In 2001, Geron Corporation isolated a chemical compound they called TA-65 from the Chinese herb astragalus in its efforts to find compounds that activate and inhibit cellular generation of telomerase. Telomerase is an important enzyme that repairs degradation to the ends of DNA strands known as telomeres. In fetal cells and stem cells, telomerase keeps the DNA strands in a condition to divide without degradation.
But in most cells, telomerase is not active and each time a cell divides into two new cells, the resulting new cells have shorter telomeres. Eventually, the telomeres get so short that some cells can no longer divide, a condition known as senescence. But along the way, some of the cells with ever-shorter telomeres may divide improperly causing genetic mutations such as missing or damaged genes.
Short Telomeres Break Cell Functions
TA-65, it turns out, does boost telomerase production in at least some human cells, enabling them to make their telomeres grow a little longer. The effects has been likened to turning back a biological clock that limits cell reproduction.
Senescence turns out to be advantageous for stopping cancer cells — if, that is, the cancer cells can’t keep growing their telomeres longer. Many cancer variants, around 90%, feature uncontrolled replication of cells into tumors that will not stop growing because such cancer cells pump out high levels of telomerase that allow them to reproduce without end by averting senescence
Shortening telomeres at first glance appear they would help avoid this. But it turns out that short telomeres may induce cells to become cancerous in the first place as replication with short telomeres is more likely to cause mutations that might trigger cancerous behaviors.
Now, in a study just published in the Journal of the American Medical Assn., Austrian researchers reported that people with shorter telomeres are more likely to develop cancers.
The researchers measured telomere length in the leukocytes (a type of white blood cell) of 787 people in 1995. The scientists sorted the people into three groups based on their blood cells’ telomere length: longest, middle and shortest.
Over the next 10 years, 92 developed cancer. The researchers found that the risk of cancer was twice as high in the middle-length group compared with the longest-length group. It was three times higher in the shortest-length group compared with the longest-length group.
This makes sense, the authors wrote, given that telomeres keep chromosomes stable and cancer is associated with rearrangements of chromosomes that can result in some genes working overtime and others not at all — causing cells that shouldn’t proliferate to begin multiplying out of control.
Thus there is an intrinsic confusion as to whether lengthening telomeres may in some cases enable damaged cancer cells to divide out of control when they might have been stopped by the telomere aging mechanism. Bill Andrews, a researcher who formerly worked at Geron and takes TA-65 himself, explains the dilemma:
Very recently, remedies have been developed that could possibly alleviate, abolish, or reverse this “up to now” inevitable fate by activating an enzyme called telomerase, which may help maintain telomere length. One such remedy, a nutraceutical called TA-65, is already commercially available and several people have already signed up to benefit from its potential to extend health span and life span.
Unfortunately, this remedy also carries with it a potential for promoting cancer. And so, we are brought back to the age-old question, “Do you give a risky cure to a dying person, or do you simply let the person die because the cure is too risky?” Every one of us is suffering from this disease, but most of us are in only the very early stages and have the luxury not to make this choice so hurriedly. However, many of the people in the later stages of aging feel that they don’t have this luxury and choosing to take TA-65 may be what they feel to be their only recourse to “saving” their lives. Should these people be deprived? Should they be allowed to intentionally increase their risk of cancer to potentially enhance and prolong their health span and life span? We should let people who are concerned about their age-related deterioration, whether or not in the later stages of aging, decide for themselves.
Andrews believes that when all risks are considered, pumping up telomere length may help avoid cancer and isn’t likely to do a lot to help cancer grow as most cancer cells already have plentiful supplies of telomerase. It’s a calculated gamble, one that this expert thinks he understands well enough to make the choice to use TA-65 on himself.
Telomerase Activators Help Rebuild Telomeres
Geron Corporation scientists believe that understanding how to control telomeres and telomerase is likely useful, even essential, to fighting many types of cancer. The company was more interested in treating cancer than aging, something that it views as possibly meaning telomerase inhibitors may be more important than activators.
In 2007, it licensed the TA-65 compound to a company called T.A. Sciences that was started by a man named Noel Patton who was an investor in Geron. Patton was fascinated by the growing understanding of the aging process and wanted to apply this research to products that people could actually use. The result is the “Patton Protocol” featuring TA-65 supplements to help wind back the biological clock in many human cells by causing the body to pump out and apply more telomerase to repairing the ends of DNA strands. This help many cells grow their telomeres a little longer, adding more years of possible cellular reproduction that some believe will enable longer human life.
The Cost of TA-65
Although the cost of the “Patton Protocol” featuring TA-65 supplements and telomere testing to verify effect has declined a bit from the initial $25,000 to $35,000 over two years, it is still quite expensive. The company has revised its pricing model, now selling the TA-65 supplements apart from testing and other supplements in 6 month segments at varying dosage levels that cost from $1200 to $4000 per six months. But even with this somewhat lower unbundled pricing, TA-65 is still very expensive.
Is TA-65 A Scam?
Some think that TA-65 seems like a scam. They point to “snake oil” products of the past and the outrageous cost of the supplement versus the inexpensive astragalus plant from which it is derived as evidence of scam-like pricing.
Both criticisms are missing the point. TA-65 was discovered by Geron and it is a legitimate company. Its findings regarding TA-65 were useful even if there was never any attempt to make a product out of it. Multiple studies and research papers show that TA-65 does increase telomerase activity and lengthen the telomeres of some cells, so there is little doubt that it at least does do what its most basic claim is.
Geron continues to identify and synthesize telomerase activators, meaning that they do believe these compounds are going to be important and useful. Earlier in 2010, they announced an experimental model using a new telomerase activator they call TAT153 for treating mice with a lung tissue disease known as Idiopathic (i.e., unknown origin) Pulmonary Fibrosis (IPF). There are no drugs available to date to treat this disease, but TAT153 looks like it works in mice and so there’s promise it may work in humans, too.
Inflammation precedes and is associated with fibrosis of the lung. Study animals showed a 40% decrease in inflammatory cells in the TAT153-treated group. Histology showed less extensive fibrosis preserving a greater proportion of functional lung tissue in treated animals. The study included measurements of lung function in TAT153-treated animals and controls. The TAT153-treated animals showed a 30% increase in lung compliance (elasticity) and a 30% decrease in airway resistance (mechanical factors which limit the access of inspired air to the alveoli, or air sacs) compared to controls, demonstrating a significant attenuation of functional deterioration. These positive effects of TAT153 in the mouse model of pulmonary fibrosis were associated with an approximately two-fold increase in telomerase activity in lung tissue samples.
From the limited description in the research press release, it sounds like TAT153 is chemically synthesized, rather than extracted from plants like TA-65. But Geron continues to work on plant-derived telomerase activators, too, reportedly moving along in the development of another compound from astragalus known as TAT2 as a treatment for HIV and AIDS.
The current manufacturing process for the supplement requires massive amounts of astragalus to get tiny amounts of TA-65, consequently making it expensive. The limited demand for TA-65 also means the overhead for making it has to be distributed across fewer customers, thus keeping prices high.
It’s a little like comparing a Porsche with a Kia. The Porsche is way more expensive, in large part because there are relatively few customers but also because it is arguably a far better car. The differences in price and number of customers doesn’t mean that Porsche is a scam nor that Kia is the best deal. Similar arguments apply to TA-65.
Given the rapid advancements in biochemical manufacturing in recent decades, if there really is a demand for telomerase activators then it seems reasonable that some company will come along and find a way to make them much less expensively, perhaps by modifying bacteria via genetic engineering to make them pump out telomerase and/or telomerase activators at much less expense. The full text of a study on TAT2’s effect on the replication and functionality of human CD8 T lympocytes (a type of white blood cell in the human immune system) explains that antiviral activity was improved and telomere lengths increased somewhat.
Geron’s involvement with TA-65 hasn’t ended, either. In September 2010, a research study on the effects of TA-65 involving staff from Geron, TA Sciences, Sierra Sciences, and other organizations was published. The study focuses on the effects on immune system cells and has some particularly interesting findings that TA-65 significantly reduced the number of cells with very short telomeres without affecting the mean length of telomeres. The effects were more evident in people with chronic viral infections such as CMV (cytomegalovirus) which affects about half the US population, with a lower percentage of young people and a higher percentage of older people affected. The study observed that people with CMV infections appear to have about 10 years more “telomere aging” than those without CMV infections based upon CD8 T cell telomere length measurements. This seems to be the direct result of the immune system cells replicating many more times to fight viral infections and over time suffering from more rapidly depleted telomeres.
Alternatives to TA-65
There are some potential competitors for TA-65. It is clearly not the only telomerase activator around, nor is telomerase the only way to lengthen telomeres.
Two other compounds derived from astragalus, Cycloastragenol and Astragaloside IV both are claimed to act as telomerase activators and are sold as nutritional supplements. Reportedly Cycloastragenol is the same compound as Geron TAT2. Both are significantly less expensive than TA-65. Rumors are that TA-65 may actually be mostly Cycloastragenol, but TA Sciences has kept quiet on this topic.
Recent studies on the benefit of multivitamins suggest that they cause a slight reduction in the rate of telomere shortening over many years. In particular, it appears that vitamins B12, C, and E are responsible for the reduced rate of telomere degradation.
Some cancer cells, around 10%, do not rely upon telomerase to maintain telomere length. They have other means to do this called ALT (Alternative Lengthening of Telomeres) that as yet are poorly understood. It is possible that products could be developed to boost telomere lengths based upon these mechanisms after they are understood better.
One of the challenges of using TA-65 or other telomerase activators is that many of the people who are interested in them are already taking supplements that inhibit telomerase but have other beneficial health effects. In particular, there are claims that resveratrol, curcumin, quercetin, melatonin, green tea and its extracts, garlic (particularly its component alliicin), silymarin (from milk thistle), and cat’s claw products all exhibit an inhibitory effect on telomerase activity.
Some advocate not taking any of these other supplements while you are taking TA-65, Cycloastrogenol, or Astragaloside IV supplements. Others advocate alternating between them on a weekly or monthly basis. Still others suggest that spacing them several hours apart may be enough to maintain the telomerase activation benefits. Unfortunately, it’s likely that it will be a long time before anybody can point to conclusive studies on interactions between these compounds.
Shortened Telomeres Just One Sign of Aging
Even if you could afford TA-65 or an alternative, it appears to only directly target one factor in aging. Besides shortened telomeres, there are many other components of aging, including oxidation, protein and lipid glycation, mitochondrial damage, hormonal imbalances, and other common aging problems from which nearly everybody suffers. While there are strong reasons to believe that increasing telomere length will allow healthy cells to replicate for years or even decades longer, if the other aging factors are not addressed then it may not be enough to make much difference in the lifespan of an entire organism even if individual cells can live much longer.
Other Anti-Aging Tactics
Improving your health and slowing your aging are good goals. But I’d recommend that you need to do some testing to find your main problems areas before pouring a lot of money into supplements. Even if TA-65 or its competitors works really well, they alone are not going to be enough to give you stellar health and longevity.
Common Essential Tests
The routine medical tests you get from a typical doctor are totally inadequate for understanding your overall health. You should at a minimum get a good cholesterol profile (VAP or NMR, not the regular one that only estimates LDL cholesterol rather than measuring it), hormone testing for estradiol (an estrogen), testosterone, pregnenolone, and DHEA, CBC (complete blood chemistry) with fasting so you get a fasting glucose measurement, fasting insulin, thyroid tests (free T3, free T4, TSH), CRP (C-Reactive Protein) which is a good inexpensive test for inflammation, homocysteine, fibrinogen (affects blood clotting), and vitamin D.
Attain Optimal Vitamin D Levels
Almost everybody is deficient in vitamin D. It is a very inexpensive supplement, I’d strongly recommend everybody consider a good multivitamin and vitamin D to be among the mainstay supplements they use. Take a look at my articles Flawed Calcium and Heart Attack Study Misleads Consumers and Adjusting Your Vitamin D Intake to Optimal Levels for information on how to figure out how much vitamin D you need and why you need to take it with vitamin K, calcium, and magnesium to keep calcium from building up inside your arteries and veins. The US RDA for vitamin D for most adults is only 400 IU, but achieving optimal levels likely requires 2000 IU or more each day. Some people may need even over 10,000 IU per day, the upper limit on what is regarded as generally safe based upon several recent studies. The extreme variability is what makes testing vitamin D levels in blood so important to getting the dosages right.
Increase Your Omega-3 Fatty Acid Consumption
Most Westerners get too much omega-6 fatty acids and too little omega-3. I strongly recommend supplementing with at least 600mg per day of omega-3 fatty acids EPA and DHA, preferably 1200mg per day. This would take from about 2 to 4 typical low concentration fish oil softgels or 1 or 2 higher concentration fish oil softgels. Some people, especially vegetarians, use omega-3 in the ALA form from plants, but you need about 10 to 20 times as much ALA to get the same effect. You can read more about selecting omega-3 supplements in my article Selecting An Omega-3 Fat or Fish Oil Supplement. Don’t just buy based upon cost — many of the cheapest supplements also come with a lot of extra calories and cholesterol, ironic considering they are often suggested as a remedy for elevated LDL cholesterol levels.
Block Damage from Glycation and Diabetes
Other things you should look into are glycation inhibitors, particularly if you have high blood glucose. L-Carnosine, benfotiamine (a fat soluble version of vitamin B1), and pyridoxamine or P5P (pyridoxal 5 phosphate) are all helpful for reducing the damage from glycation, a process in which sugars attach to and damage proteins and fats in the body. Many regard diabetes as being in part a form of accelerated aging caused by rapid glycation and oxidation. Having long telomeres isn’t going to help much at avoiding this kind of damage.
Fight Inflammation and Blood Clots
A good set of anti-inflammatory supplements is also helpful. Bromelain and curcumin are good basic choices. If your fibrinogen and/or CRP tests are not optimal, then nattokinase is often helpful for improving these. Serrapeptase is another anti-inflammatory that is also reputed to help with clots and congestion.
I’d strongly advise you that if your doctor suggests you take warfarin (Coumadin) to reduce the risk of blood clots, you should either learn about the severe health risks from that drug and educate your doctor on alternatives including protease compounds like nattokinase and bromelain and other nutrients with clot-inhibiting effects such as high dosage vitamin E and omega-3 fish oils. Don’t let your doctor talk you into taking warfarin and avoiding vitamin K. Vitamin K is essential for keeping calcium in the bones where it belongs. If you don’t get enough of it, you may find yourself suffering from rapid development of atherosclerotic plaque with high concentrations of calcium. Essentially, the inside of your blood vessels start to harden as if they are growing bone.
Quench Free Radicals
Antioxidants are very important to stopping the damage from free radicals travelling around the body. Vitamin C is a mainstay, of course. Be careful to take most of your vitamin A as beta carotene which the body will convert to vitamin A as needed. Too much pre-formed vitamin A blocks the effect of vitamin D and causes other health problems. Get a balanced vitamin E supplement which includes more than just alpha tocopherol that cheap vitamin E supplements use. If you only take the alpha form, it displaces gamma tocopherol from the body and actually is likely to worsen oxidation damage. So take plenty of the gamma tocopherol form, preferably more gamma than alpha. If you can afford them, also take tocotrienols and sesame lignans as both complement the typical vitamin E tocopherols.
Lower Blood Lipids
If your LDL cholesterol and triglycerides are high even after starting omega-3 at 600mg to 1200mg per day, then boost your omega-3 further and look into using niacin, plant sterols, red yeast rice, and fiber supplements to help lower them.
Avoid statins if you can, they cause far too much reduction in the body’s generation of the important CoQ10 enzyme. As red yeast rice does this to a lesser degree, you can add in a CoQ10 supplement (preferably the ubiquinol form) to replenish the stores of this critical enzyme and antioxidant. CoQ10 deficiency is a serious problem as it contributes both to oxidative damage throughout the body and a reduction in the number and function of the mitochondria that are essential for powering cells. The symptoms of it often show up as muscle pain, muscle weakness, confusion, low energy, and extreme fatigue. Doctors should be aware of these symptoms being connected with low CoQ10 levels given the widespread use of stating drugs, but unfortunately most seem ignorant or unwilling to order CoQ10 tests.
Ensuring Thyroid Sufficiency
Many people have low thyroid output as they age and this has been tied to other health problems including weight gain, high cholesterol, depression, anxiety, and elevated C-reactive protein. Doctors often use only the TSH test to judge thyroid function and use antiquated references ranges to evaluate test results. Free T3 and free T4 tests should be used along with TSH. Some people may also need other thyroid tests to look for less common problems.
Nutritionally, the two major obstacles to adequate thyroid hormone levels are insufficient iodine and tyrosine. Thyroid hormones are built from tyrosine combined with multiple iodine atoms. Both deficiencies can be addressed with inexpensive supplements. The US RDA for iodine is 150 mcg per day, but this is probably inadequate for full health. Japanese populations that eat seaweed and other seafood products typically are consuming in excess of 1000 mcg per day, sometimes even far in excess of 5000 mcg per day. Iodine deficiencies are a growing problem as people eat less salt and some salts are not fortified with iodine:
The public health message to limit salt use underlies a gradual and insidious return of iodine deficiency. The National Health and Nutrition Examination Surveys (NHANES) assessment of Americans’ health revealed a 50% reduction in iodine levels and a quadrupling of iodine deficiency in the period between 1971 and 1994. Twelve percent of the population surveyed from 1988 to 1994 were severely iodine deficient, judged by urinary levels of iodine.8 Women of childbearing age are at particular risk for iodine deficiency, with up to 36% evidencing low levels.9
For most people, 1000 mcg of iodine is probably a good target. If you add tyrosine supplements, consider taking them early in the day as some people report they may cause restlessness if taken at night.
Restore Youthful Hormone Balance
Adjusting your hormonal levels is rather complicated, far more than a few paragraphs could cover. It also varies markedly between men and women. What’s common for aging humans, regardless of gender, is that most people have declining DHEA levels as they age and many also have other problems with their sex hormones becoming unbalanced.
In particular, aging men tend to have way too much estradiol (a form of estrogen) and not enough testosterone. This combination causes a vicious cycle of growing fatter which leads to fat cells making more aromatase which forces testosterone to be converted to estradiol which encourages even more fat buildup. Women who have too much testosterone can have similar problems, but this is probably less common than the high estrogen and low testosterone problem that is an epidemic in aging men.
Wacked out sex hormones are responsible for a lot of health problems. They can cause or greatly contribute to cardiovascular disease, depression, obesity, diabetes, and metabolic syndrome. It is actually not unusual for an aging obese man to have more estrogen than a healthy pre-menopausal woman. While this is fine for her, the results for him are disastrous. But most doctors don’t even begin to address such problems. Instead, they spend lots of effort on trying to fight symptoms that are often significantly influenced by the hormone imbalances they are ignoring.
See the reading list below for a few articles on male and female hormones that do a good job of explaining common problems and how to fix them via testing, supplements, and medicines.
No Magic Bullet for Anti-Aging Medicine
Slowing down aging and improving health isn’t something that can be done by any one practice, supplement, or medicine. If you’re serious about it, you have to address a plethora of common problems. This article suggests several common areas to address in addition to whatever you decide to do or not to do about slowing down the shortening of your telomeres. A much more comprehensive treatment of the topic that includes more discussion not only of supplements but also of lifestyle and food is available in Ray Kurzweil’s highly rated book Transcend: Nine Steps to Living Well Forever.
Another anti-aging science book that has been getting strong reviews is David Stipp’s title The Youth Pill: Scientists at the Brink of an Anti-Aging Revolution. It focuses primarily on recent anti-aging research involving supplements and medicine, a tighter focus than Kurzweil’s much longer book. You can read a sample of the first chapter of the book below.
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