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BioTime Demonstrates Successful Age Reversal

March 16, 2010

BioTime, Inc. a biotechnology company that develops and markets products in the field of stem cells and regenerative medicine, today announced the publication of a scientific paper titled "Spontaneous Reversal of Developmental Aging in Normal Human Cells Following Transcriptional Reprogramming." The article was released online in the peer-reviewed journal Regenerative Medicine in advance of the print publication. The demonstration that the aging of human cells can be reversed may have significant implications for the development of new classes of cell-based therapies targeting age-related degenerative disease.

In the article, BioTime and its collaborators demonstrate the successful reversal of the developmental aging of normal human cells. Using precise genetic modifications, normal human cells were induced to reverse both the "clock" of differentiation (the process by which an embryonic stem cell becomes the many specialized differentiated cell types of the body), and the "clock" of cellular aging (telomere length). As a result, aged differentiated cells became young stem cells capable of regeneration.

The paper sheds light on the recent controversy over the aged status of induced pluripotent stem (iPS) cells. iPS cell technology has excited the scientific community because it has been demonstrated to be a method of transforming adult human cells back to a state very similar to embryonic stem cells (reversing the process of development) without the use of human embryos. However, recent reports have 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 (that is, the iPS cells may be prematurely old). This problem has been called "the Achilles heel of iPS cell technology." BioTime scientists and their collaborators show in this paper 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 reported in this paper is part of BioTime's broader research strategy to advance the capabilities of the company's proprietary ReCyte technology. ReCyte is being developed as a means of implementing iPS technology on an industrial scale. The study published today intentionally used older viral-based means of introducing genes. Therefore, BioTime plans further studies of cellular aging reversal using its proprietary ReCyte technology. BioTime has filed new patent applications on methods used in the paper to reverse the developmental aging of cells and the use of transcriptional reprogramming to produce young cells of many types for use in regenerating tissues affected by aging.

"This is just the beginning of some really fascinating new possibilities for intervening in age-related disease," said Michael West, President and Chief Executive Officer of BioTime, Inc. "We believe that these technologies will have a significant impact on the future of medicine. However, it is important to underscore that much work needs to be done to translate these findings into safe and efficacious therapies."

"At the National Institute on Aging, we reviewed many proposals from leading gerontologists seeking means to understand and intervene in the biology of aging," said Robert Butler, Founding Director of the National Institute on Aging, now President of the International Longevity Center, and Board member of BioTime. "These are just the type of basic discoveries that if funded on a larger scale, could help us ward off the enormous wave of health care expenditures coming our way as a result of the aging baby boom population.

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 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.

Since human embryonic stem cells are derived from discarded human embryos created in the process of in vitro fertilization (IVF), their use in research has been controversial. However, induced pluripotent (iPS) stem cells can be created using noncontroversial adult cells, such as skin cells, rather than embryonic cells. The alteration of specific genes in adult cells allows them to be transformed into iPS cells that are very similar to hES cells.

BioTime plans to eventually utilize these technologies for human therapeutic applications. However, the technologies reported in BioTime's scientific article are early stage research findings. Cell-based therapeutics require years of extensive preclinical testing and development prior to being used in an effort to treat humans.

The authors of the article include: Dr. Homayoun Vaziri, Andriana Guigova, and Jonathan Teichroeb of the Ontario Cancer Institute; Ilyas Singec and Evan Snyder of the Burnham Institute for Medical Research; David Larocca of Mandala Biosciences, LLC; Laura Briggs, Jessica Wheeler, and William H. Andrews of Sierra Biosciences; Rodolfo Gonzales of the Scripps Research Institute; and Karen B. Chapman, Markus D. Lacher, Hal Sternberg, Walter D. Funk, and Michael D. West from BioTime, Inc.

Additional information about the use of BioTime's stem cell technology is available at www.biotimeinc.com.

Source: BioTime, Inc.

March 16, 2010.
(doi:10.2217/rme.10.21)

Here is the Research Article:
Spontaneous reversal of the developmental aging of normal human cells following transcriptional reprogramming
H Vaziri*, KB Chapman*, A Guigova*, J Teichroeb*, MD Lacher*, H Sternberg*, I Singec*, L Briggs*, J Wheeler*, J Sampathkumar*, R Gonzalez*, D Larocca*, J Murai*, E Snyder*, WH Andrews*, WD Funk* & MD West*?
?Author for correspondence


Aim: To determine whether transcriptional reprogramming is capable of reversing the developmental aging of normal human somatic cells to an embryonic state. Materials & methods: An isogenic system was utilized to facilitate an accurate assessment of the reprogramming of telomere restriction fragment (TRF) length of aged differentiated cells to that of the human embryonic stem (hES) cell line from which they were originally derived. An hES-derived mortal clonal cell strain EN13 was reprogrammed by SOX2, OCT4 and KLF4. The six resulting induced pluripotent stem (iPS) cell lines were surveyed for telomere length, telomerase activity and telomere-related gene expression. In addition, we measured all these parameters in widely-used hES and iPS cell lines and compared the results to those obtained in the six new isogenic iPS cell lines. Results: We observed variable but relatively long TRF lengths in three widely studied hES cell lines (16.09?21.1 kb) but markedly shorter TRF lengths (6.4?12.6 kb) in five similarly widely studied iPS cell lines. Transcriptome analysis comparing these hES and iPS cell lines showed modest variation in a small subset of genes implicated in telomere length regulation. However, iPS cell lines consistently showed reduced levels of telomerase activity compared with hES cell lines. In order to verify these results in an isogenic background, we generated six iPS cell clones from the hES-derived cell line EN13. These iPS cell clones showed initial telomere lengths comparable to the parental EN13 cells, had telomerase activity, expressed embryonic stem cell markers and had a telomere-related transcriptome similar to hES cells. Subsequent culture of five out of six lines generally showed telomere shortening to lengths similar to that observed in the widely distributed iPS lines. However, the clone EH3, with relatively high levels of telomerase activity, progressively increased TRF length over 60 days of serial culture back to that of the parental hES cell line. Conclusion: Prematurely aged (shortened) telomeres appears to be a common feature of iPS cells created by current pluripotency protocols. However, the spontaneous appearance of lines that express sufficient telomerase activity to extend telomere length may allow the reversal of developmental aging in human cells for use in regenerative medicine.

[Narcodran]

Barbara:

Thanks you so much for posting this; BioTime is headed up by a group of first class geniuses who are hugely serious about what they are trying to accomplish...literally reversal of the aging/senescence process.

I personally do not believe that attitudes leading to the statement
"Cell-based therapeutics require years of extensive preclinical testing and development prior to being used in an effort to treat humans." will be allowed to impede direct clinical application once age-reversal applications begin to show their power...

Robert

[reiruviartugs]

I agree with you Yorkere 100%.