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Life Extension Magazine

LE Magazine Special Edition, Winter 2004/2005
Life Extension Funds Research To Combat Aging & Death

The healthy human life span will be extended radically in the 21st century. It’s only a matter of when this will happen, not if it will happen. The Life Extension Foundation (LEF) is doing everything in its power to enable this revolutionary breakthrough to occur sooner rather than later.

Picture this. You are old, have Parkinson’s disease, a malfunctioning kidney, and are becoming increasingly disabled. Your remaining years are passing by faster and faster. Your quality of life is diminishing rapidly. You live more in the past than in the future. You are becoming anxious and depressed. Life just isn’t as good as it used to be.

You enter a rejuvenation center. Young substantia nigra cells are injected into the basal ganglia area of your brain to cure your Parkinson’s disease. Young hippocampal cells are injected into your brain to improve your memory. Young cells are injected into the hypothalamus in your brain to rejuvenate your hormonal system. And young dividing cells are injected into your body to rejuvenate your skin, glands, and other tissues. Finally, you receive a kidney transplant, precisely matched to your tissue type and size to vastly improve your kidney function. All these tissues have come from a regional tissue bank, where they had been stored at super-cold temperatures, after undergoing a process called vitrification.

When you leave the rejuvenation center, you have a new lease on life. You are younger and healthier. You feel much better. There’s a spring to your step that you haven’t felt in decades. The future looks brighter. Your libido is heightened more than ever before. You even start thinking of having children again. But first you want your wife to go to the rejuvenation center so she can look and feel as well as you do. Life has never been better.

TOOLS OF THE TRADE

One reason we now have a realistic chance of conquering aging and death is the availability of highly-sophisticated equipment that enables scientists to probe the secrets of life more effectively than ever before. Here are some equipment acquisitions by both labs discussed in this article, which are (or will be) helping their scientists to conduct research.

The 2100 Bioanalyzer from Agilent: An instrument that uses lab-on-a-chip technology to provide improved analysis of DNA, RNA, proteins and cells. The cost will be $29,800.

The Veritas Automated Laser Capture Microdissection System from Arcturus: An advanced instrument that enables scientists to obtain precise isolation of homogenous cell populations from tissues. A laser attached to a microscope is used to cut the cells one wishes to study in a non-contact, contamination-free setting under microscopic visualization. This state-of-the-art system will provide extraordinary power to discover biomarkers of aging and killer diseases in the cells of liver, brain, and other tissues. The cost will be $184,500, which will be paid for at the rate of $20,000 per month.

NanoDrop ND-1000A Spectrophotometer: Provides scientists with highly accurate analyses of extremely small samples with remarkable reproducibility. The sample retention system eliminates the need for cuvettes and capillaries, which decreases the measurement cycle time. In addition, the high absorbance capability eliminates the need for most dilutions. One can make fewer dilutions and take more readings. The cost was $7,500.

Cryostat HM550: The unit enables sample section thickness from 1 to 100µm; trim section thickness from 5 to 500µm. LC display shows relevant data such as set, actual temperature, section sum, remaining travel, number of sections and time, trim and fine section thicknesses, retraction function. Temperature of the cryo chamber can be controlled from 0 to -35°C, which permits samples to remain at the desired temperature. The cost was $22,000.

Eppendorf Centrifuge: This multipurpose
centrifuge features powerful, maintenance-free motors. It accommodates a variety of rotors for unparalleled application versatility with temperature range from –9°C to 40°C. There are three centrifuges in one: a high capacity general purpose centrifuge for cell harvesting; a high-speed centrifuge for separating cell lysates; and a micro centrifuge for DNA precipitations. The cost for the centrifuge and various rotors will be $12,000.

21st Century Medicine
Ciphergen Proteomics Workstation: Measures protein levels indicative of treatment effects to help understand the mechanisms of biological injury and protection. The cost was $160,000.

Neurophysiology Workstation: Includes many pieces of equipment that collectively allows scientists to evaluate the functional integrity of brain tissue in great depth. The cost was $550,000.

Cryoprotection Perfusion Apparatus: Allows two different organs to be perfused with vitrifiable concentrations of cryoprotectants at the same time using different perfusates and different perfusion protocols. Invented and constructed by 21CM. The cost was $150,000.

Shimadzu High Performance Liquid Chromatography System: Allows identification and purification of biological molecules, including proteins, as well as cryoprotective agents, and perfusate components. The cost was $55,000.

Philips Electron Microscope (used) and Haskris RO75 Chiller: Allows examination of biological tissues at magnifications approaching molecular level. It was obtained free-of-charge. It has taken about $10,000 to make it work. A new electron microscope would cost up to $100,000.

Genes That Cause Aging or Promote Longevity
To develop the kind of anti-aging therapies described on the previous page, Life Extension is on a mission to find out which genes cause aging and which genes promote longevity. Once these goals are achieved, Life Extension will be able to discover nutrients and drugs that can slow aging and extend the healthy life span. We will also be able to pinpoint the cells that cause the ravages of aging, which will enable us to engineer young cells to replace them. Eventually, we will be able to engineer critical cells at the DNA level, which, after being introduced into our bodies, will reprogram us to remain young and healthy indefinitely.

Life Extension has poured millions of dollars into research aimed at finding authentic anti-aging therapies. We have funded life span studies at the University of Wisconsin, the University of California at Riverside, and the University of Arkansas. We’ve funded gene transfer studies at the Gerontology Research Center in Baltimore, neurotransmitter studies to find the key to brain aging at the University of California at Berkeley, and nuclear enzyme studies at Mt. Sinai Medical Center in New York.

Over the past few years, Life Extension-funded scientists have been using micro-arrays (gene chips) to measure the expression of thousands of genes at a time in normally aging animals and in models of extended life span. Thus far, this research has used two models of extended life span: caloric restriction, which has been shown to radically extend life span in mice, rats, dogs, and other species since the 1930s; and Ames dwarf mice, which have a gene mutation that interferes with their ability to produce pituitary hormones. Ames dwarf mice have been shown to live 50% longer than normal mice.

Possible Anti-Aging Therapies
The gene-chip research the Life Extension Foundation is funding is now being conducted at a laboratory (BioMarker Pharmaceuticals) in Northern California. By comparing gene expression profiles in mice with extended life spans with those of mice who age normally, Dr. Joseph Dhabbi has identified genes associated with aging and longevity.1,2 The use of this type of comparative analysis has enabled Dr. Dhabbi and his colleagues to find at least one possible anti-aging therapy: metformin,3 which has been prescribed for years for diabetes, and which is similar to another drug (phenformin), which extended the life span of mice in a study in Russia in 1980.4

BioMarker is currently looking at the effects of metformin on life span in mice and collaborating with Dr. Andrzej Bartke of Southern Illinois University, who has been studying long-lived Ames dwarf mice, to identify genetic pathways, such as the insulin and IGF-1 (Insulin Growth Factor) pathways, which may confer longevity by bolstering resistance to stress, enhancing immune function, and altering programmed aging.5 They have also discovered, for the first time, that caloric restriction can extend life span in old mice, perhaps by rejuvenating the mice, which is good news for those of us middle age or older.6

LEF-funded researchers are now preparing to do new gene chip studies to evaluate the anti-aging properties of resveratrol, a grape extract that has been shown to produce many health benefits in animals and humans.

Rejuvenation and the Cure of Killer Diseases
Transplantation is currently a small field. In the future, transplantation will become the dominant field in the rejuvenation of aging people and the cure of patients with deadly diseases such as cancer, heart disease, stroke, diabetes, Parkinson’s, and Alzheimer’s disease.

In addition to the transplantation of cells, tissues, organs, and other body parts from human donors, a wide array of laboratory grown natural and bioartificial tissues will be developed to expand the field of transplantation. Also available will be tissues from animals such as pigs and non-human primates, as the field of xenotransplantation matures. Laboratory grown cells and organs will include simple replacements for aging, injured, or diseased body parts in humans, and genetically and immunologically engineered tissues to improve upon natural body parts.

Such therapies will emerge as longevity genes (and the physiologic systems they control) are identified, and as stem cell research advances to the point where virtually any type of young specialized cells and organs can be manufactured in the laboratory. Billions of dollars are being spent to conduct research in these fields in universities, medical centers, and private laboratories around the world. This research is already starting to pay off. Before long, it will lead to an explosion in new therapies to extend the healthy human life span.

Life Extension Funds the Key to Rejuvenation Medicine
All the cells, tissues, organs, and other body parts—from whatever source—which will fuel the upcoming transplantation revolution have one thing in common: they need to be cryopreserved effectively for optimal use. Tissue and organ banks will enable doctors throughout the world to have fingertip access to the best tissues needed for each individual patient. It will permit rapid transplantation of compatible tissues for patients who have had a heart attack, stroke, or serious accident. It will permit the development of transplantable tissues specially engineered for individuals who suffer from the ravages of aging and chronic diseases such as Parkinson’s or Alzheimer’s disease. It will, eventually, enable doctors to cure or repair almost any patient.

Life Extension has been spending millions of dollars to fund the only research in the world aimed at developing methods to successfully cryopreserve complex biological systems, including organs such as corneas, kidneys, and brains. This research is being conducted at a laboratory in Southern California (21st Century Medicine). The lab’s Chief Scientific Officer, Gregory M. Fahy, Ph.D., is the pioneer in the development of vitrification, a special method of cryopreservation that avoids the formation of ice crystals (the major cause of damage in frozen tissues).7 21st Century Medicine’s vitrification methods are the most advanced in the world, in large part because of the extraordinary expertise of Dr. Fahy, and in part because of another of its scientists, Brian Wowk, Ph.D, who has pioneered the discovery and development of ice-blockers that improve the vitrification process.

Recent advances in this laboratory include the cooling of rabbit kidneys to -45o C, with subsequent survival and good function after transplantation (after rewarming) of eight out of eight kidneys.8 This is by far the greatest advance in major organ cryopreservation, after decades of efforts in many laboratories around the world. Dr. Fahy’s research team is currently working to extend this success to kidneys cooled to as low as -150o C, which is cold enough to arrest biological changes for unlimited periods of time.

The lab has successfully vitrified corneas in both rabbits and humans and has successfully transplanted human corneas into rabbits. Negotiations are underway with doctors in China to conduct clinical transplant trials in humans with 21st Century Medicine’s vitrified corneas.

21st Century Medicine was recently awarded a $900,000 grant by the National Heart, Lung, and Blood Institute to pursue improvements in the hypothermic preservation of hearts. This research should eventually help to improve the transplantation of human hearts.

The lab is also in the early stages of a major project to vitrify rabbit brains. Studies have shown that entire brains can be vitrified with little apparent structural damage, and that brain slices can survive after vitrification and rewarming and can even produce electrical activity after exposure to vitrifiable solutions. The potential of this research project goes from providing neurobiologists with well-preserved brain tissue for research to the development of suspended animation in humans, which would enable people to escape death, even if they are dying years before rejuvenation therapies are available.

Life Extension is the foremost source of advanced dietary supplements to help our members maximize their current life span potential. These products are based upon research from laboratories around the world, including our own in-house research. Members can be assured that the Life Extension Foundation is doing everything it can to help them live longer now, while using product sales and membership dues to fund path-breaking research that will lead to radical breakthroughs in the control of aging and death.

Research

1. Cao SX, Dhahbi JM, Mote PL, Spindler, SR. Genomic Profiling of Short- and Long-Term Calorie Restriction in the Liver of Aging Mice. Proc. Natl. Acad. Sci. U.S.A 2001;98:10630-10635.

3. Spindler SR, Dhahbi JM, Mote PL, Kim HJ, Tsuchiya T. (2003) Rapid Identification of Candidate CR Mimetics Using Microarrays. Presented at The International Association of Biomedical Gerontology, 10th Congress, Strategies for Engineered Negligible Senescence: Reasons Why Genuine Control of Aging may be Foreseeable, Queens’ College, Cambridge, England, 19-23 September 2003.

4. Dilman VM, Anisimov, VN. Effect of treatment with phenformin, diphenylhydantoin or L-dopa on life span and tumour incidence in C3H/Sn mice. Gerontology. 1980;26(5):241-6.

5. Tsuchiya T, Dhahbi JM, Cui X, et al. Additive Regulation of Hepatic Gene Expression by Dwarfism and Caloric Restriction. Physiol Genomics. 2004;17:307-15.

6. Dhahbi JM, Kim HJ, Mote PL, et al. Temporal linkage between the phenotypic and genomic responses to caloric restriction. Proc Natl Acad Sci U S A. 2004;101(15): 5524-9.

7. Pegg, DE. Ice crystals in tissues and organs. In: Pegg DE,. Karow Jr. AM Eds. The Biophysics of Organ Cryopreservation. New York, NY: Plenum Press; 1987:117-140.

8. Fahy, GM, Wowk, B, Wu, J, et al. Cryopreservation of organs by vitrification: perspectives and recent advances. Cryobiology 2004;48:157-78.