Dr.

Satya Ambrose Telomere Extension, Astragalus, & the Immune System Intro to Chinese Medicine Honors Project

Rodney Billington June 17, 2012

In 2010, I had attended a presentation on bioengineering that was given by Sierra Sciences at the University of Nevada, Reno, where they addressed telomerase-induced telomere extension, specifically using Astragalus Membranaceus, which was shown in 2006 to generate telomerase activity at very low levels. Telomere extension research has heavy implications on the immune system, which will be covered in the latter part of this paper. Research from the last 30 years has shown that telomeres are able to be lengthened using telomerase. In 2009, Elizabeth Blackburn, Jack Szostak, and Carol Greider were awarded the Nobel Prize for their work in discovering the structure and mechanisms of telomeres and telomerase from their prior 25 years of research and clinical trials in microorganisms. However, the data was not able to be proved in humans until the telomerase enzyme was successfully cloned in human cells, which wasn’t achieved until 1997. Subsequently, in 1998, Geron Corporation added the gene for telomerase to normal human cells, creating a line of telomerase-positive cells. They found that cells from this line were able to divide indefinitely, without entering replicative senescence, as an unmodified cell culture would. This, in short, states that human cell lines could be made immortal. In 1999, an experiment at the National Center of Biotechnology deleted the telomerase gene in mice and bred them for six to seven generations, whereby the mice showed many signs akin to human aging: graying hair, frailness, spontaneous malignancies, and reduced capacity for wound healing. The results of this experiment hint that the immune system of the mice may have also been hindered by the deletion of telomerase. In 2000, Geron Corporation then reversed the experiment by adding telomerase to old human skin cells that were grown on the backs of immunodeficient mice and replicated these cells for 25 generations (past the theoretical limit of unaltered cells). A DNA array analysis of the artificially “telomerized” skin, young and old control skins revealed that the telomerized skin was identical in both appearance and genetic expression. Retrogenetically (I made this term up) repairing the skin allowed for a greater immune response to foreign pathogens. This has great implications for the immune response in the elderly population who suffer from a hindered immune system. A study of 143 people at the University of Utah in 2003 found that mortality rates of those with shorter telomeres were nearly twice as high as those with longer telomeres. Mortality as a result of heart disease was nearly three times higher in those with shorter telomeres. This provides a possible link between telomere length and age-related diseases. In 2006, Geron Corporation discovered a nutraceutical derived from Astragalus membranaceus that generated telomerase activity at very low levels, which was then on the market by 2007, going by the name TA-65. A year later, Sierra Sciences (the company of which I attended their presentation) discovered a synthetic drug-like molecule that induced cells to produce telomerase at significantly higher levels and subsequently discovered 39 drug families that caused telomerase induction. Before these discoveries, it was uncertain whether telomerase activation in human cells was possible without the use of gene therapy, which has proven to carry an unacceptably high risk of cancer.

Astragalus Membranaceus

Another Georgetown study concludes that “subjects with the shortest telomeres had three times the incidence of cancer compared to patients with longer telomeres”. USA 89: 10114-10118. stress response. 5. et al.. Nat Genet 17(4): 498-502. HIV-positive patients display much shorter telomeres in the CD8+ T cells. Cell 43: 405-413. McClintock B. M.C. G. Watson. where 86 publications were evaluated and it was determined that “telomerase was not a cancer-causing oncogene and did not cause cells to lose growth control and become cancerous. A very powerful. Hypothetically. I don’t necessarily believe that people should live forever (most that I’ve asked wouldn’t want to anyway). Exp. J Cell Biol 90: 515-520. but also prolong the lives of those who already have cancer. Degenerative Disc Disease. Blackburn EH. S. Olovnikov AM. Alzheimer ’s disease and other degenerative diseases. (1965). al. Rudolph. (1995). Extension of life-span by introduction of telomerase into normal human cells. . et al. (1992) Telomere length predicts replicative capacity of human fibroblasts. (1941) The stability of broken ends of chromosomes in Zea mays. Geron Corporation. and cancer in aging telomerasedeficient mice. 9. A publication on these effects was released in 2010 by Sierra Sciences. (1999). This research may substantiate claims that keeping telomeres long through telomerase activation could both prevent cancer. Longevity.Science 269(5228): 12361241. 2. piece of information is that telomerase does not cause cancer. Szostak JW. 11. Funk. and argument-inducing. 37 (3): 614636. 239(94): 197-201.. J. R. J. Nat New Biol. The aforementioned studies excite me about the future of preventive medicine. Allsopp. Cell 96(5): 701-712. Müller HJ. Satya Ambrose Telomere Extension. Proc Natl. Doklady Akademii nauk SSSR.. Reconstitution of human telomerase with the template RNA component hTR and the catalytic protein subunit hTRT. Shampay J. The limited in vitro lifetime of human diploid cell strains. Blackburn EH. (1971) Principle of marginotomy in template synthesis of polynucleotides. References FOOTNOTES 1. Chronic Obstructive Pulmonary Disease. 201(6):1946-9. (1938) The remaking of chromosomes. et.. even in monozygotic twin studies when compared to their HIV-negative twins. (1981) Tandemly repeated C-C-C-C-AA hexanucleotide of Tetrahymena rDNA is present elsewhere in the genome and may be related to the alteration of the somatic genome. K. this may offer another very powerful option to us as primary care physicians. Calvin Harley at Geron Corporation published a review paper on the relationship between telomerase and cancer. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts.. Bodnar. D. but as far as reversing debilitating diseases. et al. L. & the Immune System Intro to Chinese Medicine Honors Project Rodney Billington June 17. et al. Collecting Net 13: 181-198. R. Sci. (1984) DNA sequences of telomeres maintained in yeast. 12. Blackburn.Dr. 8. Pruzan. 7. M. (1998). PhysioAge and the CNIO. Feng. 4. Gal. adding telomerase into the immune system holds promise of preventing HIV from ever developing into AIDS. 3. patients taking this were found to have fewer immune cells with shorter telomeres than they had at the beginning. W. 2012 After TA-65 had been on the market for almost 4 years.. (1997). Science 279(5349): 349-352.l J. S. L.Genetics 26: 234-282.. In 2002. 10. Ouellette. Hayflick. Further studies in the paper pointed out the shortened telomeres that are indicated in various different diseases such as cardiovascular disease. A. Cell Res. Astragalus. Acad. 6. Yao. L. but that cancer causes telomerase. D.C. Weinrich. Greider CW. Interestingly. E. Chang. (1972)Origin of concatemeric T7 DNA. TA Sciences. The RNA component of human telomerase. Nature 310: 154-157.

J. K. Telomere length and cognitive funciton in community-dwelling elders: Findings from the Health ABC Study.L. P. Telomerase expression restores dermal integrity to in vitro-aged fibroblasts in a reconstituted skin model. 19. M. J. 29.. 25. Tanglao. Schönland SO. R. W. Jiang. I. Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype. Cancer Res 69(4): 1604-14 24. EMBO Rep 2(9): 800-7 15. Am J Respir Crit Care Med 179(7): 566-571. (1999). risk of coronary heart disease. (2001). K. 21. M. (2008) The Discovery of C0057684. Funk. (1999). et al. (2000).Nat Genet 21(1): 111-114. al (2003). Lopez C. Lancet 361(9355): 393-5. Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Morales. Piatyszek."Telomere shortening in atherosclerosis. (2010). (2010). Singh. (2001). (2009). K.mice with short telomeres. Moore. E. Shawna.. Samper.-R. Association between telomere length in blood and mortality in people aged 60 years or older. (2001). S. Astragalus. Science 266(5193): 2011-2015 20. a Telomerase Activity Inducing Compound. Samani. 14.. C. & the Immune System Intro to Chinese Medicine Honors Project Rodney Billington June 17. et al. et al..... Telomere length. Telomere attrition in cancer cells and telomere length in tumor stroma cells predict chromosome instability in esophageal squamous cell carcinoma: a genome-wide analysis. J. et al. Harley. P. C. 16. et al. JAMA 304(1): 69-75.. R. Okuda. S.... Specific association of human telomerase activity with immortal cells and cancer. Reduction of leucocyte telomere length in radiographic hand osteoarthritis: a population-based study. et al. (2002). 2012 13. A. D.. G. et. Lancet 361(9355): 393-5. Tomás-Loba. Lancet 358(9280): 4723. Satya Ambrose Telomere Extension. buccal cells and brain tissue and its variation with ageing and Alzheimer's disease. L. Lindquist. Hu. Harley. Telomere length and risk of incident cancer and cancer mortality.. C. (2006). Proc Natl Acad Sci U S A. et al. X. R. White cell telomere length and risk of premature myocardial infarction. M. Telomeres and human somatic fitness.. G. Wang. Exp Cell Res 258(2): 270-278. N. Cawthon. Rejuvenation Res: Epub ahead of print. Holt. et al. K. Premature telomeric loss in rheumatoid arthritis is genetically determined and involves both myeloid and lymphoid cell lineages. Brouilette. Kim. O' Callaghan. Ann Rheum Dis 65(11): 1444-8. Telomerase Reverse Transcriptase Delays Aging in CancerResistant Mice. Le Maitre. (2008). A. Neurobiol Aging (Epub ahead of print). Hypertension 37(2 part 2): 381-5. M. (2008). K. Telomerase is not an oncogene. B. Shortened telomeres in circulating leukocytes of patients with chronic obstructive pulmonary disease. A Natural Product Telomerase Activator As Part of a Health Maintenance Program.. Telomere length in white blood cells. Arterioscler Thromb Vasc Biol 23(5): 842-6 30.. S. (2006). C. Smith. Savale. Smith. B. Chaouat. Telomere length as an indicator of biological aging: the gender effect and relation with pulse pressure and pulse wave velocity.. et al. 27. 23. Willeit. (2007). W. Thomas. A. (2009). K. Liu. et al. Accelerated cellular senescence in degenerate intervertebral discs: a possible role in the pathogenesis of intervertebral disc degeneration. 31. (2003). and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. 32. 28. 17. (2009). Association between telomere length in blood and mortality in people aged 60 years or older. Y.Arthritis Research and Therapy 9(3):R45 33. et al. P. N. N. 36. Brouilette. et al. Boultby. Lancet 369(9556): 107114.. 100(23):13471-6 . 35. Cawthon. R. (2003). et al. Mech Ageing Dev Epub 129(4):183-90 34. Aviv. J. 22. A. Cell 135(4): 609-622. C.. (2007). S. Flores. J. Restoration of telomerase activity rescues chromosomal instability and premature aging in Terc-/. et al. et al. Zheng. Flores. Zhai.. E. J Gerontol A Biol Sci Med Sci 61(8): 871-3 26. (2003). R. et al.Dr. etc. N. et al. K. Yaffe. et al. et al. et al. Jimenez. al. (1994).-L. Nat Genet 21(1): 115-118. Willeit. W. Oncogene 21(4): 494-502. W. A. Benetos. R. A. Aviv. The Methuselah Foundation (poster) 18.

Neurobiol Aging. Chen JJ. Callen E. Cellular senescence of angiofibroma stroma cells from patients with tuberous sclerosis. al. et al. 55. Chang. S. 52. (1997). Hum Mol Genet 11: 439–444. 51. 50. 38. Hum Genet. telomerase activity. Telomerase reverse transcriptase haploinsufficiency and telomere length in individuals with 5p. 44(7):1348-61.. (Epub ahead of print) 49. Thomas. L. B. L. 105(35):13051-6. (2007). Nat Biotechnol 18(1): 39-42. Short telomeres are a risk factor for idiopathic pulmonary fibrosis. 46. & the Immune System Intro to Chinese Medicine Honors Project Rodney Billington June 17. div id="ftn47"> 47. Telomere length. G. Ikeda H. N. Gerontology 56(4):390-403 42... Chavez E (2009). et al. 2010 Feb 4. and replicative potential in HIV infection: analysis of CD4+ and CD8+ T cells from HIV-discordant monozygotic twins. 39. (2008). Brain Dev 21(3): 184-91. al. H. Telomere length is associated with types of chromosome 21 nondisjunction: a new insight into the maternal age effect on Down syndrome birth. J. S. Kosmadaki. A. P. 44. (1999). Formation of functional tissue from transplanted adrenocortical cells expressing telomerase reverse transcriptase. Free Radic Biol Med. C. Aging Cell 6(5):689-97. 53. 48. al. Multani. 54. stress response. D. (2000). Vulliamy TJ. (2008). et al. L. and cancer in aging telomerasedeficient mice. Mech Ageing Dev.. (1999). A. al. Feingold E.. Samper E. M. Telomere length in leukocytes correlates with bone mineral density and is shorter in women with osteoporosis. Effros. (2010). 43. Telomeres and Immunological Diseases of Aging.-p. Palmer. M. N. et. M. R. The role of telomeres in skin aging/photoaging. et.Hepatology 48(1):186-95. Aids 10(8): F17-22. Exp Cell Res 258(2): 270-278.. Telomere shortening is associated to TRF1 and PARP1 overexpression in Duchenne muscular dystrophy. Yang. Telomere length in Hutchinson-Gilford progeria syndrome. Epub 2008 Aug 27. et. Satya Ambrose Telomere Extension. et al. Funk. Wang. Fujii. al (2010). et al. Toyoshima. et al. Andrews. 130(6):377-83. W. Weng. Ghosh S. (2008). Aguennouz M. Decker ML. Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia. Cell 96(5): 701-712. 2012 37.. Sasaki M. Biochimie 90: 122–130.Dr. Telomere shortening in the damaged small bile ducts in primary biliary cirrhosis reflects ongoing cellular senescence. (2008). et al. (1996). (2004). J Exp Med 185(7): 1381-1386. Prematurely senescent ARPE-19 cells display features of age-related macular degeneration. (Epub ahead of print) . Proc Natl Acad Sci U S A. B. Alder JK. Rudolph. et al. al. Vita GL. Chang. K.. et al. D. Shortened telomeres in the expanded CD28-CD8+ cell subset in HIV disease implicate replicative senescence in HIV pathogenesis. Telomerase expression restores dermal integrity to in vitro-aged fibroblasts in a reconstituted skin model. (2009). Nat Genet 36(8): 877-82. Valdes. A. Dyskeratosis congenita: the diverse clinical presentation of mutations in the telomerase complex. et. Micron 35(3): 155-159. R. Idol R (2007). Astragalus. Ohno.. Glotin AL. Richards. Longevity. 45.syndrome. S. Debacq-Chainiaux F. 41. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. (2002). Allsopp. M. Dokal I.Osteoporos Int 18(9): 1203-10. et. Gilchrest (2004). 2010 Jan 10. K. K. (2000). and B. Du HY. et. 40.

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