Studies Of Caloric Restriction, Resveratrol And Sirt1 Demonstrate A ?Metabotype’ Continuum From Cellular Rejuvenation To Aging To Cancer

Studies of Caloric Restriction, Resveratrol and SIRT1 Gene Regulation of Intermediary Metabolism and Mitochondrial Biogenesis Demonstrate a Requisite ‘Metabotype’ Continuum from Cellular Rejuvenation to Aging to Cancer, Independent of Cancer Cell Growth Factors, Suppressors or Immortalizers. by Gregory S. Bambeck Ph.D.  

Abstract 

In the early to mid twentieth century Otto Warburg hypothesized that cancer cells could be characterized by dramatically elevated glycolysis and mitochondrial respiratory deficiency locked in a relationship he called ‘aerobic glycolysis’. The respiratory deficiency claim was proven false and cancer cell biochemistry shifted its studies toward oncogenes, cell growth factors and their cascades, cancer cell growth suppressor systems, apoptosis, telomeric immortalization, cell recognition and adhesion mechanisms etc. Any global hypothesis devoted to mitochondrial inefficiency or dysfunction related to the anabolic and catabolic control requirements to cancer cell function, such as those proposed by G. Bambeck were refused funding or publication, and in fact, were quietly chaperoned out of the halls of science. Now, some 30 and some 50 years later, the pariahs may have been proven to be visionaries. Glycolytic blocking and retrafficking agents, such as dichloroacetate etc. can either kill or ‘renormalize cancer cells. Caloric restriction, the only known mechanism for extending life well beyond its normal span, in everything from roundworms to primates, is now known to rejuvenate aging cells and down regulate cancer cell initiation and growth by turning on a suite of 745, or more,   genes that renormalize glycolysis and initiate phagocytosis of inefficient mitochondria concomitant with biogenesis of efficient, new mitochondria. Resveratrol turns on the exact same suite(s) of genes, and by every measure, has the same cytological impact. The ‘metabotype’ continuum from juvenile cell, to aging cell, to cancer cell, make even more sense in an evolutionary context. 

Forward 

This is a general review article which is presented as a narrative. It is not intended for peer review, in part, for reasons contained in the abstract and the body of the text. That does not mean that this work is unimportant. In fact, it might be very important, because it connects together lines of research that converge on medical implications of great magnitude. It is written by a PhD scientist with over thirty fruitful years of scientific research under his belt, who hopes that he may have the time, later, to write a more formal article. This information should be gotten out there informally and quickly, rather than not to be gotten out at all.

There is no bibliography or references in this work, but at the end of this text, a short list of search engine words and suggested readings are provided, so that more than enough bibliography is provided to see ‘the big picture’ presented by the hypothesis contained, herein. This article is restricted to the basic catabolic and anabolic changes in intermediary metabolism and how they relate to juvenile, adult and cancer cells, because this area of cancer research has been left fallow. Other very important areas of research, such as the aforementioned cell growth factors etc., have tens of thousands of articles that may be referred to.

This article is devoted to an area of research that has been relegated to a backwater, in particular, in regards to cancer cell intermediary metabolics. If it had not been for anti-aging and life extension research results, stumbling through the metabolic ‘back door’, so to speak, some thirty years after a modified Warburg hypothesis, coupled with some new cancer metabolism blockers, the important connections could not have been made. Throughout history, serendipities and/or convergences have come together to form holistic emergent systems with more than just notable impact. Hopefully, this one of those times.

Lastly, this article is written a la Scientific American in that it is, hopefully designed to be understood by the educated lay person, while not short changing the serious scientist, too much. Professional jargon will be held to a minimum. It is my hope that a more in depth review won’t be necessary, if enough interest ensues. It would certainly be far more gratifying if interested parties would take up the discussion, or even initiate lines of investigation that might knit the outlines of these semi-integrated patches into a more complete fabric of either enhanced, or wholly new understanding. So, here we go, more or less ‘off the cuff’. 

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