I established some months back that a reinterpretation of the Noah story in concert with other conforming conjectures told a story of the establishment of human colonies on the post Pleistocene Nonconformity Earth. The text itself retains survivals that supported both the story and the likelihood this text was a translation of an original report in an original language.
It follows that the initial leaders of the colony retained their original life spans during the millennial build out of the colony. We have the lifespan of Methuselah in particular.
Science is now clearly unraveling the necessary protocols to extend human life spans and this report by this company in the midst of the necessary research endeaver pretty clearly spells out were we are at. There is obviously rising optimism and the suggestion that this generation may well gain some of the benefits.
If we accept the Methuselah story as just given and I suggest that my reinterpretation gives us a consistent data base and little choice, then this work is about restoring that level of human longevity. It is not about immortality but about been able to spend a great number of years in the fullness of health on earth.
That is well worth supporting.
Overview of BioTime’s Reversal of the Aging of Human Cells
An Overview with Questions & Answers
Summary:
- BioTime and its collaborators reported on March 16, 2010 in a scientific paper titled “Spontaneous Reversal of the Developmental Aging of Normal Human Cells Following Transcriptional Reprogramming” the reversal of human cellular aging. The paper is online at
- The Company reported that by selecting for cells with sufficient levels of the immortalizing protein telomerase, they were able to reset the clock of aging back to the embryonic state.
- Using the new technologies of reprogramming, BioTime scientists showed that time’s arrow of development, as well as aging, could be reversed.
- BioTime revealed why existing Induced Pluripotent Stem (iPS) cell lines being studied showed signs of premature aging, and a means to overcome that roadblock.
- This new capability does not require the use of human embryos or egg cells.
- BioTime’s reversal of developmental aging may be the seed for future technologies that will one day allow young cells of any kind to be produced that might be useful for aging patients in repairing the heart, the blood system, the brain, and the retina, as well as many others applications. In this way, we might increase the “healthspan,” that is, the years free from expensive and debilitating disease.
The Role of Gerontological Research in Society Today
The science of the biology of aging (gerontology) is increasingly a strategic focus for the medical community, the pharmaceutical industry, and government. The United States, China, and many other developing countries are about to experience an unprecedented tsunami of aging people with an unprecedented demand for medical care associated with the chronic debilities of aging. Data on this demographic trend published by the Bureau of the Census is available online on this site or from the US Census Bureau at http://www.census.gov/prod/2006pubs/p23-209.pdf.
A Brief Summary of BioTime’s Technology
The approach BioTime scientists have taken to devise new strategies for the treatment of age-related disease begins with the recognition that the human life cycle uses both “mortal” and “immortal” cells. One of the remarkable things about life is that it continues generation after generation through our children, while the individual human being inevitably ages and dies. Curious about how some cells (those in the reproductive lineage also known as the germ-line) accomplish this unending task, gerontologists began to investigate the internal molecular machinery of life, looking for the differences in mortal and immortal cells. “Immortal” cells are those of the reproductive lineage that have the potential to continually make babies generation after generation, forever. In contrast, the cells of the human body such as blood, brain, and muscle cells (somatic cells) have an irrevocably finite lifespan and are therefore called “mortal.” An amazing fact about life is that our bodies are the offshoots of lines of these immortal cells that have been proliferating since the dawn of life on earth. They, unlike the individual human being, have no dead ancestors. So, the question is, “Why?”
Figure 1. The dichotomy of germ-line and somatic cells. Germ-line cells continue in an unlimited immortal proliferation of mitosis and meiosis (the latter not shown) while somatic cells are destined to die with the individual.
The “Clock” of Cellular Aging
In the 1960s, Leonard Hayflick demonstrated that cells from the human body have a finite capacity to divide. That is, when grown in the laboratory, they divide perhaps 70 times and then age and stop. In the years that followed, gerontologists began to study this aging of cells in the lab dish in an effort to solve the riddle of human aging. Finally, in the late 1990s, the use of Dr. Hayflick’s cellular aging model led to the identification of the central clocking mechanism. The “clock” of cellular aging was shown to be in the DNA of every cell, in a region called the “telomere” or “end part” of the chromosomes. Telomeres have often been compared to the protective plastic ends on our shoelaces (see Fig. 2 below). In 1998 it was demonstrated that a gene expressed in the germ-line cells called telomerase continually rewinds this clock of aging, keeping it at the appropriate embryonic setting, allowing the reproductive cells to proliferate without limit and making babies born young. However, when cells begin to branch out to make the human body, the immortalizing enzyme is turned off and as a result, telomeres shorten every time cells divide (hence their mortality). Telomeres are long enough at the beginning of life to allow all the cell doublings necessary to make a baby, to allow the person to grow to adulthood, and to allow cell division in the adult for up to approximately a century. However, progressively over time, telomeres shorten; aged (senescent) cells accumulate in tissues throughout the body and are thought to lead to age-related changes in the body.
Figure 2. Human chromosomes are shown in blue. Telomeres are illuminated in green at the chromosome ends.
It was appreciated very early on that cancer cells have abnormally reactivated the immortalizing enzyme, telomerase, giving the rapidly proliferating tumor cells the ability replicate out of control forever. So, to intervene in aging without causing an undue risk of cancer, scientists sought a way to carefully turn telomerase on when needed and then to turn it off again to make young (but not immortal) cells to repair the tissues worn out with age in the human body.
The approach settled on was to attempt to isolate cells from the immortal human germ-line that naturally maintain long and youthful telomeres when they are in the germ-line state and that turn off telomerase when the cells of the human body begin to form as they do naturally in each human generation. In 1998 the first such naturally immortal cells were cultured from the human germ-line and they were called “human embryonic stem cells.”
There was a great deal of excitement in the scientific community relating to these cells because for the first time it was possible to devise technologies that would allow the manufacture of all the cells of the human body on a very large scale. This, in principle, could lead to a wide array of products useful in repairing tissues like the heart, brain, bones, eyes, and many other tissues that have never been possible to repair before. As a result, this new field came to be called “regenerative medicine.”
However, the fact that these cells came from the earliest stages of human life, shortly after the egg cell is fertilized by sperm, has caused the use of human embryonic stem cells to be controversial for some people. In 2001, President Bush allowed federal funding to be used on embryonic stem cell lines created before 2001, but not those made thereafter. This despite the fact that the embryos had not yet begun to develop (i.e., were not yet a pregnancy), and were destined to be discarded in the process of in vitro fertilization (IVF).
A Cellular Time Machine
In 1997 when Dolly the sheep was cloned, it occurred to some scientists that the transfer of DNA from the aged cells of the body into an egg cell was capable of changing the state of the cell in what could be compared to a cellular time machine. Despite the rumors that Dolly the sheep was born old because she came from an aged breast cell (hence her being named after Dolly Parton), scientists soon demonstrated that the cloning process really could reverse both the process of specialization of the body cell to make embryonic cells again, and surprisingly, cloning could also reset the clock of aging in cells. So, just like the immortal perpetuation of the species, cloning would allow a baby animal cloned from an aged body cell to be born young, and theoretically, the process could be repeated forever. If this could be tapped in the cause of medicine, it might be possible, similarly, to make unlimited young replacement body cell types forever to repair cells and tissues worn out with age. Early efforts to clone human embryonic stem cells, a process called therapeutic cloning to distinguish it from human reproductive cloning (the cloning of a human being), led to cloned embryos that would only grow to a small number of cells. In addition to the difficulties in making human therapeutic cloning efficient, the difficulty of sourcing human egg cells and the intense ethical controversy over the use of cloning in medicine made progress in the field relatively difficult. The good news is that in the years that followed, scientists identified some of the molecules within the egg cell that accomplish the work of cloning. These discoveries allowed these molecules to be used in such a way that egg cells were not required and no embryos were cloned. In other words, a cell type, such as a skin cell, could be coaxed back to an embryonic state in an ethically noncontroversial manner. Because these cells do not come from an embryo, they are called “induced pluripotent stem (iPS) cells” instead of embryonic stem cells. This transformation of a body cell back to an embryonic state uses proteins that are master regulators of other genes called “transcription factors.” Therefore this process is called “transcriptional reprogramming” or “iPS” technology. These cells exhibit pluripotent capabilities, meaning they have the potential to mature into all of the cell types or tissues types — skin, blood, bone or retinal cells, for example.
Figure 3. By understanding the molecules called “transcription factors” within the egg cell that is capable of returning cells in the body back to an embryonic state, they were able to turn back the clock of biology, a process called “reprogramming.”
However, recently, scientists reported that iPS cells show evidence of premature aging when induced to become cells of the body such as blood-forming cells (Feng et al, 2010). In some cells that have abnormal regulation of telomerase — an enzyme that maintains telomere length, there was evidence that iPS could at least partially rewind the clock of aging (Agarwal; et al, 2010); however, suggestions that iPS cells might generally be prematurely old caused concern over the new technology.
Reversal of Developmental Aging
In BioTime’s report, we show that the premature aging observed in the existing iPS cell lines studied was due to the fact that the telomere clock of cellular aging in at least many of the lines being used in the scientific community is set at a relatively old (short) level. However, using a system where cells with the same DNA type at young embryonic states, as well as aged states were used, BioTime scientists reported that by looking for cells with sufficient levels of the immortalizing protein telomerase, they were able to reset the clock of aging back to the embryonic state. So, both the process of development wherein the germ-line cells specialize into the cells of the body, and also the telomere clock of aging was reported in the study. This reversal of developmental aging may be the seed for future technologies that will one day allow young cells of any kind to be produced for aging patients for use in repairing the heart, the blood system, the brain, and the retina, as well as many others applications.
Figure 4. In BioTime’s publication, the clock of cellular aging (telomere length) was measured in cells at the very beginning of life (embryonic stem cells). Then body cell types were made from those cells and they were observed to become mortal and to age from telomere shortening. Then, using these cells with the same DNA type, the application of iPS cell technology with careful studies of the levels of the immortalizing gene telomerase, allowed the complete reversal of developmental aging.
A presentation Dr. Michael West, CEO of BioTime Inc., recently gave on this technology is available online at
Shaping a U.S. Policy on Interventional Gerontology
We are at a critical nexus in our history. The aging of our population is occurring at an unprecedented rate due to the aging of the baby boom population. The cost of this age wave will cause economic, as well as personal human suffering. The United States has historically approached serious challenges in the past with courage and creativity, with an eye on the compassionate application of science. There is just enough time to begin to apply the new advances in regenerative medicine if we begin today.
Figure 5. Summary of the reversal of developmental aging. In normal development and aging, the immortal cells from the reproductive lineage of cells make all of the cells of the human body that will age and die with the individual. Using the new technologies of reprogramming, BioTime scientists showed that time’s arrow of development as well as aging could be reversed, potentially one day leading to the ability to make any young cell type useful in repairing those worn out with age.
Dr. Michael D. West is the Chief Executive Officer of BioTime, Inc. (NYSE-Amex: BTIM) and OncoCyte Corporation of Alameda, California. The Companies are focused on developing an array of research and therapeutic products using human embryonic stem cell technology. He received his Ph.D. from Baylor College of Medicine in 1989 concentrating on the biology of cellular aging. He has focused his academic and business career on the application of developmental biology to the age-related degenerative disease. He was the Founder of Geron Corporation of Menlo Park, California (Nasdaq: GERN) and from 1990 to 1998 he was a Director, and Vice President, where he initiated and managed programs in telomerase diagnostics, oligonucleotide-based telomerase inhibition as anti-tumor therapy, and the cloning and use of telomerase in telomerase-mediated therapy wherein telomerase is utilized to immortalize human cells. From 1995 to 1998 he organized and managed the research collaboration between Geron and its academic collaborators James Thomson and John Gearhart that led to the first isolation of human embryonic stem and human embryonic germ cells. From 1998 to 2007 he was President and Chief Scientific Officer at Advanced Cell Technology, Inc. (OTCBB: ACTC) where he managed programs in animal cloning, human somatic cell nuclear transfer, retinal differentiation, and ACTCellerate, a technology for the multiplex derivation and characterization of clonal human embryonic progenitor cell lines.
About BioTime, Inc.
BioTime, headquartered in Alameda, California, is a biotechnology company focused on regenerative medicine, blood plasma volume expanders, and low temperature medicine. BioTime develops and markets research products in the field of stem cells and regenerative medicine through its wholly owned subsidiary Embryome Sciences, Inc. BioTime’s subsidiary OncoCyte Corporation focuses on the therapeutic applications of stem cell technology in cancer. BioTime also plans to develop therapeutic products in China for the treatment of ophthalmologic, skin, musculo-skeletal system and hematologic diseases, including the targeting of genetically modified stem cells to tumors as a novel means of treating currently incurable forms of cancer through its subsidiary BioTime Asia. In addition to its stem cell products, BioTime markets blood plasma volume expanders and related 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 U.S. by Hospira, Inc. and in South Korea by CJ CheilJedang Corp. under exclusive licensing agreements. Additional information about BioTime can be found on the web at www.biotimeinc.com.
Forward-Looking Statements
Statements pertaining to future financial and/or operating results, future growth in research, technology, clinical development and potential opportunities for the company and its subsidiary, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as “will,” “believes,” “plans,” “anticipates,” “expects,” “estimates,”) should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company’s business, particularly those mentioned in the cautionary statements found in the company’s Securities and Exchange Commission filings. The company disclaims any intent or obligation to update these forward-looking statements.
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