "Peroxisome proliferator-activated receptor gamma inhibitors, such as Rosiglitazone and ..." must be edited. Rosiglitazone is a full agonist fo PPARy, not an antagonist. As an example. Regards Gustafmaler (talk) 11:22, 1 July 2017 (UTC)