The Anti-Aging Triad

By Stephen Holt

Th is book is a ground breaking review of the three most important scientifi c areas
of anti-aging medicine. Stephen Holt MD has navigated areas of conventional and
integrative medicine to produce a book that is valuable for both a layperson and
biomedical experts.

• Language: English
• Publisher: AuthorHouse
• Release date: Apr 1, 2011
• ISBN: 9781456755751

Book preview

© 2011 by Stephen Holt MD (in all languages)

No part of this book may be reproduced, stored in a retrieval system, or transmitted by any means without the written permission of the author.

Published by AuthorHouse 08/01/2011

ISBN: 978-1-4567-5576-8 (sc)

ISBN: 978-1-4567-5575-1 (ebook)

Printed in the United States of America

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and such images are being used for illustrative purposes only.

Certain stock imagery © Thinkstock. This book is printed on acid-free paper.

No part of this publication may be reproduced or stored in a retrieval system or transmitted in any form without the prior written consent of the publisher and author Stephen Holt MD. Quotations from the book may be made in any literature, providing that the source of the information is referenced. No responsibility is assumed by the author or publisher for any injury and or damage to property of any kind as a matter of product liability, negligence or otherwise or from the use of any suggestions, methods, products, treatments, instructions, ideas or speculations made in this book. This book is not a dietary supplement label or a treatment handbook.

Editorial assistance: Carl Perry

KEY WORDS: 1. Stem cells 2. Telomeres 3. Telomerase 4. Calorie Restriction 5. Calorie Restriction Mimetics 6. Integrative Medicine 7. Live Cell Therapy 8. Metabolic Syndrome X 9. Diabetes mellitus 10. Photoaging 11. Dietary Supplements 12. Antiaging 13. Longevity

"Don’t shoot me,

I am only the piano player"

Sir Elton John, 1973

www.stephenholtmd.com

Contents

Foreword I: Robert Goldman, MD, PhD

Foreword II: Th omas V. Taylor, MD, FRCS

Foreword III: Michael Klentze, MD

Foreword IV: Mitchell Ghen, DO, PhD

Foreword V: Paul Th ai, DPM, ND

Preface: Stephen Holt, MD, PhD, DSc, LLD.

Introduction: The Quest For Longevity

Part A: Calorie Restriction Mimetics

Part B: Telomeres

Part C: Stem Cell Sciences

Appendix A: Metabolic Syndrome X: Syndrome X, Y, Z…?

Appendix B: Nutraceutical Approaches To Antiaging

Appendix C: The Power Of Synergy

Appendix D: Live Cell Therapy: The Birth Of Modern Biological Treatments?

Appendix E: Photoaging

Epilogue

Glossary Of Terms

About The Author

Other Books By The Author

FOREWORD I

Robert Goldman MD, PhD, Chairman, American Academy of Anti-Aging Medicine (A4M), World Anti-Aging Academy of Medicine, Boca Raton, Florida

Stephen Holt MD is a pioneer of Integrative and Anti-aging Medical Sciences, a best selling author, revered clinician, researcher and educator. This book focuses on Dr. Holt’s belief in calorie restriction, telomere function and stem cell treatments as the most important emerging scientific areas in longevity medicine. In these writings, innovative areas of science are presented in a manner that is often easily understood by a layperson.

The principles of Integrative Medicine are only starting to interface with stem cell sciences and in this book Dr. Holt bridges the gap. Topics are reviewed in a way that sorts speculation from science and these writings are hard-wired to scientific literature. This work will be valuable to healthcare-givers, including medical specialists, because it reflects a move towards natural therapeutics, without dismissing the obvious value of allopathic medical interventions.

Many items in this book represent viable approaches to attempt to enhance human lifespan or promote wellness in the elderly and they address concepts of advanced preventive medicine. Dr. Holt predicts a time when external influences and interventions can be used to recruit endogenous stem cells to function as a highly efficient internal body-repair kit. He highlights the value of supporting telomere structure for longevity promotion, with cautious optimism. Furthermore, he presents compelling arguments about calorie restriction and its documented life-extending properties. In addition, Dr. Holt discusses calorie restriction mimetics. These mimetic compounds may act in a favorable manner to produce biological changes that support youthful body functions.

Within Dr. Holt’s book is a repeated call for further research. Stephen Holt MD is not over-exuberant in his support for some suggestions to enhance life span, but he is dedicated to his chosen triad as the future of longevity medicine. Dr. Holt is quite willing to discuss disadvantages and limitations of some of these proposed interventions for longevity promotion. This work is a valuable contribution to the modern movement of anti-aging and regenerative medicine. It will help to satisfy the increasing thirst for knowledge about the modern anti-aging revolution. This quest for knowledge exists among healthcare consumers and physicians, alike.

Robert Goldman MD, PhD

Boca Raton, Florida

September 2010

FOREWORD II

Thomas V. Taylor, MD, ChM, FRCS, Clinical Professor of Surgery, University of Texas, and Baylor College of Medicine, Houston, TX

I am pleased to introduce this book on new concepts in longevity medicine, with its focus on Integrative Medicine. Stephen Holt MD requires little introduction to the international medical community. He is a pioneer of Integrative and Anti-aging Medicine, with four decades of clinical, academic and medical research experience. Dr. Holt is a board certified gastroenterologist and internist, with advanced and higher training in clinical pharmacology and toxicology.

While Dr. Holt has taught, researched and contributed to many aspects of therapeutics and longevity medicine, I am intrigued by his selection in this book of three topical areas (the triad) of longevity medicine. He characterizes the triad as forming interconnecting foundations for anti-aging interventions in the new millennium. This book introduces several areas of scientific research including: the role of calorie restriction in longevity promotion, the importance of telomere function in the timing of the onset of aging and the promise of stem cell science for regenerative medicine. Dr. Holt takes complex scientific frontiers and presents them in a readily understandable manner.

With eloquence, Dr. Holt highlights areas of modern anti-aging science without inaccurate oversimplification. In fact, this book has key references and content that will not bore the specialist healthcare-giver. In brief, these writings have depth and innovative ideas, especially in the field of natural healthcare. This book integrates facets of natural medicine into the complex science of telomeres, stem cells and calorie restriction. These writings demonstrate the worthiness of his election to Who’s Who in Antiaging Medicine.

Please read this book in health and pause to think about some of its apparent simple statements. Dr. Holt has a pleasing and provocative way of discussing science, with just the right touch of humor. He tackles concepts of evidence-based medicine and shows his liberal acceptance of Integrative Medicine. His statements are based on considerable medical experience and a selected synthesis of modern literature. The author reveals his mind that is equivalent to a medical encyclopedia, as he sorts science from speculation. Anti-aging medicine is evolving into one of the most important areas of subspecialty clinical practice and Dr. Holt’s selection of the Antiaging Triad is timely.

Thomas V. Taylor MD

Houston, Texas

July 2010

FOREWORD III

Michael Klentze, MD, Vitallife Wellness Center in Bangkok, President European Society of Antiaging Medicine

Stephen Holt, MD is the leading international expert in antiaging medicine. In this book, he presents the new concepts on the relationship between stem cells, telomeres and calorie restriction. As a natural extension to these very important areas of longevity medicine, Dr. Holt reviews key initiatives for antiaging, including a combat against metabolic Syndrome X (Syndrome X, Y, Z…), photoaging and he addresses nutraceutical interventions for antiaging.

The science of antiaging is progressing rapidly with an increasing evidence-base to apply various therapeutic interventions. I have been impressed by Dr. Holt’s contribution to the world societies of anti-aging medicine and the European Society of Antiaging Medicine was pleased to have Dr. Holt join its board in 2010. As many centers of excellence develop multipronged approaches for the promotion of longevity, this book on The Anti-Aging Triad is a major advance.

Stephen Holt MD has worked for many years as a pioneer of Integrative Medicine to place alternative medical interventions at an interface with conventional medicine. His second accomplishment is to have provided more than twenty books that assist in the education of both the layperson and physician on natural pathways to health. While sections of this book are necessarily complex, it provides an objective overview of the integration of natural therapeutics with conventional science. It is with great pleasure that I introduce this book as a valuable source of innovative ideas and new medical concepts.

Michael Klentze, MD

Bangkok, October 2010

FOREWORD IV

Mitchell Ghen, DO, PhD, Lake Mary, Florida, Stem Cell Clinician

This book provides proof of the ever changing and expanding knowledge base of antiaging medicine. This complex knowledge base is creating increasing difficulty in the understanding of medical efforts to promote longevity and it provides a zone of medicine that is difficult to navigate. As a baby boomer researcher and clinician, I have to focus on the embryonic science of antiaging and this book foots the bill as an introduction to the most important areas of antiaging interventions. Collective experiences have shown that single medical discipline treatments or interventions have not met expectations and many have fallen quite short of the mark. This book shows the power of comprehensive care in the field of the promotion of wellness in the elderly. It is a masterpiece of Integrative Medicine.

Any person who wants to grasp the non-stochastic nature of aging may have to admit that there is a deficiency in our current understanding about body chemistry and physiology. Those individuals who embrace a multi-disciplinary approach appear to possess the greatest sense of balance in their approach to antiaging. In this book, Stephen Holt MD paves the way to multi-pronged interventions in the anti-aging arena. Many scientists and clinicians remain hopeful with optimistic caution about many proposed ways of staying young forever.

Stephen Holt MD has a keen eye for detail in his writing and he is a dynamo of lateral medical thoughts. In this book, Dr. Holt brings us a clear, concise and masterful insight into three areas of medicine that he identifies as the platform on which antiaging technologies must be based. Dr. Holt presents compelling arguments that these areas form major frontiers that can improve both quality and quantity of lifespan. I recall the day when I first discussed this work with Dr. Holt and offered to write a foreword to his new book. I am delighted with the outcome.

Dr. Holt is a frequent lecturer in every keynote forum at many antiaging societies on an international basis. After listening intently to Dr. Holt, I realized that he does his homework and, in this case, he has identified those areas that hold the greatest potential for significant advances in regenerative medicine. Stephen Holt MD illustrates how evidence-based areas of integrative medicine interconnect in his concepts of The Antiaging Triad. This book goes beyond the triad by addressing important issues such as photoaging and the identification of Metabolic Syndrome X (Syndrome X, Y, Z…of Holt, 2000) as a key antiaging initiative.

I identify most closely with Part C of this book which covers many basic aspects of stem cell transplantation or replacement. I have performed several hundred stem cell transplants. In addition, my colleagues and I have performed much individual research that has led to the conclusion that average nutritional or hormonal supplement interventions for antiaging are not universally successful and some have questionable validity. Surely, using the synergistic combination replacement of hormones, lifestyle changes and stem cell therapies have an excellent chance of improving overall cellular health. Synergy is the powerful message found within this book and it is reviewed in a lighthearted manner in Appendix C.

Even though my colleagues and I have witnessed many regenerative changes with stem cell treatments, the challenge was to insure that donor cells became effectively implanted. Dr. Holt raises important issues about chemical messengers and growth factors that are delivered by stem cells that may not engraft. Dr. Holt talks about the reciprocal harmony of life (as described by Claude Bernard in the late Victorian Era); and he uses these early concepts to reinforce the need for stem cells to produce functional tissues. Dr. Holt is a true scholar of alternatives.

Dr. Holt acknowledges a need for stem cells to survive environmental perils and his comments about stem cell treatments being part of a more complete biological treatment program are well justified. Practitioners of stem cell therapies often overlook comprehensive aspects of patient preparation and care during all forms of transplantation.

I was intrigued that Dr. Holt provides a very modern viewpoint on live cell therapy, but he is very cautious about supporting this therapy, without further evidence-based observation. For the first time in the medical literature, Dr. Holt has attempted to provide multiple hypotheses on how animal fetal cell transplantation (live cell therapy) could deliver chemical messengers in a manner that could favorably alter body structures and function. Dr. Holt justifies his inclusion of information about live cell therapies in Appendix D by revealing the increasing use of this treatment on an international basis and reminding us that several million people have undergone this therapy in one century of its use. The reactivation of interest in live cell therapy is intriguing.

Part B of this book illustrates how telomere technology may offer protection against premature cellular demise and help withstand external forces that lead to apoptosis. Alteration of telomerase activity and related technologies continue to inch us towards extended lifespan. In fact, many baby boomers want to embrace the idealistic status of superhuman immortality.

Dr. Holt’s analysis of many antiaging technologies points to only one concept that seems to be able to stand up to great scrutiny. Dr. Holt describes calorie restriction as a true life extender and he aptly explains its actions in Part A of this book. It is clear that if you eat less or less often then much information from animal studies show positive effects on longevity. This work has been extrapolated to humankind, with confirmation in recent studies. It is believed that societies and cultures who fast may have longer than expected life expectancy.

Fasting and dietary calorie control present major compliance problems and Dr. Holt handles the concept of calorie restriction combined with the use of calorie mimetics in a very appealing manner. While Dr. Holt talks about failure to maintain dietary calorie restriction, I find his suggestions about taking calorie restriction mimetic supplements to be very practical. This is a very promising area of longevity medicine.

Please read this book with optimism. Take off your shoes, relax and get ready to dive into a reality-based and very plausible triad theory. In my opinion, this may be the best thought-out work, so far, in antiaging and regenerative medicine. As an individual who has spent a large part of my career pursuing stem cell technologies, I applaud the work of Stephen Holt MD on the multiple-faceted approaches that he has presented in this book. For certain, the quoted science supports each of the methodologies presented; and the way Stephen Holt writes about them challenges both healthcare professionals and the lay public to engage in some degree of serious thought.

I have witnessed the world of antiaging science change ever so quickly. I recommend that all mature individuals consider getting on the antiaging technology bullet train or they may be left behind and subject to premature morbidity or mortality. In any case, please enjoy the antiaging triad and use it as a mentorship to define how to live a long and healthy life using exciting new technology.

Mitchell Ghen, DO, PhD

Florida, September 2010

FOREWORD V

Paul Tai, DPM, ND, President, Antiaging Society of Brazil, Chairman,

Stem Cell Summit , Brazil

This book is a major contribution to the global practice of antiaging medicine. Stephen Holt MD is recognized internationally for his contribution to the development and expansion of the subspecialty practice of Integrative Medicine. In this book, Dr. Holt has characterized three areas of antiaging science that are among the most important areas of interest in longevity medicine.

As the President of the antiaging society of Brazil, I can strongly endorse this work which includes important areas of Integrative Medicine practice that are directly relevant to the maintenance of long and healthy life. The section of this book on stem cells represents a current overview that draws from existing scientific literature and it provides speculation about the future of stem cell research. Our stem cell summit meetings in Brazil have been extremely successful over the past two years and this area of science continues to gain momentum in all countries.

Dr. Holt has distinguished himself with his description of nutritional and lifestyle approaches to combat Syndrome X. I was impressed when Dr. Holt coined the term Syndrome X, Y, Z… to illustrate the protean manifestations of metabolic syndrome. Syndrome X is a major area of my own interest where scientists have now discovered more about the underlying pathophysiology of obesity. Many healthcare givers realize that Stephen Holt MD described what is now called the glycemic index in the Lancet in 1979. Following these initial groundbreaking observations, Dr. Holt has presented many nutritional factors, over a period of two decades, to combat Syndrome X.

Stephen Holt MD has drawn everyone’s attention to the far reaching consequences of Syndrome X (which he has defined under the new terms Syndrome X, Y, Z…). This expanded view of metabolic Syndrome X is consistent with the knowledge that this constellation of problems found within Syndrome X results in death from all causes. In fact, Dr. Holt has been singularly responsible for drawing the attention of the antiaging community to Syndrome X as a key issue to be tackled for longevity promotion.

The importance of calorie restriction and related mimetic compounds is revolutionizing approaches to the nutritional management of longevity medicine. The emerging importance of telomere structure and function is clear in modern scientific literature and it forms the basis of new zones of science in antiaging medicine.

I recommend this book highly and it is of general interest for all physicians and laypersons who wish to delve into the new evidence-based sciences that are contributing to our increasing knowledge base to antiaging medicine. Antiaging tactics are very important as humankind lives longer with their quest for health in later stages of life.

Dr. Paul Tai, DPM, ND

October 2010

PREFACE

Stephen Holt, MD

This book asks and begs the unanswerable question Why do we age? The inability to respond with brevity to this question rests with the knowledge that aging involves multiple factors and issues. Credible or cast iron descriptions of means and ways of increasing average and maximum lifespan in humankind are limited by the necessity for lengthy clinical studies to provide proof of any proposed techniques for anti-aging. In this book, I have chosen three areas of anti-aging sciences (the triad) that I believe have the greatest promise to provide an understanding of aging and create options for anti-aging strategies here and now. These areas form the interconnecting triad of telomeres, stem cells and aspects of calorie restriction. In these writings, I attempt to address anti-aging medicine in a manner that permits logical interventions for longevity or regenerative medicine.

While the staunch scientist may describe some of the contents of this book as mere speculation, others are driven to try new interventions for longevity promotion, most often with the desire to do no harm. My underlying approach to longevity promotion involves what I believe to be safe advice on how to use current knowledge to extend human survival.

Although I am limited by many incomplete scientific studies to make firm conclusions, there will be a day when stem cell sciences, telomere/telomerase modulation and calorie restriction are used to turn back the clock on aging. This day may be hopefully around the corner, rather than a distant promise. If we ever approach the fountain of youth, we will realize that this fountain involves a complex cascade of different interventions to induce longevity and not some magical single approach. There is no unitary holy grail of eternal youth and Ponce de Leon was probably on a wild goose chase.

When I started to delve into the science of telomeres, stem cells and calorie restriction, I perceived my writings to be a trilogy. A trilogy is a literary work made up of three parts, each of which is complete by itself. By no means are calorie restrictions, telomere tampering or stem cell treatments distinct or complete subjects in the field of anti-aging medicine. They form a triad or group of three closely related matters.

I trust that readers will tolerate my echolalia when I state that aging is a multi-factorial circumstance, with multiple mechanisms of aging that require multi-pronged interventions. In these truncated writings, I hope to portray how the selected components of my chosen triad may interact to provide synergistic interventions that may promote long life with health (longevity). This book contains intentional repetition, in order to ground the non-expert in the concepts. Repetition supports learning.

Perhaps the only current, applicable, evidence-based approach to anti-aging is calorie restriction. Significant dietary restriction of calories, without the induction of malnutrition, results in favorable changes in body structures and functions that cause an increase in maximum and average lifespan. These phenomena have been noted in all species of organisms that have been researched. Such observations have been made in many living organisms ranging from yeasts, through worms to mammals to primates and to humans. There is a recognition that calorie restriction delays the onset or progression of many diseases or disorders, e.g. diabetes mellitus, renal disease, autoimmune disorders, neurodegenerative diseases and cancer…to name a few. In turn, our international waist line expansion is contributing to premature extinction (the pot-bellied human dinosaur).

As scientists started to unravel the favorable biological consequences of dietary calorie restriction, a search commenced to find compounds (drugs or natural agents) that could mimic these consequences, in the absence of a need to inflict punative dieting. Hence, the novel concept of calorie restriction mimetics was born. These mimetics may enhance lifespan by indirect means. This may occur as a consequence of the duplication of the beneficial effects of actual calorie restriction on human physiology. These notions are not far-fetched.

In this book, I shall present my speculation on the value of the use of calorie restriction mimetics in modern anti-aging medical practice. In brief, I reiterate that calorie restriction mimetics afford a strong promise of achieving similar benefits to those observed with significant reductions of calorie intake by inducing molecular (biochemical or genetic) events that are associated with the act of significant calorie restrictions (at least 30%-50% lower calorie intake than ad libitum feeding).

I propose that a calorie restriction mimetic may be quite effective, if it is used with tolerable levels of dietary restriction that do not induce failure of reasonable compliance with a diet and avoidance of nutrient deficiencies. The appeal of the mimetic in our society is highlighted by the knowledge that compliance with significant dietary (calorie) restrictions poses a monumental task for many people. Society, medicine and politics have failed in attempts to materially alter the eating habits of any nation, in a beneficial manner. That said, the fast food culture has had a global and negative impact.

Alongside the benefits of calorie restriction (CR) or the putative benefits of calorie restriction mimetics (CRM) has been an increasing understanding of the epidemic of Metabolic Syndrome X (obesity, hypertension, dsylipidemia in variable combinations, with insulin resistance). In Syndrome X, one encounters a constellation of problems that cause accelerated aging. Syndrome X accounts for a large proportion of premature morbidity (illness) and premature mortality (death) in industrialized societies (see Appendix A.) It is a disorder of premature aging and it is a common forerunner to Type II diabetes. Diabetes (Type II) is another disorder that may be best classified as a disease of premature aging. In this book, I link the concepts of calorie restriction as a combat against the epidemic of Syndrome X, prediabetes and Type II diabetes mellitus (Appendix A).

I need to amplify the interconnections of anti-aging strategies that I introduced earlier in this dialogue. Many calorie restriction mimetics CRM (and calorie restriction itself) act to regulate glucose metabolism (homeostasis). This common effect of calorie restriction mimetics on glucose homeostasis is more than a coincidence in our modern society, where it is estimated that 70 million individuals in the USA have Metabolic Syndrome X. This disorder is underpinned by the occurrence of insulin resistance and it occurs in various stages of evolution towards a diabetic diathesis. As I move to discuss