Humans have dreamed about immortality for as long as there have been humans. Yet the “fountain of youth” is still just a myth, and human lifespans today are topping out around 120 years for a few people. People over age 100 are one of the fastest growing age groups, but still there are grave concerns about whether large numbers of centenarians will be healthy enough to be worth the additional years.
Scientist and author Dr. Aubrey de Grey recently wrote about the advancing anti-aging technologies and why they may work in his book Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. De Grey believes that human lifespans of 500 years or more may be just around the corner. But there are many different competing theories of aging, each explaining different aspects of aging but none of which individually explain it all.
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Telomere Theory of Aging
One of those theories of aging has to do with the ends of our DNA strands known as telomeres. Telomeres get shorter with age, kind of like a biological clock within each of our cells. When telomeres get very short or disappear, cells can no longer reproduce well. Either their reproduction stops, or DNA replication misfires and causes genetic damage.
There is evidence that reversing the shortening of telomeres could significantly increase lifespan, at least at the cellular level. For instance, most cancer cells are immortal in that they can reproduce endlessly because their telomeres do not shorten.
Recognizing the promise of the telomere theory of aging and what restoring telomere length might do to lifespan, investors have funded companies to find a way to apply the science to marketable (and they hope eventually profitable) aging treatments. One of these companies is T.A. Sciences. It has announced the TA-65 telomerase activation supplement derived from the Chinese herb and traditional medicine astragalus.
If you’ve got the money (about $25,000 to $35,000 spread over two years) and are willing to undergo the full four segments of the Patton Protocol of pulsed TA-65 administration and consume many other helpful dietary supplements (antioxidants, N-acetylcysteine, alpha lipoic acid, lycopene, lutein, trimethylglycine [betaine HCl], CoQ10, L-Carnosine, EPA, DHA, etc.), the company believes that it can restore your cells to a youthful state. They are confident enough of its safety that all of their employees age 40 and over receive the Patton Protocol TA-65 treatment, named after the founder of T.A. Sciences, entrepreneur Noel Patton. Noel Patton takes twice the dosage of TA-65 per day as anybody else, in effect making him a human guinea pig for the supplement.
Note that TA-65 isn’t an FDA approved treatment. As the company explains, it is not a drug and they don’t claim it prevents or treats diseases so therefore FDA approval is not required:
TA-65 is classified as a nutritional supplement, not a drug. TA-65 activates telomerase and this helps keep cells functioning in a normal and healthy way as we age. It is not a drug and we make no claims that it prevents or treats any disease. FDA approval is not required for nutritional supplements.
Why Do Cells Age?
Before you spend a fortune on a therapy like this, you are likely to want to know what it does, why is it believed to work, and what are the risks. To explain why it may work, let’s rewind to 1961. Dr. Leonard Hayflick, a noted biological researcher, discovered that normal human cells can only replicate a limited number of times before they can no longer reproduce.
About 30 years later, Dr. Calvin Harley discovered the connection between cell division and aging is that DNA strands get shorter with each replication. He noticed that the ends of the strands look like a bunch of repeated junk that doesn’t have an obvious purpose as part of genes. The ends were called “telomeres” and as it turns out, the lack of obvious genetic purpose is far from accurate. Telomeres allow DNA strands to be replicated without damaging the essential DNA between them. They function as starting alignment points for DNA replication to begin. However, the starting point of the telomere is not itself replicated, thus each successive generation of cells has shortened telomeres.
When telomeres get too short, the cells can no longer replicate well or at all and become senescent. The Hayflick limit is the number of times cells can divide before senescence occurs, and it varies from species to species. In humans, it is about 70 times in a 3% oxygen environment similar to the inside of the human body. Surprisingly, some organisms do not have telomeres that shorten with age. The small bird known as Leach’s Petrel has an unusually long lifespan for birds its size with an average of 20 years and maximum recorded lifespan of 36 years. In 2003, scientists discovered that the bird’s telomeres lengthen with age, possibly explaining its long lifespan.
However, it has been noted that humans have some of the shortest telomeres for primates yet have among the longest lifespans. Similar observations have been made regarding bird species that live longer than Leach’s Petrel. Clearly there is something more involved in lifespan than just telomere length. It’s possible that some species have non-critical genes at the ends of their chromosomes that aren’t as badly damaged by replication misfires due to lack of telomeres. Or it could be that the DNA repair capabilities of some species are better and make it possible to fix the mess of damaged DNA that resulted from telomere-depleted cells attempting to replicate. As of yet, there is mostly speculation and little consensus on this matter.
Australian-born biologist Elizabeth Blackburn‘s groundbreaking work on telomere research while at the University of California is recounted in the book Elizabeth Blackburn and the Story of Telomeres: Deciphering the Ends of DNA. She is co-discoverer of telomerase, the enzyme that helps lengthen telomeres. She has continued her research on telomerase, discovering that the enzyme upregulates 70 genes known or suspected to be involved in the growth of cancers in the body and that people under high stress tend to have shorter telomeres.
Interestingly, other research has shown that poor people tend to have shorter telomeres than rich people, potentially making them more susceptible to more rapid aging and cancer induced by telomeres becoming so short that DNA replication goes haywire and causes mutations, cross-linking, and other genetic defects. The poor people tended to have telomeres shorted by the equivalent of about 7 to 9 years of additional age.
TA-65 Increases Telomerase Production
T.A. Sciences licensed the TA-65 molecule from Geron which originally developed it during cancer research trying to find ways to stop cancer by interfering with the uncontrolled cellular replication of cancer cells. Most types of cancer cells are immortal, meaning they can continue to reproduce endlessly. This is because they, like many stem cells, have the unusual property of reproducing without shortening of their telomeres.
Claimed Evidence for Effectiveness of TA-65
In 2002, T.A. Sciences purchased a license from Geron for non-pharmaceutical and cosmetic uses of TA-65. In 2005, the company ran a small double-blind study involving 36 research subjects over 24 weeks. 12 of the subjects consumed placebo tablets, and 24 consumed product tablets.
T.A. Sciences has also published many testimonials from customers. Some of them point to testing showing that subjects gain about 100 base pairs added to their telomeres for each 3 months of treatment. At birth, human blood cells typically have telomeres about 8000 base pairs long. By around age 35, they are down to about 3000 base pairs. And in the elderly (age 65 and up), telomere length falls below 1500 base pairs.
If you work out the rate of telomere shortening per year from age 35 to 65, it appears to be about 50 base pairs per year. So if TA-65 supplementation is adding about 400 base pairs per year, it is “undoing” about 8 years of aging per one year of treatment.
What would the benefits for longer telomeres be? As University of Utah research Dr. Richard Cawthorn has found, people with shorter telomeres have much higher death rates:
Cawthon’s study found that when people are divided into two groups based on telomere lengths, the half with longer telomeres lives five years longer than those with shorter telomeres. That suggests lifespan could be increased five years by increasing the length of telomeres in people with shorter ones.
People with longer telomeres still experience telomere shortening as they age. How many years might be added to our lifespan by completely stopping telomere shortening? Cawthon believes 10 years and perhaps 30 years.
Another telomere-related health study cited by the Los Angeles Times clams that the cardiovascular disease patients with the shortest telomeres had twice the risk of heart failure and death of those with the longest telomeres:
One recent study published in the July 2008 Journal of Arteriosclerosis, Thrombosis and Vascular Biology, an American Heart Assn. journal, found that, among 780 patients with stable heart disease, people with the shortest telomeres in their immune cells had twice the risk of death and heart failure after 4.4 years as patients with the longest telomeres. Those in the highest-risk group had telomeres half the length of those in the lowest-risk group.
Getting a useful quantity of TA-65 requires processing literally tons of astragalus plants, thus in part explaining why this therapy is expensive. Astragalus is widely used in Chinese medicine and has been for more than a millenium. As a derivative of a widely used herbal supplement with a very long track record of usage, it is perhaps somewhat less likely that any of the substances in it would be severely harmful to humans.
Eventually, it is likely there will be a way to produce the TA-65 substance more efficiently. However, if TA-65 really works, it seems the demand would skyrocket. Therefore the price may not come down even if it can be made more inexpensively.
One possible risk is that there may be something else in the TA-65 supplement coming from astragalus that is harmful to humans. But the track record of astragalus usage is long and the herb has increasingly been studied for immune-boosting effects entirely apart from TA-65’s telomerase activation effect. So it seems at least somewhat likely that harmful effects of small quantities of other astragalus compounds would have been noticed in other studies, but this is by no means a certainty.
A bigger risk may be cancer. Cancer cells use telomerase to lengthen their telomeres and reproduce without limit. Thus some have speculated that increasing the amount of telomerase in the human body could render people more susceptible to cancer. So far, there is no compelling evidence of this. Some of the theories on how cancers form relate to telomere-depleted cells attempting to replicate and getting damaged in the process, thus turning them into cancer cells. If that line of reasoning is correct, keeping the telomeres longer could be advantageous to avoiding the development of cancer cells in the first place.
Telomerase Activation Competition
T.A. Sciences isn’t the only company in the business of activating telomerase to extend cell telomeres. One of the co-discoverers of the telomerase gene, Dr. William H. Andrews, co-founded Sierra Sciences in 1999 to find compounds to acts as telomerase activators. It has developed technology to rapidly screen thousands of compounds for the telomerase activator properties. The company claims to have discovered 176 such telomerase activating compounds so far and is screening about 4000 more compounds each week. Sierra Sciences has also published a list of diseases that it believes are related to cell senescence that could be treated with telomerase activation technology.
Sierra Sciences isn’t ready with a product yet. So its founder, Dr. Andrews, is taking TA-65 from his competitor:
Telomere biologist Bill Andrews of Sierra Sciences is taking a telomerase-boosting supplement called TA-65. “I believe it’s safer than driving my car to work,” he says. Since he started taking it a year and a half ago, Andrews says he has moved from the back of the pack to the front in 100-mile runs known as ultramarathons.
He’s provided a testimonial for T.A. Sciences, too:
“Last weekend I finished in 11th place overall out of 72 runners in a 100 mile ultramarathon. That’s the best placing I ever had. Surprisingly, I had no pains whatsoever after the race. I felt like I had done just a typical afternoon jog.
I am a Telomere Biologist, and I understand how important a telomerase activator could be in countering the aging process, but I don’t understand the mechanism of how lengthening telomeres would give me this sudden success in running. Maybe TA-65 does more than just lengthen telomeres.”
Bill Andrews, PhD 56
Several companies besides TA-Sciences are selling other astragalus extracts claimed to activate telomerase similar to TA-65. In particular, Astragaloside IV and Cycloastragenol are two of the more commonly sold alternatives. Some claim that Cycloastragenol is about 10 times more potent at activating telomerase than Astragaloside IV.
Speculation is that TAT2, another astragalus extract being researched by Geron for its telomerase activation properties, probably is chemically identical to Cycloastragenol. Rumors are that TA-65 may have significant Cycloastragenol content but TA Sciences disputes this however won’t explain the exact composition of TA-65.
There are reports from the life extension community that a certified lab analysis was performed on October 19, 2010, by American Analytical Chemistry Lab on TA-65 8mg capsule and they found the ingredients included 5.44 mg of cycloastrogenol and 0.27 mg of astragaloside IV. Based upon this report, the speculation that cycloastrogenol is the main active ingredient in TA-65 has increased.
TA Sciences has started to resell TA-65 through distribution channels. RevGenetics is now selling TA-65 as a replacement for its previous Astral Fruit product. They discontinued their Astral Fruit product around the time when Geron Corporation got a patent on telomerase activation. TA Sciences is a license-holder of Geron Corporation, so possibly RevGenetics believed it would be legally safer to resell TA-65 given the newly issued patent. But at least one employee of their company has stated publicly they are working on developing a new formulation of Astral Fruit and in the meantime are selling TA-65 as they verified in the lab that is does have significant telomerase activiation capabilities. They also believe that TA-65 is cycloastragenol based upon their lab analysis, despite TA Sciences statements to the contrary.
Ethical Debate Regarding Life Extension Technologies
In 1994, Hayflick wrote a book How and Why We Age that explained his theories on aging. Interestingly, he’s against life extension technologies and considers them immoral and fraudulent, as explained in his position paper from 2002 that was originally published in Scientific American in June 2002.
Scientist Dr. Aubrey de Grey is skeptical of telomerase activation being the key to life extension and says its benefits have yet to be proven. But in contrast to Hayflick, he argues that basic anti-aging science is already well ahead of the funding for it to be applied to humans. He believes that the first human to live to 1000 years old may already be alive today. To help jump-start the application of anti-aging sciences to humans, he created the Methuselah Foundation’s Mprize for researchers who demonstrate methods to break the record lifespans for mice. As mouse studies are often precursors to human studies, the hope is that demonstrating the means to extend mouse lifespan will make it more likely that similar research will be conducted in humans.
Even if human lifespan isn’t extended remarkably beyond the current record of 122 years, improving health quality during old age would be a dramatic achievement. If typical 90 year olds had the health of today’s 40 year olds, spending on health care could be controlled while life expectancies continue to increase.
Physicians Ronald Katz (senior editor of Longevity magazine, found of the American Longevity Research Institute) and Robert Goldman have written The Official Anti-Aging Revolution: Stop the Clock, Time is on Your Side for a Younger, Stronger, Happier You to explain the various theories of aging and many of the available anti-aging medicine technologies and how they prevent aging-related diseases and lengthen lifespans. They believe it will soon be common for people to live beyond 100 years old, but that health and lifespan are diminished in most people due to vitamin and mineral deficiencies, hormone imbalances, stress and sleep troubles, and other maladies of increasing age that cause more severe health problems.
They describe how vitamin and herbal supplements can help remedy nutritional deficiencies and toxin accumulations, natural hormone therapies can address falling levels of human growth hormone, DHEA, melatonin, thyroid hormones, and sex hormones estrogen, progesterone, and testosterone that all contribute to common problems such as obesity, diabetes, and cardiovascular disease. It’s a very comprehensive book with emphasis on scientific basis and avoiding sensationalism.
The telomere theory of aging is just one of many, but it does explain several aspects of aging and lifespan that don’t seem to be fully explained by other theories. Personally, I think telomeres shortening with age is likely a significant part of the overall aging process, but there is more to it than just telomeres.
That said, it is unlikely that TA-65 is the “fountain of youth” on its own. But from the evidence presented by T.A. Sciences, it does appear that TA-65 increases telomere lengths significantly and does cause improvements in some measurable criteria for health. The two downsides are the very high cost and a risk of side effects. So far, with about 100 patients undergoing TA-65 treatment to date, apparently there are no known significant side effects.
It is notable that many of the patients undergoing TA-65 treatment are scientists and doctors. Partly this may be because they have the money to do it, but it seems likely they also are more likely to be aware of the telomere aging theory and its implications.
Ultimately, understanding whether telomerase activation technologies like TA-65 will significantly improve health and lifespan is going to take decades and many more subjects before any really solid conclusions can be reached. If T.A. Sciences and Sierra Sciences can cut the price of telomerase activation therapy so they can enroll more customers in carefully monitored treatments with objective measurements of wide ranges of health parameters, it seems plausible there may be definitive answers about the long-term promise of telomerase activation within the next decade.
TA-65 and similar technologies are definitely something to watch. If I had the money to participate, I would give it a try myself as you only commit to 6 months at a time and if there are no positive results or harmful side effects, you can drop out before the full 24 months of treatment.
However, even if I did have the money, I’d still be very interested in other developments in anti-aging medicines. Fortunately, many of them are much more financially affordable and even the not-so-rich can try to extend their healthy lifespans through combinations of supplements, hormones, exercise, and anti-stress/pro-sleep lifestyle changes.
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