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Research Blog - A Broader View of Genomics

Monday, May 9, 2011 9:56:18 PM America/New_York

The New Era of Health and Medicine as an Information Technology is Broader than Individual Genes

- Ray Kurzweil, September 2, 2010

There has been recent disappointment expressed in the progress in the field of genomics. In my view this results from an overly narrow view of the science of genes and biological information processing in general.

It reminds me of the time when the field of "artificial intelligence" (AI) was equated with the methodology of "expert systems." If someone referred to AI they were actually referring to expert systems and there were many articles on how limited this technique was and all of the things that it could not and would never be able to do. At the time, I expressed my view that although expert systems was a useful approach for a certain limited class of problems it did indeed have restrictions and that the field of AI was far broader. The human brain works primarily by recognizing patterns (we have about a billion pattern recognizers in the neocortex, for example) and there were at the time many emerging methods in the field of pattern recognition that were solving real world problems and that should properly be considered part of the AI field. Today, no one talks much about expert systems and there is a thriving multi-hundred billion dollar AI industry and a consensus in the AI field that nonbiological intelligence will continue to grow in sophistication, flexibility, and diversity.

The same thing is happening here. The problem starts with the word "genomics." The word sounds like it refers to "all things having to do with genes." But as practiced it deals almost exclusively with single genes and their ability to predict traits or conditions, which has always been a narrow concept. The idea of sequencing genes of an individual is even narrower and typically involves individual single-nucleotide polymorphisms (SNPs) which are variations in a single nucleotide (A, T, C or G) within a gene, basically a two bit alteration.

I have never been overly impressed with this approach and saw it as a first step based on the limitations of early technology. As Dr. Grossman points out in his recent H+ article "Rethinking the Promise of Genomics," there are some useful SNPs such as Apo E4 but even here it only gives you statistical information on your likelihood of such conditions as Alzheimer's Disease and macular degeneration based on population analyses. It is certainly not deterministic and has never been thought of that way. As Dr. Venter points out in his Spiegel interview, there are hundreds of diseases that can be traced to defects in individual genes, but most of these affect developmental processes. So if you provide a medication that reverses the effect of the faulty gene you still have the result of the developmental process (of, say, the nervous system) that has been going on for many years. You would need to detect and reverse the condition very early, which of course is possible and a line of current investigation.

To put this narrow concept of genomics into perspective, think of genes as analogous to lines of code in a software program. If you examine a software program, you generally cannot assign each line of code to a property of the program. The lines of code work together in a complex way to produce a result. Now it is possible that in some circumstances you may be able to find one line of code that is faulty and improve the program's performance by fixing that one line or even by removing it. But such an approach would be incidental and accidental, it is not the way that one generally thinks of software. To understand the program you would need to understand the language it is written in and how the various lines interact with each other. In this analogy, a SNP would be comparable to a single letter within a single line (actually a quarter of one letter to be precise since a letter is usually represented by 8 bits, and a nucleotide by 2 bits). You might be able to find a particularly critical letter in a software program, but again that is not a well motivated approach.

The collection of the human genome was indeed an exponential process with the amount of genetic data doubling each year and the cost of sequencing coming down by half each other. But its completion around 2003 was just the beginning of another even more daunting process, which is to understand it. The language is the three-dimensional properties and interaction of proteins. We started with individual genes as a reasonable place to start but that was always going to be inherently limited if you consider my analogy above to the role of single lines in a software program.

As we consider the genome, the first thing we notice is only about 3 percent of the human genome codes for proteins. With about 23,000 genes, that means 23,000 proteins and, of course, these proteins interact with each other in complicated pathways. A trait in a complex organism such as a human being is actually an emergent property of this complex and organized collection of proteins. The 97 percent of the genome that does not code for proteins was originally called "junk DNA." We now understand that this portion of the genome has an important role in controlling and influencing gene expression. It is the case that there is less information in these non coding regions in it is replete with redundancies which we do not see in the coding regions. For example, one lengthy sequence called ALU is repeated hundreds of thousands of times.

As Dr. Grossman points out gene expression is a vital aspect of understanding these genetic processes. The noncoding DNA plays an important role in this, but so do environmental factors. Even ignoring the concept that genes work in networks not as individual entities, genes have never been thought of as deterministic. The "nature versus nurture" discussion goes back eons. What our genetic heritage describes (and by genetic heritage I include the epigenetic information that influences gene expression) is an entity (a human being) that is capable of evolving in and adapting to a complex environment. Our brain, for example, only becomes capable of intelligent decision making through its constant adaptation to and learning from its environment.

To reverse-engineer biology we need to examine phenomena at different levels, especially looking at the role that proteins (which are coded for in the genome) play in biological processes. In understanding the brain, for example, there is indeed exponential progress being made in simulating neurons, neural clusters, and entire regions. This work includes understanding the "wiring" of the brain (which incidentally includes massive redundancy) and how the modules in the brain (which involve multiple neuron types) process information. Then we can link these processes to biochemical pathways, which ultimately links back to genetic information. But in the process of reverse-engineering the brain, genetic information is only one source and not the most important one at that.

So genes are one level of understanding biology as an information process, but there are other levels as well, and some of these other levels (such as actual biochemical pathways, or mechanisms in organs including the brain) are more accessible than genetic information. In any event, just examining individual genes, let alone SNPs, is like looking through a very tiny keyhole.

As another example of why the idea of examining individual genes is far from sufficient, I am currently involved with a cancer stem cell project with MIT scientists Dr. William Thilly and Dr. Elena Gostjeva. What we have found is that mutations in certain stem cells early in life will turn that stem cell into a cancer stem cell which in turn will reproduce and ultimately seed a cancer tumor. It can take years and often decades for the tumor to become clinically evident. But you won't find these mutations in a blood test because they are mutations originally in a single cell (which then reproduces to create nearby cells), not in all of your cells. However, understanding the genetic mutations is helping us to understand the process of metastasis, which we hope will lead to treatments that can inhibit the formation of new tumors. This is properly part of gene science but is not considered part of the narrow concept of "genomics," as that term is understood.

Indeed there is a burgeoning field of stem cell treatments using adult stem cells in the positive sense of regenerating needed tissues. This is certainly a positive and clinically relevant result of the overall science and technology of genes.

If we consider the science and technology of genes and information processing in biology in its proper broad context, there are many exciting developments that have current or near term clinical implications, and enormous promise going forward.

A few years ago, Joslin Diabetes Center researchers showed that by inhibiting a particular gene (which they called the fat insulin receptor gene) in the fat cells (but not the muscle cells as that would negatively affect muscles) enabled caloric restriction without the restriction. The test animals ate ravenously and remained slim. They did not get diabetes or heart disease and lived 20 percent longer, getting most of the benefit of caloric restriction. This research is continuing now focusing on doing the same thing in humans, and the researchers whom I spoke with recently, are optimistic.

We have a new technology that can turn genes off, and that has emerged since the completion of the human genome project (and which has already been recognized with the Noble prize), which is RNA interference (RNAi). There are hundreds of drugs and other processes in the development and testing pipeline using this methodology. As I said above, human characteristics including disease result from the interplay of multiple genes, there are often individual genes which if inhibited can have a significant therapeutic effect (such as we might disable a rogue software program by overwriting one line of code or one machine instruction).

There are also new methods of adding genes. I am an advisor (and board member) to United Therapeutics which has developed a method to take lung cells out of the body, add a new gene in vitro (so that the immune system is not triggered which was a downside of the old methods of gene therapy), inspect the new cell, and replicate it several million fold. You now have millions of cells with your DNA but with a new gene that was not there before. These are injected back into the body and end up lodged in the lungs. This has cured a fatal disease (pulmonary hypertension) in animal trials and is now undergoing human testing. There are also hundreds of such projects using this and other new forms of gene therapy.

As we understand the network of genes that are responsible for human conditions, especially reversible diseases, we will have the means of changing multiple genes, and turning some off or inhibiting them, turning others on or amplifying them. Some of these approaches are entering human trials. More complex approaches involving multiple genes will require greater understanding of gene networks but that is coming.

There is a new wave of drugs entering trials, some late stage trials, that are based on gene results. For example, an experimental drug PLX4032 from Roche is designed to attack tumor cells with a mutation in a particular gene called BRAF. For patients with this genetic variant, 81 percent of patients with advanced melanoma had their tumors shrink (rather than grow) which is an impressive result for a form of cancer that is generally resistant to conventional treatment.

There is the whole area of regenerative medicine from stem cells. Some of this is now being done from adult autologous stem cells. Particularly exciting is the recent breakthrough in induced pluripotent stem cells (IPSCs). This involves using in-vitro genetic engineering to add genes to normal adult cells (such as skin cells) to convert them into the equivalent of embryonic stem cells which can subsequently be converted into any type of cell (with your own DNA). IPSCs have been shown to be pluripotent, to have efficacy, and to not trigger the immune system because they are genetically identical. IPSCs offer the potential to repair essentially any organ from hearts to the liver and pancreas. These methods are part of genetic engineering which in turn is part of gene science and technology.

And then of course there is the entire new field of synthetic biology which is based on synthetic genomes. A major enabling breakthrough was recently announced by Craig Venter's company in which an orgasm with a synthetic genome (which previously existed only as a computer file) was created. This field is based on entire genomes not just individual genes and it is certainly part of the broad field of gene science and technology.

The goal is to create organisms that can do useful work such as produce vaccines and other medicines, biofuels and other valuable industrial substances.

You could write a book (or many books) about all of the advances that are being made in which knowledge of genetic processes and other biological information processes play a critical role. Health and medicine used to be entirely hit or miss without any concept of how biology worked on an information level. Our knowledge is still very incomplete, but our knowledge of these processes is growing exponentially and that is feeding into medical research which is already bearing fruit. To focus just on the narrow concepts that were originally associated with "genomics" is as limited a view as the old idea of AI being just expert systems.

0 Comments | Posted in Ray and Terry Research By Eric Huang

Research Blog - Increasing Your Alkalinity

Monday, May 9, 2011 9:54:51 PM America/New_York

We have discussed how the body’s natural metabolic processes create acidic waste products, and, for optimal health, you need to restore your alkaline reserves. An effective way to do this is by drinking alkaline water, produced by a water alkalinizing machine This device, which looks like a coffee percolator, contains an electrical ionization system to split water into its acidic and alkaline portions. The alkaline water should be used for drinking and food preparation. The water’s alkalinity can be adjusted, and you should increase the level gradually to a pH between 9.5 and 10, which will provide a powerful detoxification treatment. We recommend that you drink 8 to 10 glasses per day of this alkaline water. It is one of the simplest and most powerful things you can do to combat a wide range of disease processes. The acidic water produced by the alkaline water machine from a separate outlet need not go to waste—it’s perfect for cleansing your skin. It’s also ideal to use for watering plants, which thrive in an acidic environment.

Excellent water alkalinizing devices (as well as a line of far infrared saunas, excellent for detoxification) are available thru High Tech Health.
Certain teas have alkalinizing effects on the body too.

Research Blog - Are Vitamins Beneficial?

Monday, May 9, 2011 9:54:01 PM America/New_York

Reporters sometimes write slanted articles that mislead the public on the uses and potential benefits of vitamins and nutritional supplements. Numerous studies indicate the nutritional causes of disease and the many ways in which supplements support wellness, but slanted reports often overlook the bigger picture. Vitamins should not be considered a "quick fix." However, taken in conjunction with a healthy lifestyle, many supplements have been shown to have properties that help ward off disease. To ignore the valid implications of years and volumes of detailed research is to ignore the true complexities of human health.


Terry Comments on Multivitamin Studies
December 30, 2013

Along the same lines of the media not disseminating studies that show problems with conventional medicine, please see: http://www.upi.com/blog/2013/12/27/No-surgery-produced-the-same-results-as-knee-surgery-according-to-Finnish-study/9771388174500/

This was an amazing study where patients either underwent “real” surgery to repair/remove knee cartilage or sham surgery where they had the same incisions and “pretend” operative movements (as they were awake). Study was done in Finland as I doubt it could have been approved in the US.

Placebo patients reported a greater degree of satisfaction than “real” patients.

This surgery is done half a million times a year in the US. At, say, $25,000 per procedure (probably too low), this is $12.5 billion of surgery – with all the pain, risk of infection, etc. associated with surgery – shown to be no more effective than placebo.

Even worse, in my experience, patients who have meniscal cartilage removed from their knees are MUCH more likely to wear down the cartilage covering the ends of their bones, resulting in often severe arthritis and need for joint replacement surgery years down the line.

I have seen no mention of this study in any media.

If a complementary treatment, say acupuncture, were shown not to be more helpful than placebo, the odds are that it would receive widespread press coverage.

By cherry picking which studies they publish, the illusion created is that conventional treatments work, while alternative therapies (including supplements) do not.

Here is a study coming out of the large and well respected Women’s Health Initiative showing positive results for supplements and breast cancer. Unfortunately, the media has largely ignored it. Abstract: http://link.springer.com/article/10.1007/s10549-013-2712-x


Ask Ray: Supplement Study in WSJ is Misleading
December, 2013

The study quoted by The Wall Street Journal is misleading. It only looked at low potency (and low quality) supplement combinations and set a very high bar requiring dramatic reductions in cardiovascular disease and other conditions.

There is no way that a routine commercial, low potency, low quality vitamin combination is going to meet that bar.

In terms of contraindicated substances, there are potentially harmful ingredients in some combinations. Iron is generally harmful for men in terms of promoting oxidation.

Vitamin A is potentially harmful, people should take its precursor Beta Carotene. What goes for “Vitamin E” in most commercial formulations is not vitamin E at all but Alpha Tocopherol, which is only one of the eight factions of vitamin E. Alpha Tocopherol suppresses Gamma Tocopherol, which is the faction found naturally in food and the most important type.

A better recommendation is to take “mixed tocopherols,” which is what I take..

For more: http://www.kurzweilai.net/ask-ray-supplement-study-in-the-wall-street-journal-is-misleading


Not So Fast… Calcium Report is Flawed
August, 2010

A recent report cast doubt on calcium supplements. Ray & Terry do not recommend aggressive calcium supplementation. However, calcium is essential for bone health, particularly in women as they age, that it is important to realize there are shortcomings in this recent report. The study did not separate men and women, for example, who have very different osteoporosis and heart disease risk rates.

Men have a higher instance of heart attacks, but women have a higher instance of osteoporosis. Ray & Terry offer gender-specific calcium recommendations with this in mind.

Before avoiding all calcium supplements, we advise considering personal circumstances and deciding what's best for the individual. Women 50-70 with a family history of osteoporosis, who do not eat any dairy, for example, should consider calcium supplements.

Scott, Sophie. "Calcium supplement heart attack study 'absurd'." ABC News. Aug 3, 2010. http://www.abc.net.au/news/stories/2010/08/03/2972399.htm


Antioxidant Supplements Won't Hurt Us, But Misinformation Might By James J. Gormley May 3rd, 2008

Lately we've heard quite a lot about how nutritional supplements, including antioxidant vitamins, are regarded by a few scientists as a great danger—or so we might gather from recent media coverage that has treated us to such fear-mongering headlines as "Potential for harm in dietary supplements"1, "Vitamin pills may do more harm than good" 2 and "Why some popular pills might kill you" 3.

The scientific review to which these sensationalistic stories refer was a meta-analysis in the Cochrane Database of Systematic Reviews 4. A meta-analysis is supposed to be careful re-review of many studies whose results are pooled together.

The Cochrane Database meta-analysis, authored by Goran Bjelakovic and others, is an updated version of a review that originally appeared in the Journal of the American Medical Association 5 that had been roundly criticized by scientists.

While 67 clinical trials were included in this new review, most people are not aware that 748 trials were excluded for a number of reasons, including 405 studies that failed to show anybody died 6.

One could persuasively argue that the authors of this review only included studies which could be molded to support the viewpoint that antioxidant vitamins are dangerous.

Dr. Bjelakovic has made no bones about his skeptical attitude towards dietary supplements. In 2007, he co-authored an article in the Journal of the National Cancer Institute entitled: "Surviving Antioxidant Supplements" 7 and has posted an article on a newspaper syndicate entitled "Do antioxidant supplements work?" 8.

While meta-analyses, when properly conducted, can be an insightful tool; when ill used they are subject to bias by those who hold pre-determined conclusions and are seeking a way to force studies into them.

A wide body of scientific evidence has established that taking antioxidant supplements—including vitamins C and E, beta carotene, selenium and zinc—can help reduce the risk of chronic disease.

That being said, we know that antioxidant supplements (and supplements, in general) are not magic bullets, but they can be an important complement to a healthful diet.

If we twist science to create worldwide distrust in healthful dietary supplements, then we are truly harming consumers.

  1. Brody J. Potential for harm in dietary supplements. New York Times April 8th, 2008.
  2. Vitamin pills may do more harm than good. Scotsman UK. http://news.scotsman.com
  3. Why some popular pills might kill you. The Herald UK. http://www.theherald.co.uk
  4. G. Bjelakovic, D. Nikolova, L.L. Gluud, R.G. Simonetti, C. Gluud. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD007176.
  5. G. Bjelakovic, D. Nikolova, L.L. Gluud, R.G. Simonetti, C. Gluud. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 2007 Feb 28;297(8):842-57.
  6. Daniells S. The dangers of selective science. Nutraingredients.com April 12, 2008 [online news portal] http://www.nutraingredients.com
  7. Bjelakovic G and Gluud C. Surviving antioxidant supplements [editorial]. JNCI Journal of the National Cancer Institute 99(10):742-743, 2007.
  8. Bjelakovic G. Do antioxidant supplements work? Project Syndicate [online]. http://www.project-syndicate.org

 


Response to the Cochrane Database of Systematic Reviews 2008, Issue 2: "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases"

Our criticism of this report is similar to our criticism of a number of similar so-called studies. In each case, these reports were not actually studies, rather, they were meta analyses, which is to say, an analysis of other studies, which had previously been performed.

A meta analysis can provide valid data, but only if it is not subject to underlying bias. It appears there was an extreme degree of bias associated with this analysis. In particular, I would like to point out that the authors of the study chose to ignore 91% of available studies on the effects of vitamins on mortality. One reason for exclusion was because a study reported NO MORTALITY! By excluding all studies, which showed that vitamin supplementation had no effect on mortality, the authors immediately introduced an extreme degree of bias right from the beginning.

There was also no consistency in either the doses or the dosing schedule of the supplements examined in this study. For example, they looked at studies of vitamin A that varied from 1333 units all the way up to 200,000 units per day. This means is some these studies included doses too low to provide a meaningful effect or were so high as to almost guarantee toxicity. One of the studies included merely 1 individual.

Two thirds of the studies were performed on sick people, yet, the conclusions were that vitamins should not be taken by healthy people because they increase mortality

The study authors also made use of specific statistical techniques designed to produce their desired conclusions -namely, that vitamin supplements increased mortality. They were able to do this by combining studies that had widely varying doses of vitamins, or single or multiple vitamins and supplements and widely disparate numbers of test subjects. By utilizing what is called the "fixed effect" method of statistical analysis, they were able to demonstrate an increased mortality of 4 percent. The "random effect" model of statistical analysis would have been more relevant for study of this nature, but was not used.

We do not feel this study represented a significant advance in our knowledge about the effect of supplementation on mortality.

 


Response to the JAMA Report: "Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-analysis"

There are many conflicting reports on health products and their components. Based on extensive scientific research, Ray Kurzweil and Terry Grossman, M.D. continue to advocate antioxidants as an integral part of supplementation and disease prevention.

We believe that the conclusions drawn by the Journal of the American Medical Association report are misleading. The report was based on a meta-analysis of over five dozen studies, which had serious flaws:

  • Many of the studies cited lacked controls.
  • Studies varied widely in dosage.
  • Studies were of variable length – one lasted ONE DAY!
  • Many of the study participants were already sick and thus the studies are misleading with regard to disease prevention.
  • Other lifestyle factors – diet, exercise, and smoking were not considered.
  • Many of the studies used very low doses of these supplements.

As is pointed out in Fantastic Voyage, dosages need to be in therapeutic ranges (which are usually much higher than the out-of-date RDA's) in order for these nutrients to have a measurable effect. Among the 2,000 scientific citations in Fantastic Voyage are many that support the use of these and other nutritional supplements.

For more reading on the merits of vitamins and supplements:

  1. Summary and Abstract as published in the Cochrane Database of Systematic Reviews 2008, Issue 2: "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases":
    http://www.cochrane.org/reviews/en/ab007176.html
  2. Response by the Health Food Manufacturers Association, UK: HFMA Statement in Response to the Cochrane Review on Antioxidant Supplementation: http://www.responsesource.com/releases/rel_display.php?relid=38264&hilite=
  3. Rebuttal to the Recent Media Attack on Antioxidants—Life Extension Magazine:
    http://www.lef.org/featured-articles/consumer_alert_020307.htm
  4. Meta-analysis on Antioxidants Provides Muddled Conclusions—Body of Scientific Research Shows Antioxidants Provide Benefits for Maintaining Good Health—Statement by the Council for Responsible Nutrition: http://www.crnusa.org/PR07_JAMA_antioxidant_metaanalysis_022707.html
  5. Bad Medicine, Bad Reportage, or Both?—Alternative Medicine Review editorial by Kathleen Head, ND: http://www.thorne.com/altmedrev/.fulltext/11/2/83.pdf
  6. The WSJ's Fictitious "Case Against Vitamins"—Article by health and nutrition columnist Jean Carper: http://www.stopagingnow.com/pages/specialreport/wsj
  7. Is Vitamin E still safe?—Ray Kurzweil & Terry Grossman, M.D.:
    http://fantastic-voyage.net/ReaderQandA.htm#VitE
  8. Nutritionist Says Wall Street Journal Wrong on Vitamins—Posted by PR Newswire, 4/13/2006: http://www.enzymeexperts.com/world-enzymes/
    nutritionist-says-wall-street-journal-wrong-on-vitamins.html
0 Comments | Posted in Ray and Terry Research By Eric Huang

Research Blog - Prostate cancer & Vitamin Use

Monday, May 9, 2011 9:52:29 PM America/New_York

To put the results of this study in perspective, for every 10,000 men who took larger doses of supplements for 10 years there were 7 to 8 extra cases of fatal prostate cancer. This is less than 1 fatal case per 1,200 – 1,500 men per year year. Read More
0 Comments | Posted in Ray and Terry Research By Eric Huang

Research Blog - Human Growth Hormone

Monday, May 9, 2011 9:51:32 PM America/New_York

Current Thoughts on Hormone Replacement Part One: Human Growth Hormone, DHEA, Thyroid, Melatonin - Terry Grossman, M.D.

Introduction

It is widely believed that the modern era of anti aging medicine was born with the publication of “The Rudman Study” in 1990. In this placebo-controlled experiment, Daniel Rudman, M.D., from the Medical College of Wisconsin demonstrated that healthy, older men given daily injections of recombinant human growth hormone (rhGH) experienced a significant increase in lean body mass, bone density and skin thickness and a significant decrease in body fat.1 In an editorial accompanying this article in the same issue of the New England Journal of Medicine, Mary Lee Vance wrote that such studies regarding use of growth hormone in older adults “should be viewed as an important beginning.”2

Human Growth Hormone

I doubt that Dr. Vance realized how prescient she was back in 1990, since it is widely believed that the entire medical specialty of anti aging medicine was born after enthusiasm over the results of “The Rudman Study” on the benefits of growth hormone (GH) supplementation spread throughout the medical community. To many observers, it appeared that it was finally possible to reverse some of the effects of aging with a simple medical intervention – injection of recombinant human growth hormone. Rudman himself concluded, “The effects of six months of human growth hormone on lean body mass and adipose-tissue mass were equivalent in magnitude to the changes incurred during 10 to 20 years of aging.”3

Over the 15 years that have passed since publication of “The Rudman Study,” numerous writers in the lay press and medical community have hailed GH as the latest contender for the long sought “Fountain of Youth” title. Yet the waters of this fountain have become progressively muddied over the years. For example, while some additional studies have confirmed that rhGH injections can, in fact, help increase muscle mass and decrease fat mass, it appears that the increased muscle mass is merely cosmetic and that growth hormone-treated patients do not have increased muscle strength.4 Frisch found “no increase in maximal strength during concentric contraction of the biceps and quadriceps muscles, although levels of insulin-like growth factor-1 were doubled.”5 (Insulin-like growth factor-1 is the most commonly used blood test for assessing average GH blood levels.)

Growth hormone injections have been found to be beneficial in regard to a number of other markers associated with aging, Studies have demonstrated beneficial effects of GH supplementation on cardiovascular function, lipid levels and blood pressure.6,7 Osteoporotic women 68-75 years old given rhGH injections for one year had increases in radial bone mineral density of 8.1 percent and increased lumbar bone density of 3.8 percent.8 GH replacement can help patients with fatigue. In a placebo-controlled experiment of 20 patients disabled by Chronic Fatigue Syndrome, 40 percent of patients who received rhGH injections were able to return to work.9

Unfortunately, side effects are often experienced by patients who undergo rhGH injections. A 2002 National Institutes of Health study found that 24 percent of patients developed glucose intolerance or frank diabetes, 32 percent complained of carpal tunnel symptoms and 41 percent experienced arthralgias.10 Another study found that one-third of patients on hGH experienced side effects secondary to fluid retention, but that most of these disappeared spontaneously or responded to dose reduction. Cumulative dropout rates were 29% at one year and 38% at two years. Two-thirds of dropouts were because of lack of perceived benefit of the therapy.11

There is conflicting, but mostly reassuring, evidence regarding GH replacement and risk of malignancy. Bengtsson reported “in 289 hypopituitary patients on GH replacement, overall mortality and the rate of malignancies were similar to the normal population.”12

But some studies have shown small increases in colon cancer and Hodgkin’s lymphoma in individuals treated with GH.13

Of greater concern are animal experiments which suggest higher GH levels produce decreases in longevity. One study showed that transgenic mice specifically bred to over-express growth hormone experience a “drastically shortened life span” and experience symptoms of “accelerated aging.”14 Conversely, “hereditary dwarf mice deficient in GH, prolactin, and TSH live much longer than their normal siblings.”15 Since animal experiments suggest an inverse relationship between increased levels of growth hormone and longevity, it is prudent to question whether use of growth hormone therapy should be recommended as part of a serious longevity program. Long-term human experiments have yet to be conducted, but we do know that individuals with lifelong exposure to increased growth hormone levels (acromegalics) have decreased longevity.16

Because injectible GH has been available as a potential anti aging strategy in healthy adults for only a few years, we feel caution is the better part of valor at the present time. There are no results of any long-term studies on the safety of GH injections in healthy adults. Therefore, until more research is available, we recommend that GH injections be reserved for individuals who have documented growth hormone deficiency syndromes based on appropriate evaluation and testing, including IGF-1 level determinations and response to l-arginine or insulin challenges. rhGH injection therapy should not be routinely prescribed as a matter of course to “prevent aging” as promulgated by many anti aging clinics.

References:

  1. Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE. Effects of human growth hormone in men over 60 years old. N Engl J Med. 1990 Jul 5;323(1):1-6.
  2. Vance ML. Growth hormone for the elderly? N Engl J Med 1990 323: 52-54
  3. Rudman D et al. op. cit.
  4. Blackman MR, Sorkin JD, Munzer T, et al. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA 2002;288:2282-2292
  5. Frisch H. Growth hormone and body composition in athletes. J Endocrinol Invest. 1999;22(5 Suppl):106-9.
  6. Murray RD, Wieringa GE, Lissett CA, Darzy KH, Smethurst LE, Shalet SM. Low-dose GH replacement improves the adverse lipid profile associated with the adult GH deficiency syndrome.
    Clin Endocrinol (Oxf). 2002 Apr;56(4):525-32.
  7. Ahmad AM, Hopkins MT, Weston PJ, Fraser WD, Vora JP. Effects of GH replacement on 24-h ambulatory blood pressure and its circadian rhythm in adult GH deficiency. Clin Endocrinol (Oxf). 2002 Apr;56(4):431-7.
  8. Sugimoto T, Nakaoka D. Effect of recombinant human growth hormone in elderly osteoporotic women. Clin Endocrinol (Oxf). 1999 Dec;51(6):715-24.
  9. Moorkens G, Wynants H, Abs R. Effect of growth hormone treatment in patients with chronic fatigue syndrome: a preliminary study. Growth Horm IGF Res. 1998 Apr;8 Suppl B:131-3.
  10. Blackman MR, Sorkin JD, Munzer T, Bellantoni MF, Busby-Whitehead J, Stevens TE, Jayme J, O'Connor KG, Christmas C, Tobin JD, Stewart KJ, Cottrell E, St Clair C, Pabst KM, Harman SM. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial.
    JAMA. 2002 Nov 13;288(18):2282-92.
  11. Verhelst J, Abs R, Vandeweghe M, Mockel J, Legros JJ, Copinschi G, Mahler C, Velkeniers B, Vanhaelst L, Van Aelst A, De Rijdt D, Stevenaert A, Beckers A. Two years of replacement therapy in adults with growth hormone deficiency. Clin Endocrinol (Oxf). 1997 Oct;47(4):485-94.
  12. Svensson J, Bengtsson BA, Rosen T, Oden A, Johannsson G. Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J Clin Endocrinol Metab. 2004 Jul;89(7):3306-12.
  13. Sklar CA. Growth hormone treatment: cancer risk. Horm Res. 2004;62 Suppl 3:30-4.
  14. Bartke A. Can growth hormone (GH) accelerate aging? Evidence from GH-transgenic mice. Neuroendocrinology. 2003 Oct;78(4):210-6.
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  16. Orme SM, McNally RJ, Cartwright RA, Belchetz PE. Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab. 1998 Aug;83(8):2730-4.

0 Comments | Posted in Ray and Terry Research By Eric Huang

Research Blog - What is Longevity?

Monday, May 9, 2011 9:50:19 PM America/New_York

IMMORTALITY IS WITHIN OUR GRASP

Most of our conceptions of human life in the 21st century will be turned on their head. Not the least of these is the belief in the inevitability of death. As we succeed in understanding the genome and the proteome, many dramatic advances in treating disease and even reversing aging will emerge. The first two decades of the 21st century will be a golden era of biotechnology.

Many experts believe that within a decade we will be adding more than a year to human life expectancy every year. At that point, with each passing year, your remaining life expectancy will move further into the future. (Aubrey de Grey, longevity expert and gerontologist, believes that we will successfully stop aging in mice-who share 99 percent of our genetic code-within 10 years, and that human therapies to halt and reverse aging will follow 5 to 10 years after that.) A small minority of older boomers will make it past this impending critical threshold. You can be among them.

As interesting as the first two decades of this century are likely to be, subsequent decades should lead to even more dramatic changes. The result will be profound differences in every facet of our lives, from our health and longevity to our economy and society, even our concepts of who we are and what it means to be human. Within a couple of decades we will have the knowledge to revitalize our health, expand our experiences-such as full-immersion virtual reality incorporating all of the senses, augmented reality, and enhanced human intelligence and capability-and expand our horizons.

As we peer even further into the 21st century, nanotechnology will enable us to rebuild and extend our bodies and brains and create virtually any product from mere information, resulting in remarkable gains in prosperity. We will develop means to vastly expand our physical and mental capabilities by directly interfacing our biological systems with human-created technology.

Although human ability to take command of the course of life and death is controversial, we believe that the ability to broaden our horizons is a unique and desirable attribute of our species. And we certainly believe that it is worth the effort to remain healthy and vital today to experience this remarkable century ahead.

Aubrey de Grey uses the metaphor of maintaining a house to explain this key concept. How long does a house last? The answer obviously depends on how well you take care of it. If you do nothing, the roof will spring a leak before long, water and the elements will invade, and eventually the house will disintegrate. But if you proactively take care of the structure, repair all damage, confront all dangers, and rebuild or renovate parts from time to time using new materials and technologies, the life of the house can essentially be extended without limit.

The same holds true for our bodies and brains. The only difference is that while we fully understand the methods underlying the maintenance of a house, we do not yet fully understand all of the biological principles of life. But with our rapidly increasing comprehension of the human genome, the proteins expressed by the genome (proteome), and the biochemical processes and pathways of our metabolism, we are quickly gaining that knowledge. We are beginning to understand aging, not as a single inexorable progression but as a group of related biological processes.

Strategies for reversing each of these aging progressions using different combinations of biotechnology techniques are emerging. Many scientists, including Ray Kurzweil and Terry Grossman, M.D, believe that we will have the means to stop and even reverse aging within the next two decades. In the meantime, we can slow each aging process to a crawl.

The goal of extending longevity can be taken in three steps, or Bridges. Transcend is intended to serve as a guide to living long enough in good health and spirits (Bridge One) to take advantage of the full development of the biotechnology revolution (Bridge Two). This, in turn, will lead to the nanotechnology-AI (artificial intelligence) revolution (Bridge Three) which has the potential to allow us to live indefinitely.

The knowledge of how to maintain our biological "house" and extend its longevity and vitality without limit is close at hand. Ray & Terry's Longevity Program can help you implement the extensive knowledge that we do have today to remain healthy as the reverse engineering (decoding and understanding the principal methods) of our biology proceeds.

1 Comments | Posted in Ray and Terry Research By Eric Huang