Life Extension Magazine September 2011
Research Funded by Life Extension® Could Lead to Therapies That Reverse Human Aging
The purpose of the Life Extension Foundation® is to fund the development of therapies to provide mankind with an indefinitely extended healthy life span. In order to reach this goal, we fund pioneering scientific research to learn how to reverse human aging.
Every year, Life Extension funds millions of dollars of research aimed at the development of path-breaking therapies to cure the diseases of aging and reverse aging itself. Our objective is to help you live longer now and extend your life span to 100 and beyond in the future.
This article describes research that Life Extension funded to transform aging cells into young stem cells capable of being developed into new therapies to cure age-related diseases and reverse aging. This study has advanced to a phase where scientists are attempting to rejuvenate the vascular and immune systems of old mice with induced pluripotent stem cells (iPS). If this animal phase is successful, an attempt will be made to adapt the same approach for use in humans.
BioTime Rejuvenates Aging Cells With iPS Technology
Just as human embryos develop into adult humans with a wide variety of specialized cells, human embryonic stem cells (hES) can potentially be developed into any type of young healthy tissue, which could, eventually, be transplanted into people suffering from the diseases of aging and aging itself.
However, the practice of deriving hES cells from human embryos is controversial because of opposition to using human embryos for research purposes. A few years ago, it was discovered that aging human cells can be reprogrammed back to their embryonic state. These cells are called induced pluripotent stem cells (iPS). This technology holds the promise of using an aging person’s own cells to develop young regenerative tissues that could be used to treat and, possibly, cure age-related diseases such as heart disease, stroke, and cancer.
Some studies with iPS cells have shown that they don’t work as well as hES cells in stimulating the production of telomerase, the enzyme that maintains healthy cells by keeping the length of their telomeres intact. Telomeres are found at the ends of chromosomes in dividing cells. Every time the cell divides, it loses some of the units that make up its telomeres. As the telomeres become shorter, their ability to protect the integrity of the chromosomes degrades until the chromosomes malfunction and the cells die.
This process can be compared to the role that the plastic tips at the ends of shoelaces play in keeping the shoelaces from unraveling and becoming useless.
In 2009, the Life Extension Foundation® (LEF) funded $250,000 to BioTime for a study that showed that, under special conditions, some iPS cells can work as well as hES cells.
In 2010, LEF contributed $2 million to BioTime’s subsidiary ReCyte Therapeutics to help develop novel, innovative, regenerative therapies to treat the diseases of aging and, perhaps, aging itself.
Restoration of Replicative Life Span in Five Human Cell Types Validates Previous Published Report of Reversal of Developmental Aging by Transcriptional Reprogramming
Dr. Michael West, CEO of BioTime, Inc., and its subsidiary ReCyte Therapeutics, Inc., recently made a presentation at the French-American Biotech Symposium (FABS 2011) on “New Therapeutic Approaches of Aging” showing data for the first time on the restoration of cell life span using transcriptional reprogramming technology.
On March 16, 2010, BioTime announced the publication of a peer-reviewed scientific paper reporting that iPS cell reprogramming technologies could, under certain conditions, reverse the developmental aging of human cells. In other words, through genetic modification, cells from the human body can be reverted back to an embryonic state similar to that of embryonic stem cells, which are capable of developing into all other cell and tissue types. In the same publication, BioTime reported that these reprogramming technologies could reset the telomere clock of cellular aging. At the symposium, Dr. West presented new data validating this technology as it relates to actual cell life span.
In particular, new evidence was presented that the technique is capable not only of resetting telomere length, but also of restoring the proliferative life span of aged human cells back to that seen in cells obtained from young tissues. Specifically, BioTime scientists measured the replicative life span of five human cell types derived from aged human cells that had been returned to the embryonic state using transcriptional reprogramming. These life spans, which greatly exceeded the normal life expectancy of the original aged cells, provide the first definitive evidence that such technologies provide a means of manufacturing young cells genetically identical to the cells of an aged patient.
“Ever since Dr. Leonard Hayflick’s original observations that human body cells have a finite capacity for cell division, researchers around the world have sought to discover a means to reset that clock for diverse clinical applications,” said West. The rising worldwide demand for novel therapeutics targeting the chronic degenerative diseases of aging makes these new technologies timely, and strategic for the biotechnology industry. We plan to aggressively pursue the commercialization of therapeutic products from this platform, beginning with the vascular products of our ReCyte Therapeutics subsidiary.”
This was the fourth French-American Biotech Symposium co-organized by The Office for Science and Technology of the French Embassy in Washington, DC, and Eurobiomed, a French biotech cluster dedicated to health sciences, in partnership with the Gladstone Institute for Virology and Immunology.
Regenerative medicine refers to the development and use of therapies based on human embryonic stem (hES) cell or induced pluripotent stem (iPS) cell technology. These therapies will be designed to regenerate healthy tissues to replace tissues afflicted by degenerative diseases. The great scientific and public interest in regenerative medicine lies in the potential of hES and iPS cells to become all of the cell types of the human body. Many scientists therefore believe that hES and iPS cells have considerable potential as sources of new therapies for a host of currently incurable diseases such as diabetes, Parkinson’s disease, heart failure, arthritis, muscular dystrophy, spinal cord injury, macular degeneration, hearing loss, liver failure, and many other disorders where cells and tissues become dysfunctional and need to be replaced.
In 2010, BioTime announced the publication of a peer-reviewed scientific paper titled “Spontaneous Reversal of the Developmental Aging in Normal Human Cells Following Transcriptional Reprogramming” in the journal Regenerative Medicine. The discovery that the aging of human cells can be reversed may have significant implications for targeting age-related degenerative disease through the development of new classes of cell-based therapies. The article is available online at www.futuremedicine.com/doi/abs/10.2217/rme.10.21.
BioTime and its collaborators in the article demonstrated the successful reversal of the developmental aging of normal human cells. Normal human cells were induced to reverse the “clock” of differentiation (the process by which an embryonic stem cell becomes the many specialized differentiated cell types of the body), as well as the “clock” of cellular aging (telomere length), using precise genetic modifications. Aged differentiated cells became young stem cells capable of regeneration as a result.
The paper threw some light on the controversy over the aged status of induced pluripotent stem (iPS) cells. The scientific community has been excited over iPS technology as it has been demonstrated to be a means of transforming adult human cells back to a state very similar to that of embryonic stem cells (reversing the process of development) without the use of human embryos. However, there were reports that suggested that iPS cells, though very similar to embryonic stem cells in many respects, may not have the normal replicative potential of embryonic stem cells (i.e., the iPS cells may be prematurely old). This problem has been called “the Achilles heel of iPS cell technology.” In this paper, BioTime scientists and their collaborators showed that many iPS cell lines currently being circulated in the scientific community have short telomeres, meaning that their clock of cellular aging is still set at the age of relatively old cells. However, among these prematurely old cells, other cells can be found with sufficient levels of telomerase (a protein that keeps reproductive cells young) that allow these cells to reverse cellular aging all the way back to the very beginning of the human life cycle.
The research presented in this paper is part of BioTime’s broader research strategy to advance the capabilities of the company’s proprietary ReCyte™ technology, which is being developed as a means of implementing iPS technology on an industrial scale. Whereas the study published in 2010 intentionally used older, viral-based means of introducing genes, BioTime now plans further studies of cellular aging reversal using its proprietary ReCyte™ technology specifically designed to rapidly reprogram cells in a manner expected to prevent the telomeric and other genetic abnormalities afflicting previous iPS cell approaches.
About BioTime, Inc.
BioTime, headquartered in Alameda, California, is a biotechnology company focused on regenerative medicine and blood plasma volume expanders. Its broad platform of stem cell technologies is developed through subsidiaries focused on specific fields of applications. BioTime develops and markets research products in the field of stem cells and regenerative medicine, including a wide array of proprietary ACTCellerate™ cell lines, culture media, and differentiation kits. BioTime’s wholly owned subsidiary ES Cell International Pte Ltd (ESI) has produced clinical-grade human embryonic stem cell lines that were derived following principles of Good Manufacturing Practice and currently offers them for use in research. BioTime’s therapeutic product development strategy is pursued through subsidiaries that focus on specific organ systems and related diseases for which there is a high unmet medical need. BioTime’s majority owned subsidiary Cell Cure Neurosciences, Ltd., is developing therapeutic products derived from stem cells for the treatment of retinal and neural degenerative diseases. Cell Cure Neuroscience’s minority shareholder Teva Pharmaceutical Industries has an option to clinically develop and commercialize Cell Cure’s OpRegen™ retinal cell product for use in the treatment of age-related macular degeneration.
BioTime’s subsidiary OrthoCyte Corporation is developing therapeutic applications of stem cells to treat orthopedic diseases and injuries. Another subsidiary, OncoCyte Corporation, focuses on the therapeutic applications of stem cell technology in cancer. ReCyte Therapeutics, Inc., is developing applications of BioTime’s proprietary iPS cell technology to reverse the developmental aging of human cells to treat cardiovascular and blood cell diseases. BioTime’s newest subsidiary, LifeMap Sciences, Inc., is developing an online database of the complex cell lineages arising from hES and iPS cells to guide basic research and to market BioTime’s research products. In addition to its stem cell products, BioTime develops blood plasma volume expanders, blood replacement solutions for hypothermic (low temperature) surgery, and technology for use in surgery, emergency trauma treatment and other applications. BioTime’s lead product, Hextend®, is a blood plasma volume expander manufactured and distributed in the US by Hospira, Inc. and in South Korea by CJ CheilJedang Corp. under exclusive licensing agreements. Additional information about BioTime, ReCyte Therapeutics, Cell Cure, OrthoCyte, OncoCyte, BioTime Asia, and ESI can be found on the web at www.biotimeinc.com.