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

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