An Update From Sierra Sciences: Cure Aging or Die Trying
Cure aging or die trying indeed - that is exactly the position in which we all find ourselves. The development of longevity science is a race, and not the good kind of race either; more the sort of race wherein a horror in the darkness is snorting behind you, and the consequences of failure are dire indeed. Worse, most of those running alongside you are oblivious to the beast that follows, and will not be woken from their daze. But this race we all win together, or we all lose, picked off one by one. There is no middle ground.
At the Sierra Sciences website you'll find an audio presentation from an anti-aging conference last year (I should note that I don't have a high opinion of such events, in which the frauds, potion-sellers, and scum far outnumber any serious presentations), and an update for 2010 on their work:
Sierra Sciences, LLC is a company devoted to finding ways to extend our healthspans and lifespans beyond the theoretical maximum of 125 years.Scientific research has shown that this theoretical maximum is limited because of the length of our telomeres which shorten as we get older. Our reproductive cells don’t experience this shortening, and thus don’t age, because they contain an enzyme called telomerase that re-lengthens the telomeres as they shorten. Sierra Sciences is searching for pharmaceuticals that will induce the production of telomerase in all our cells.
On November 6th, 2007 Sierra Sciences found its first telomerase inducing chemical; called C0057684. This chemical is the first ever discovered that activates the telomerase gene without killing the cells. Efforts are presently underway to learn everything possible about C0057684. But, in addition, C0057684 has provided Sierra Sciences with the first positive control ever for detection of telomerase gene activity in normal human cells. This has served as a very powerful tool for the development of robust high throughput screening assays for finding additional telomerase inducing chemicals. As such, in the last year Sierra Sciences has discovered an additional 62 chemicals that activate the telomerase gene. This now enables the scientists at Sierra Sciences to design better chemicals with increased potency and specificity. Additional screening for even more chemicals is also underway.
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We have screened 186,704 compounds. We have found 555 telomerase inducers. These represent 33 distinct drug families. Most potent compound = 6% of goal. We are screening 4,000 compounds per week.
I have written on Sierra Sciences in the past. You might stroll back into the archives to see what I had to say. In general I'm not sold on the theory that telomere length is in fact a limit upon life span, versus it being a secondary marker for the progression of numerous other processes that limit life span. Maybe it is a strongly contributing root cause of aging, maybe it isn't - but there are only two ways to find out for sure. Firstly, more research, and secondly try the telomere lengthening and see what happens. If the fastest path to a confident resolution for this uncertainty is accomplished by initiatives like Sierra Sciences, then more power to them.
The problem with lengthening telomeres with telomerase is that this is exactly what many cancer cells do to get around the limit of cell proliferation set by the limited length of telomeres.
I have a suspicion that just lengthening telomeres would cause a higher incidence of cancer.. potentially much higher. The research is important, however, and should be tested in mice to see what happens. I doubt this is the silver bullet, as you likely agree.
I don't think telemere extension therapy will increase the incidence of cancer. Ways to increase telemere lengths in mice have been developed that do not cause cancer.
However, why do we think telemere shortening, in and of itself, is a cause of aging? I think its more of a bio-marker than a cause. Telemere lengths seems to be a regulated function. Whatever causes the regulatory mechanism to fail, allowing the telemeres to shorten, is the underlying cause of aging, not the telemere shortening itself. At least that how I see it.
I'm an employee of Sierra Sciences; however, I'm not on the scientific staff, and I don't speak for the scientists.
However, to answer kurt9's question, there are several reason we believe telomere shortening is a fundamental cause of aging. One of the most compelling is the paper by Bodnar, et al., "Extension of life-span by introduction of telomerase into normal human cells," Science, 1998. In that experiment, scientists at Geron Corporation inserted the telomerase gene into normal human cells.
As most of you probably know, there is a limit to the number of times our cells can divide before they senesce - the so-called "Hayflick limit." What this team found is that hTERT-positive human cells did not observe the Hayflick limit; they continued to divide indefinitely.
In other words, it's already established that you can essentially immortalize a human cell by activating telomerase. The question is whether this also applies to organisms.
But there are some compelling reasons to believe that it will. A follow-up experiment in 2000 at Geron demonstrated that when you take elderly skin cells and grow them on the back of a mouse, you see visibly old skin; when you then telomerize those cells and grow them on the back of a mouse, you see visibly young skin.
Further, to address Dan C's point about animal testing, perhaps most exciting of all is a 2008 experiment at Maria Blasco's lab at the CNIO in Spain; Blasco's team found that, by overexpressing telomerase in mice, they could create a strain of mice that lived 40% longer and were still completely youthful and healthy at the point the control mice were losing their dexterity.
Of course, mice don't age in exactly the same way as humans, and Dr. Blasco's techniques would not work on an already-living organism, so there's no way to move this technique into clinical trials - but it's an important demonstration of concept.
At Sierra Sciences, we wouldn't assert that telomere shortening is the *sole* cause of aging, but we do believe that the science is very clear that it's a fundamental cause of aging, and we think any permanent cure for aging is absolutely going to need to include a mechanism for maintaining telomere length.
Recently met with Dr Bill Andrews at the Rock N Roll marathon Las Vegas, talked to him briefly about Knee problems. Looking for knew techniques on how to walk or even run
This research makes me very excited. I'm not a scientist, but I have a strong background in science, and from the data that I've seen, I'm confident that this is a necessary step to fight aging (probably the most important one). It boggles my mind that more people are not investing in this and helping Sierra Sciences reach their goals. I will gladly fund this research when I have the financial means to do so, which will hopefully be soon.
Last weekend on New Year's Day, I drawn a few pictures of my vision to reverse Aging on our Human Bodies, the Cell Scrubber can flush out old blood cells and keep healthy ones in the bloodstream, and the Rejuvanator can turn a senior into a 30 year-old again. If I save enough money and invent it, I could win the Nobel Prize and change the World.
I have managed to identify approximately 160 telomerase activators
at http://greenray4ever.com/lifexnotes3b2.html#TAALPHABETICSELECT .
These telomerase activators have different modes of producing telomerase activity. Some of them are transcriptional inducers of hTERT, others
phosphorylate hTERT for return from the cytoplasm to the nucleus, or
impact hTERT transcriptional activity indirectly, rather than through interaction with the hTERT promoter.