The Critical Mission of Life Extension Foundation®
Since its inception in 1977, the Life Extension Foundation (LEF) has conducted scientific research that goes beyond the scope of academic institutions and biomedical companies. The purpose of this research is to identify and validate technologies that can delay/reverse aging and prevent premature death.
Mainstream research today is focused on how to treat heart attacks, cancer, Alzheimer's disease and strokes. These are the diseases that we generally assume cause death.
What most doctors don't yet recognize is that these devastating illnesses are caused mostly by aging. The Life Extension Foundation has provided more than $140 million to scientists across the country to look beyond the disease state and instead search for authentic anti-aging and anti-death solutions. Our objective is to prevent or postpone age-related disease, restore health, and provide much longer and higher-quality human life spans.
This annual report will inform you about the research programs we are funding and detail LEF's commitment to meaningful scientific discovery.
It outlines how Life Extension continues to fund targeted research into killer diseases such as cancer, cardiovascular disorders, immune dysfunction and neurological deficits. These programs are part of a strategic vision to limit or prevent diseases as we mature.
LEF funds researchers denied by governments
As described in the January 2014 issue of Life Extension Magazine®, the Life Extension Foundation has been funding many researchers who have been denied funding by the federal government. In 2013 the most spectacular example of success by these researchers was the study of naked mole rats by Andrei Seluanov and Vera Gorbunova, who are a husband and wife team at the University of Rochester in Rochester, New York. Dr. Seluanov has the second largest naked mole rat colony in the world. Naked mole rats are about the same size as mice, but live about ten times longer. The two scientists found that naked mole rat cells stop growing when the cells start to crowd each other.
Cancer is uncontrolled growth of cells, which can quickly lead to crowding of cells ― something naked mole rats prevent. The two scientists found that naked mole rat cells stop growing when the cells start to crowd each other. Cancer is uncontrolled growth of cells, which can quickly lead to crowding of cells - something naked mole rats prevent.
Dr. Gorbunova reported that she and her husband later discovered that naked mole rats secrete a form of hyaluronic acid that is five times larger than what human or mouse cells secrete. When the hyaluronic acid was removed from the naked mole rat cells, they became as vulnerable to cancer as mouse cells. That discovery was reported in the July 18, 2013 issue of the journal NATURE as a cover story. Thanks to funding from the Life Extension Foundation, the couple then discovered that naked mole rat protein synthesis is exceedingly error-free. Both of those discoveries caused the journal SCIENCE to name the naked mole rat the 2013 "Vertebrate of the Year."
The research of Dr. Gorbunova is concerned with how DNA damage and repair contribute to aging and cancer. DNA damage often leads to mutation and cancer, but DNA damage may also contribute to aging. She is hopeful that what she can learn about what causes DNA damage and what she can learn about facilitating repair of DNA damage can lead to a reduction of aging and cancer in humans. There has been much interest among life extensionists in resveratrol, a substance found on the skin of red grapes which some scientists believe has been shown to extend the life span of nematode worms. It was proposed that the ability of resveratrol to activate sirtuin activity is the basis of the benefits of resveratrol. There are seven sirtuins in mammals, numbered SIRT1 to SIRT7. The sirtuin in mammals that is activated by resveratrol is SIRT1. Resveratrol has been shown to protect obese mice from diabetes. SIRT6, on the other hand, is able to protect normal mice from DNA damage, and SIRT6 promotes repair of DNA damage. SIRT6 activity increases the DNA repair mechanisms for double-strand breaks. DNA double-strand breaks are dangerous. DNA lesions that can cause cell death or genomic rearrangements are frequently found in aged and cancerous cells. Activation of the SIRT6 gene in mice has been shown to extend their life span. Some rodents have a more effective SIRT6 gene than other rodents, so Dr. Gorbunova is seeking to understand the difference. Dr. Gorbunova is looking for chemicals that activate SIRT6 much as resveratrol is thought to activate SIRT.
Robert Shmookler Reis, Ph.D., who is a professor at the University of Arkansas for Medical Sciences, Little Rock, Arkansas is another researcher who is being funded by the Life Extension Foundation after having been denied funding by the US federal government. His research career has been focused on the influence of genetics on longevity and the diseases of aging. Two decades after it was discovered that a genetic alteration could double the life span of the nematode worm, Dr. Reis was able to achieve a ten-fold increase in nematode life span.13 Humans who live over age 100 have been found to possess a similar gene alteration.14 With funding from the Life Extension Foundation he is hoping to find drugs that can produce similar disease-prevention and life-extending benefits.
João Pedro de Magalhães, Ph.D., is yet another researcher studying genetics for answer to questions concerning extending human health and longevity, but who was unable to do so with government support. Dr. de Magalhães is a Senior Lecturer (equivalent to an Associate Professor in the US) at the University of Liverpool, Liverpool, United Kingdom. Dr. de Magalhães is interested in the fact that the bowhead whale has not only been estimated to live over 200 years, but is able to remain disease-free until much more advanced ages than humans can.15 The mechanisms for the longevity and resistance to aging-related diseases of bowhead whales are unknown, but they must possess aging prevention mechanisms. In particular in the context of cancer, bowhead whales must have anti-tumor mechanisms, because given their large size and longevity their cells must have a massively lower chance of developing into cancer when compared to human cells.16 The Life Extension Foundation has provided funding for sequencing the genome of the bowhead whale. Understanding the bowhead whale's exceptional longevity and resistance to diseases could lead to techniques to improve human health and longevity.
LEF funds researchers previously funded by the Ellison Medical Foundation
As described in the September 2011 issue of Life Extension Magazine, the Ellison Medical Foundation (created by software billionaire Larry Ellison) has spent hundreds of millions of dollars funding fundamental research on the biology of aging since 1998. Early in the fall of 2013, the Ellison Medical Foundation announced that this program is being discontinued. No reason has been given. The Life Extension Foundation is now funding three researchers who were previously being funded by the Ellison Medical Foundation.
Howard Chang, MD, PhD is an Associate Professor of Dermatology at Stanford University School of Medicine, Palo Alto, California. Dr. Chang believes that epigenetic (gene expression) changes in stem cells can be made that can reverse aging. Nearly all tissues in the body contain stem cells, which continually maintain tissue function. With age, however, stem cell function declines, causing a decline in tissue function. Dr. Chang has currently succeeded in measuring the gene expression of adult stem cells. He seeks to determine how gene expression changes with age, and then find drugs to reverse those changes. The resulting rejuvenation of tissues should reduce aging-associated diseases and help rejuvenate people for extended youth, health and longevity.
James Shorter, Ph.D., is an associate professor of Biochemistry and Biophysics at the School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania. Dr. Shorter has discovered that various heat shock proteins can prevent or reverse the kind of protein aggregation that leads to Alzheimer's disease, Parkinson's disease, Huntington's disease, and other aging-associated protein aggregation diseases. With funding from the Life Extension Foundation he has been finding or modifying heat shock proteins that are increasingly better able to reverse the amyloid-beta protein aggregation that occurs in Alzheimer's disease. He hopes to apply similar techniques to reverse the other protein that aggregates in Alzheimer’s disease, namely tau protein.
Victoria Belancio, Ph.D., is an assistant professor of Structural and Cellular Biology at Tulane School of Medicine in New Orleans, Louisiana. With funding from the Life Extension Foundation, Dr. Belancio has been studying the molecular biology of transposable elements ("jumping genes"). She has determined that the expression (and damage) of these elements is influenced by the host’s exposure to environmental light in an animal model of human cancer, a concept that has not been previously considered. She wants to determine whether the damage induced by these elements contributes to aging and age-associated diseases, such as cancer. She has also been studying how different light intensities at night influence DNA damage from these elements in rats. By learning how disturbances in circadian rhythm (such as is experienced by shift workers and world travelers) lead to genetic instability, cancer, and aging, Dr. Belancio hopes to demonstrate how intervention can mitigate the negative effects.
Accelerating stem cell research
The Life Extension Foundation is helping to fund the development of stem cell technologies designed to eliminate atherosclerosis, which will prevent many premature deaths caused by occlusive arterial disease (coronary atherosclerosis and ischemic stroke).
Pluripotent stem cells (cells capable of creating any type of cell) will be used to differentiate into endothelial progenitor cells that will replace the aged, damaged, and plaque-laden cells on the walls of blood vessels. These new cells will not only be young, but may remain young indefinitely by the use of the telomere-lengthening enzyme telomerase.
When perfected, this technology may enable doctors to inject progenitor cells that will regenerate every tissue in the body, thus restoring aging humans to youthful health and vigor.
The Life Extension Foundation is also providing funding to create and differentiate pluripotent stem cells into immune system cells that could treat patients afflicted with certain cancers and HIV. This technology has the potential to rejuvenate everyone’s immune system.
A grant was made in January 2013 to fund research into developing immune system blood stem cells (hematopoetic stem cells or HSCs) from undifferentiated stem cells. The primary challenge of this project will be to make undifferentiated stem cells develop into the specific HSC stem cell type. Once that objective has been achieved, the second objective will be to get the HSCs to multiply into large numbers of HSCs.
If this research project succeeds, the most immediate benefit will be the ability to extract cells from patients with compromised immune systems (such as patients with cancer), induce those cells to become undifferentiated stem cells, re-differentiate those cells into HSCs, expand the HSCs to become plentiful, and then administer the plentiful HSCs to patients from whom the original cells were taken —without fear of immune system rejection.
This stem cell therapy is designed to regenerate/rejuvenate tissues that have been damaged or become senescent. The advantage of using stem cells derived from the patient’s own tissue is that they will not be rejected due to immune system incompatibility (as would happen if the cells were derived from another person).
The success of this project has the potential to not only benefit patients suffering from HIV and immune system cancers, but to rejuvenate the immune systems of the elderly. Because of immune system aging, a person over age 65 is about a hundred times more likely to die from an influenza-related death than a person who is between the ages of 5 and 49.
Finding a way to live beyond 100 years in good health
Super-centenarians are people who live 110 years and beyond, usually in relatively good health. They appear to have better genes than the rest of us, and understanding the differences could be the key to allowing anyone to reach those ages.
The Life Extension Foundation is funding a project by James Clement and Parijata Mackey to travel in the USA and abroad collecting DNA samples from people who have lived longer than 105 years. Their goal is to determine what is genetically different about these very long-lived individuals that allowed many of them to live extremely long lives without cancer, diabetes, cardiovascular diseases, or Alzheimer’s.
James Clement and Parijata Mackey are working with Dr. George Church of Harvard Medical School to sequence and analyze the whole genomes of these “super-centenarians” in the hope of discovering what genes confer such health and longevity. The goal of cataloging this knowledge is to help find ways to bring such health and longevity benefits to everyone – so we can all become super-centenarians.
Rejuvenation of Old Worms
Dr. Cynthia Kenyon is a Distinguished Professor of Biochemistry and Biophysics at the University of California who achieved world fame in 1993 when she doubled the life span of nematode worms by means of a single mutation. Recently she has discovered indications that certain worm mutations under some conditions will allow worms to become younger. In mid-2012 LEF made a grant to Dr. Kenyon to investigate these mechanisms with the hope of rejuvenating old worms. If this works, it could potentially make old people young again.
Every day in 2013, 1,600 Americans died of cancer, victims, to a great extent, of the antiquated but entrenched treatment system that relies on chemotherapy, radiation and surgery. Millions more are still alive, but survive with long-term treatment side effects, shortened life spans, and the omnipresent prospect of a cancer recurrence. Our war on cancer is just beginning.
In our quest to gain complete control over human aging, Life Extension Foundation is committed to reducing these appalling deaths from malignancies. Our support of innovative cancer research is one critical means to this end.
This cancer research progress report, authored by Orn Adalsteinsson, Ph.D., describes highlights of the Life Extension Foundation's various cancer research initiatives over the past year.
Laser Assisted Immunotherapy
LIT, or laser immunotherapy, uses a combination of local laser irradiation and local administration of GC, or glycated chitosan, at either primary or metastatic tumor site which creates a synergistic photothermal and immunological effect. The GC, which is given by intratumoral injection after laser irradiation of the tumor lesions, exerts an immunoadjuvant effect on metastatic cancers.
During laser irradiation, the treated lesion can reach temperatures of 60–70°C.
The irradiated tumor cells swell and break into pieces, creating antigen sources which when combined with GC stimulates the host immune system to generate tumor-specific immune responses. GC is a unique adjuvant class of natural polysaccharides, or a compound that stimulates the immune system and increases the response to a vaccine, without having any specific antigenic effect of its own. GC has been found to enhance both humoral and cell-mediated immune responses.
Interestingly, GC can directly activate dendritic cells (DC), and enhance antigen presentation to DCs, causing proliferation of T cells. The combined thermal treatment and GC stimulation can achieve even higher levels of T cell proliferation which in short upregulates the immune system surveillance.
The key aspect of this approach is that the stimulated immune system attacks not only the primary tumor, but also metastases located anywhere in the body. Because those metastases often bear the same abnormal signal proteins as the primary tumor, they now essentially are marked for the body's natural defense mechanism to seek out and destroy - no matter where they've moved to in the body.
As an added bonus, the immune system "remembers" the identifying markers of the cancer and continuously maintains surveillance to prevent future recurrence. In essence, laser-assisted immunotherapy creates a tiny "vaccine factory" within the victim's body that throws the entire immune system's resources at precisely that person's own tumor.
When compared to existing treatments, which can be a dangerous mix of chemotherapy, radiation, and surgery - which many times do not cure the cancer, but can destroy an individual's remaining quality of life - LIT is a superior treatment option.
While the initial LIT study has been completed for several years, we continue to follow the trial participants. Of the 15 subjects we reported on last year, 80% remain alive at over four years post-study. Furthermore, 6 of the 15 woman treated are disease free. Of the 15 women, 9 were stage IV or metastatic and 5 of these women are currently disease free. Compared to the typical United States survival rate for women with advanced breast cancer which is 23.8% at 5 years, the results of the LIT study are remarkable.
The Life Extension Foundation is continuing its support for additional laser immunotherapy techniques which allow for even broader applications than we have seen in the breast cancer trials.