The Principal Mission of Life Extension®
Since its inception in 1980, Life Extension (LE) 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. Life Extension has provided more than $175 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 LE’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.
LE funds researchers denied funding by governments
As described in the January 2014 and May 2015 issues of Life Extension Magazine®, Life Extension has been funding
many researchers who have been denied funding by the federal government. The following research teams have received support from Life Extension:
Vera Gorbunova, Ph.D.,
and Andrei Seluanov, Ph.D., are wife-and-husband professors at the University of Rochester in the state of New York. The couple's research
has been funded by Life Extension (profiled in the May 2015 issue of Life Extension Magazine®). Dr. Seluanov has the second-largest naked mole rat
colony in the world, which he was in danger of losing had it not been for Life Extension funding. Naked mole rats are about the size of mice, but live at
least ten times longer than mice, without evidence of aging1 or cancer.2 Dr. João Pedro de Megalhães from the University of Liverpool, UK, attempted to analyze the naked mole rat
genome with the couple, but could not find genes which explained either the longevity or the cancer-resistance.3 The discovery by Dr. Seluanov
and Dr. Gorbunova that a large molecular weight hyaluronic acid secreted by the naked mole rats protects the mole rats from cancer, led to a cover story in
the prestigious journal NATURE.4 Their subsequent discovery of exceedingly error-free protein synthesis by the naked mole rat5 caused the journal SCIENCE to name the naked mole rat "Vertebrate of the Year" for 2013.6 Precision protein synthesis by
naked mole rats contributes to both their cancer-resistance and longevity. The next year the couple co-authored a review of cancer resistance and longevity
in many species that was the cover story of the August 2014 issue of NATURE REVIEWS: GENETICS.7 More recently, the couple has compared
the genomes of mice, naked mole rats, and humans, finding support for the idea that genome maintenance (DNA repair) is important for longevity and
cancer-resistance.8 Dr. Gorbunova has particular expertise in DNA repair. She discovered that the sirtuin SIRT6 more than triples repair of DNA
damage.9 With Life Extension funding, she has been searching for molecules which will stimulate SIRT6 activity.
Dr. George Church, Harvard Medical School geneticist, was featured in the May 2013 issue of Life Extension Magazine. This article reported on how the Life Extension Foundation was funding the collection and analysis of genes of supercentenarians (people living to age 110 or older) to discover protective genes that allow them to live so long. This funding was provided to a group called Androcyte LLC that initially consisted of CEO James Clement and his assistant, Parijata Mackey. They traveled the world to collect tissue samples from approximately 60 supercentenarians and their family members. Dr. Church was collaborating with Androcyte to analyze the genes.
Since then, Dr. Church has achieved additional fame as being a co-inventor and pioneer in the new CRISPR gene-editing technology. Also since then, the Life Extension Foundation continued to fund Androcyte to open a laboratory in California dedicated to applying CRISPR to deliver longevity genes, initially to mice. Androcyte CEO James Clement continues to work with Dr. Church in doing this research.
Androcyte currently has a colony of 300 mice, and growing. Sixty of these mice were received from the National Institutes of Aging and are between 26 and 36 months of age—the equivalent of very old humans. Androcyte has targeted about 25 promising longevity genes, which are being tested in the mice via CRISPR/Cas9 gene therapy. Particular attention is being paid to the elderly mice to see if they can be restored to youth and good health. To keep costs low, Androcyte purchased a one-acre property with an existing 1,500 square foot building which is an hour’s drive from Los Angeles. As it outgrew its initial vivarium (housing for mice), it added two office trailers to the property to provide additional vivarium and laboratory space.
In addition to Dr. Church and other expert consultants, Androcyte CEO James Clement has acquired the assistance of two new interns: Ellie Dubrovina and David Falzarao, who were referred by Aubrey de Grey’s SENS Foundation. Ellie assists with the scientific work, whereas David assists with the care of the mice.
Androcyte has also received two elderly Arabian mares 28 and 30 years old (age-equivalent to 80-year-old humans) from a sanctuary. If genes delivered by CRISPR to the mice are able to restore youth and health, CRISPR delivery of those genes will be tested on the horses to show that large animals can also benefit. Success with the horses could pave the way for using CRISPR to bring better health and greater longevity to humans.
Victoria Belancio, Ph.D.,
is an assistant professor at Tulane Medical School who has been using Life Extension funding to study the molecular biology of retrotransposons ("jumping genes") in chromosomes, and the resulting genomic instability.10 She has determined that increased
retrotransposon activity results from light-at-night (often due to shift work) which can cause aging11 and cancer.12,13 She has
determined that light-at-night, retrotransposon genetic instability, and melatonin inhibition of retrotransposon activity are relevant for breast cancer
risk and breast cancer resistance.13-15 Aside from demonstrating the use of melatonin to inhibit the genetic instability due to
retrotransposons, Dr. Belancio has found that an antibody can also be used to reduce retrotransposon-induced genetic instability.16
A startup company that Life Extension has been funding is Advanced Neural Biosciences (ANB). ANB has been studying the mechanisms of
damage that occurs to blood circulation in the brain in conditions such as stroke, with the aim of reducing those effects. ANB has developed a mathematical
formula that can predict the amount of blood-flow impairment resulting from stroke-like states based on electron micrograph images of the brain. ANB
reported that in 2015 the company has developed compounds that can restore brain blood flow after two hours without blood flow. Normally, shorter periods
of time without blood flow in the brain prevents any subsequent blood flow.
In 2015, Advanced Neural Biosciences started a comprehensive screening program to identify cryoprotectants that can inhibit ice formation in the brain without causing extreme brain shrinking (as existing vitrification solutions do). They have identified a number of promising directions and have devoted most of their efforts in 2016 to validate a number of these vitrification solutions in an in-situ brain cryopreservation model. This is a very promising discovery in the field of neural cryobiology and most of ANB's efforts will be aimed at further validating the glass-forming and toxicity properties of these agents.
In collaboration with a prominent deep learning researcher at the University of Chicago, and Michael Perry, Ph.D. at the Alcor Life Extension Foundation, ANB has developed a computer algorithm that can be used to infer the duration of cerebral ischemia from a set of electron micrographs. They have completed a first draft of a paper that characterizes the histological changes at various durations of cold and normothermic ischemia, which will also include this pioneering application of deep learning in histology. This paper will be submitted for peer review in 2016 and submitted to a critical care medicine journal.
In collaboration with the Alcor Life Extension Foundation, ANB has completed a comprehensive research project to understand the effects of different classes of medications on the perfusion of the ischemic brain. They have identified a number of specific medications that allow ice-free cryopreservation of the brain up to 2.5 hours of normothermic ischemia if administered prior to the insult, and have also investigated the limits of this approach when these medications are administered after the ischemic insult.
In 2015, ANB's lab signed a 5-year lease to conduct research at a stand-alone facility in NE Portland. This additional lab space and lease security allows them to conduct more research models simultaneously and enhance their current capabilities. In particular, they have started work to create a more advanced in-situ brain cryopreservation perfusion room that allows for automated perfusion and data collection in a temperature-controlled enclosure.
Former Ellison Scholar James Shorter, Ph.D., (University of Pennsylvania Medical School) continues to develop heat-shock proteins that
antagonize the misfolding of the amyloid-beta protein linked to Alzheimer's disease with funding from Life Extension. Dr. Shorter has been identifying the
most effective of these heat shock proteins, and has found that many of them are also effective against the misfolding of the tau protein that causes
Alzheimer's disease. He is now doing his testing in human neuroblastoma cells rather than yeast. He is also trying to convert misfolded amyloid-beta and
tau protein into non-toxic species. If this research is successful, it could lead to the first real treatment for Alzheimer's disease, a condition that is
currently irreversible, always leading to increasing dementia and ultimate death. Dr. Shorter has also been working with researchers in Switzerland in
using his heat-shock proteins to reverse the protein aggregation that causes Parkinson's disease.
For many years Life Extension has been funding cryobiological research that would allow for increasingly long-term, low-temperature maintenance or storage
of transplantable organs. Too often vitally-needed transplantable organs from accident victims do not reach needy patients soon enough because the organs
deteriorate so rapidly. The demand for transplantable organs greatly exceeds the supply. Just as refrigerators and freezers preserve food, low-temperatures
could preserve transplantable organs. The lower the temperature, the longer the organs could be preserved. But because freezing damages all biological
tissues, cryoprotectants (anti-freeze solutions) must be developed to prevent ice formation. 21st Century Medicine (21CM)
is the major cryobiological research company that Life Extension has been funding. 21CM has developed a relatively non-toxic cryoprotectant solution. The
word "relatively" must be emphasized, because all cryoprotectant solutions have some toxicity. For that reason, cryobiologists try to use just enough
cryoprotectant to prevent ice formation, but not enough to damage tissues as a result of toxicity. Unfortunately, the organ that is in greatest demand for
transplant, the kidney, has posed serious problems for cryobiologists. The outer layers of the kidney receive high blood flow, whereas the inner layers
receive low blood flow. So the challenge has been to get enough cryoprotectant into the kidney from the bloodstream to prevent ice formation in the inner
layer without causing toxic damage to the outer layer of the kidney. The year 2016 has seen major technical breakthroughs by 21CM on this problem. 21CM can
now substantially reduce or eliminate ice formation in the inner layers of the kidney without toxic damage to the outer layers of the kidney.
Up to 900,000 organ transplants are needed each year in the United States alone, compared to about 30,000 transplants actually carried out each year. Many exciting advances are leading to ways to eliminate the organ shortage, but an avalanche of new organs will create a new problem – how to manage all of the resulting transplants. Even without the added stress of a 30-fold increase in the number of transplants, transplantation today is a frenetic endeavor, with Lear jets rushing human hearts to their recipients before their short survival times outside the body expire, surgeons performing transplants in the middle of the night, families constantly on standby, waiting to go to the hospital at a moment’s notice to receive a life-saving organ, and with kidneys and other organs being transplanted with considerable storage damage and with less than perfect matches because the alternative is to discard the poorly matched organs as their viable storage times expire.
To learn more information about 21CM and cryopreservation, please keep reading below under “Cryopreservation Projects.”
Every day in 2013, 1,600 Americans died of cancer,17 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 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 Life Extension’s various cancer research initiatives over the past year.
Life Extension is funding a pancreatic cancer trial at City of Hope Hospital in Los Angeles, California with a 21-person target enrollment. The clinical trial includes a supplementation package to be used with standard pancreatic cancer drugs. The clinical trial continues to accrue patients with a targeted completion date set for 2018.
Study title: A Pilot Study of Gemcitabine, Abraxane, Metformin and a Standardized Dietary Supplement (DS) in Patients With Unresectable Pancreatic Cancer
- To assess the compliance, toxicity and feasibility of administering gemcitabine (gemcitabine hydrochloride), Abraxane (paclitaxel albumin-stabilized nanoparticle formulation), metformin (metformin hydrochloride), and the dietary supplement (DS).
- To assess the response rate associated with this combination therapy in pancreatic cancer patients.
- To assess the progression-free survival and overall survival of all patients who start protocol therapy, and describe the outcomes based on measures of compliance during the lead-in week, and compliance with supplement during chemotherapy.
- To collect and analyze peripheral blood and pre-treatment biopsy samples for an exploratory analysis of biological correlatives.
- To assess quality of life utilizing the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire.
Patients receive gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) on days 1, 8, and 15. Patients also receive metformin hydrochloride orally (PO) twice daily (BID) starting day -6 and dietary supplement PO BID starting day -3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months.
This pilot phase I trial studies the side effects of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, metformin hydrochloride, and a standardized dietary supplement in treating patients with pancreatic cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Metformin hydrochloride, used for diabetes, may also help kill cancer cells. Dietary supplements (curcumin, vitamin D, vitamin K2, vitamin K1, B-6, high selenium broccoli sprouts, epigallocatechin gallate, L-carnitine, garlic extract, genistein, zinc amino chelate, mixed toxopherols, ascorbic acid, D-limonene) can block different targets in the cancer cell simultaneously and may slow down cancer growth. Giving gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, and metformin hydrochloride with a dietary supplement may work better in treating patients with pancreatic cancer that cannot be removed by surgery.
Pancreatic Adenocarcinoma Unresectable Pancreatic Carcinoma
Drug: Gemcitabine Hydrochloride Drug: Paclitaxel Albumin-Stabilized Nanoparticle Formulation Drug: Metformin Hydrochloride Dietary Supplement: Therapeutic Dietary Intervention Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment Masking: None (Open Label)
Primary Purpose: Treatment
Primary Outcome Measures:
- Feasibility of the combination of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, metformin hydrochloride, and a dietary supplement [Time Frame: Up to 24 months]
Feasibility is defined at 1 or fewer patients experiencing a dose limiting toxicity within the first 6 patients.
- Compliance of the combination of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, metformin hydrochloride, and a dietary supplement (percent of patients who are fully compliant) [Time Frame: Up to 24 months]
The percent of patients who are fully compliant in the first week will be estimated with a 95% confidence interval. The compliance will be measured similarly for each course prior to study treatment discontinuation. The impact of less than full compliance (both during the lead-in period and during chemotherapy) on the biomarkers and outcome, and qualitatively study patient reasons and specific supplement patterns related to non-compliance will be explored.
- Toxicity of the combination of gemcitabine hydrochloride, paclitaxel albumin-stabilized nanoparticle formulation, metformin hydrochloride, and a dietary supplement (National Cancer Institute Common Terminology for Adverse Events criteria version 4) [Time Frame: Up to 24 months]
Summarized using the National Cancer Institute Common Terminology for Adverse Events criteria version 4. Tables will summarize the highest grade per patient that is possibly related to treatment, and the number of patients requiring dose modifications will also be presented.
Secondary Outcome Measures:
- Progression-free survival [Time Frame: Up to 24 months]
Evaluated using the Kaplan-Meier methods.
- Overall survival [ Time Frame: Up to 24 months ]
Evaluated using the Kaplan-Meier methods.
- Time to treatment failure [Time Frame: Up to 24 months]
Evaluated using the Kaplan-Meier methods.
Other Outcome Measures:
- Analysis of biological correlates (Peripheral blood will be evaluated) [Time Frame: Up to 24 months]
Peripheral blood will be evaluated. Standard descriptive methods will be used to summarize the baseline levels and the changes from baseline (i.e., after treatment) in order to examine whether observed patterns are consistent with hypothesized patterns.
- Quality of life, assessed using the FACT-G questionnaire [Time Frame: Up to 24 months]
Standard descriptive methods will be used to summarize the baseline levels and the changes from baseline (i.e., after treatment) in order to examine whether observed patterns are consistent with hypothesized patterns.
Study Start Date:
Estimated Study Completion Date:
Estimated Primary Completion Date:
January 2018 (Final data collection date for primary outcome measure)