Telomere

“Telomeres shorten each time a cell divides. In most cells, the telomeres eventually reach a critical length when the cells stop proliferating and become senescent. But, in certain cells, like sperm and egg cells, the enzyme telomerase restores telomeres to the ends of chromosomes. This telomere lengthening insures that the cells can continue to safely divide and multiply. Investigators have shown that telomerase is activated in most immortal cancer cells, since telomeres do not shorten when cancer cells divide.” — National Institute of Aging

New health products are constantly appearing on the market in such numbers that I can’t hope to keep up. Product B was new to me. I was introduced to it by a doctor who said a family member was “quite enthusiastic” about its potential to “lengthen telomeres and thereby address a myriad of health issues.” Of course, I immediately asked “What exactly are they claiming Product B does?” and “Do they have evidence that it actually does what they claim?” Their website didn’t provide satisfactory answers.

Product B is described as “a powerful blend of complex botanicals and vitamins uniquely designed to offer superior telomere support for youthful aging.” It is sold as part of a multilevel marketing (MLM) scheme. Because it is classified as a dietary supplement, FDA regulations only allow them to make “structure and function” claims, so the claims are deliberately nebulous. Basically, they seem to be saying that short telomeres are bad (they cause aging and disease), telomerase is good because it makes telomeres longer, and Product B is an effective way to increase telomerase; therefore Product B prevents disease and retards aging. But these assertions are questionable, and the website doesn’t offer any credible evidence of clinical efficacy for any single health issue, much less a myriad of them. Or any evidence of safety, for that matter.

Oh, good grief! It’s sold by the Isagenix company. Talk about déjà vu! Isagenix keeps coming back to haunt me; it even generated my favorite insult ever: “Dr. Harriet Hall is a refrigerator with a head.” You can read the three articles I wrote about Isagenix here, here, and here.

If I am a refrigerator, at least I try to be a fair one. I wasn’t going to reject the claims out of hand just because Isagenix made them. I spent quite a bit of time searching the Internet for information, and I even wrote the company to ask directly for their evidence. They didn’t bother to reply.

One thing puzzled me right off the bat. Was there a Product A that I had somehow missed? Why did they name this “Product B”? That doesn’t impress me as a savvy marketing choice. Couldn’t they have thought up something catchier like “Telomiracle”? I couldn’t help wondering what the B might stand for and my mind quickly associated the words bogus, blarney, business, baloney, bunk, bullshit, blunder, basura (Spanish for garbage), barbaridad (Spanish for stupid thing), and blague (French for joke). It made me think of second choice, as in “plan B.” What does it make you think of?

Pardon the digression. It makes no difference what they call it. “A rose by any other name…” All that matters is what it is and whether it works.

What’s a telomere?

Every chromosome has a telomere, a repeated sequence of nucleotides at the end of the DNA strand. It is a disposable section that carries no genetic information. For vertebrates, the nucleotide sequence is TTAGGG; this repeats from 300 to several thousand times according to the species of animal. Telomeres are sort of like the aglet, that little hard piece on the end of a shoelace that keeps it from unraveling. They protect the end of the chromosome and keep it from losing important genes or sticking to other chromosomes.

When cells divide, each strand of DNA is copied. The enzymes that carry out that job don’t actually make a perfectly identical copy: when they get to the end of the DNA strand, they are unable to copy all the way to the very last nucleotide, so every time a cell divides, the DNA is shortened. Some of those TTAGGG’s are lost. When enough of them are lost, the cell is kaput. The Hayflick limit is the number of times a cell can divide before it becomes incapable of dividing further, typically 40-60 times for human cells in cell culture in the lab. If your cells stop dividing, you die.

Telomerase is a reverse transcriptase enzyme that has its own RNA. It serves as a template to make more TTAGGG sequences and add them to the telomere, reversing the usual shortening process. Telomerase is active in cells that can’t afford to stop dividing: embryonic cells, the testicular cells that produce sperm, and stem cells; but it is not found in most adult body cells. So the hypothesis is that if you could make the telomerase gene express itself in somatic cells, the telomeres might not shorten with age, the Hayflick limit might be over-ridden, the aging process might be stopped in its tracks, and we might overcome natural death and become immortal. So far, this hypothesis is only a dream.

Telomerase is not always a good thing

There’s a downside: encouraging telomerase might be dangerous. Cancer is characterized by unregulated growth, and telomerase is active in 90% of human malignancies. We don’t want cancer cells to live forever. Drugs that reduce telomerase activity are being investigated as cancer treatments. So if Product B really increases telomerase activity, that might not be such a good thing. We might fall from the frying pan of the aging process into the fire of more cancers.

The role of telomerase in aging is still controversial. Short telomeres could be just a sign of cellular age rather than a cause. In at least one species of seabird, they are neither: telomeres become longer with age.

The Product B website says “Almost every known disease can be attributed to the shortening of telomeres.” That is demonstrably false. Well, maybe they “can be attributed” by someone who is willing to make false attributions; but there is no evidence that short telomeres actually “do” cause almost every known disease. In fact, it has not been conclusively established that they cause any disease. There are correlations, but science is still trying to tease out causation.

Questionable information

The website doesn’t provide much in the way of scientific evidence, but it provides the usual testimonials and a couple of slick video presentations. Aging is a complex subject not well understood by science, and the science of telomeres is still in its infancy. They grossly oversimplify and misrepresent the science with sound bites like “We age because our cells age, and our telomeres get shorter.” They say we are born with 10,000 telomere bases, and when we get down to 5,000 bases we begin to die of old age. No, it’s not that simple.

The videos feature William H. Andrews, “a world-leading researcher on telomeres.” They call him “the principal discoverer of RNA and protein components of telomerase.” I was unable to verify that. He is not listed as one of the authors of this study that identified the protein composition of human telomerase.

Elsewhere on the web I learned that Andrews started out trying to develop a pharmaceutical drug that would activate the telomerase gene. He tested thousands of compounds in vitro; some of them worked but were toxic. After his research funding dried up, he met John Anderson, a “nutritionist” with decades of experience in formulating nutritional products. Anderson persuaded him to stop trying to develop a pharmaceutical drug, to just bypass the FDA and market a diet supplement instead. Together, they formulated a diet supplement product and accumulated lots of testimonials about more energy, sounder sleep, feeling younger, etc. Andrews says:

I have never seen so many anecdotal testimonies for any product ever. [He has obviously led a sheltered life!] I am a pharmaceutical scientist by training. I believe in double blind placebo controlled studies. I believe that placebo effects occur but I have just never seen this many testimonials before. I strongly believe something is happening but I am not going to make any claims until the clinical studies are done.

Sound familiar? Maybe he’s not making any claims, but the Isagenix company is certainly managing to get the Product B message across to its customers despite the required FDA disclaimer. I’d bet that most of their customers believe they are buying a product that will lengthen their telomeres, retard aging, give them lots of energy, and make them feel and look younger.

What’s in Product B?

You can read the list of ingredients here. Basically, it’s a mixture of four vitamins with a proprietary blend of some 30 herbal products such as thistle, horny goat weed, ginseng, and green tea. Most of these have never been shown to have any effect on telomerase.

This 2012 review article covered “Pharmaceutical Regulation of Telomerase and Its Clinical Potential.” They report that a commercially developed telomerase activator molecule, TAT2, derived from the root of Astragalus membranaceous has been found to transiently activate telomerase in the lab in T lymphocytes that were not proliferating. They say it “could” prove useful, but “more work needs to be done to determine mechanism of action and safety.” Neither TAT2 nor Astragalus are ingredients of Product B.

In Table 1 of that review, they list all the phytochemicals that are known to regulate telomerase. There are only 2 known telomerase activators and 7 known inhibitors. Several of the inhibitors are among the ingredients of Product B, which is being sold to activate telomerase. Something doesn’t add up. I can’t see any rationale for the particular kitchen sink of ingredients in Product B. It seems like they just threw in a little of everything anyone had ever suggested might be good for you.

The review concludes:

Pharmaceutically inhibiting telomerase may prove an important option in cancer therapy in conjunction with traditional chemotherapeutics. Conversely, the activation of telomerase could be useful to treat age related diseases and HIV/AIDS patients where lymphocytes have stopped proliferating. However, the long-term effects of regulating telomerase either positively or negatively are unclear.

William Andrews was one of the authors of this study that tested the Astragalus derivative TAT2 as part of a complex dietary supplement protocol. It activated telomerase in vitro, and in vivo it produced a decline in senescent toxic T cells and killer cells, mainly in subjects who were seropositive for cytomegalovirus (CMV). Mean telomere length did not increase, but they interpreted the results as positive because there was a reduction in the percentage of short telomeres. This was an uncontrolled pilot study by researchers who had a declared financial interest in the product, and it gives us no useful information about clinical benefits. William Andrews was one of the authors and he also served as a subject. The financial disclosure statement reports that he is founder and president of a company that develops therapeutics for inducing telomerase expression and that the study was partly financed by his company.

A single study of Product B

But TAT2 is not in Product B. I found only one study that actually tested Product B. It was a randomized, placebo-controlled double blind study but was small (only 43 subjects) and was presented at a conference but has not yet been accepted for publication in a peer-reviewed journal. It found that Product B increased catalase activity by 30% in red blood cells. That doesn’t tell us much. Why did they measure catalase instead of telomerase levels or telomere length? One of the authors explained, “There is yet to be a direct measure of telomeres that is reliable enough for an accurate measurement of telomere length for obtaining statistical significance in a clinical trial.”

That sounds to me like a poor excuse. It can’t be that difficult to measure telomere length, since so many studies have done it; after all, that’s how we learned that telomeres shorten with age. And I know there is an accurate method to measure telomerase: the TRAP method (Telomeric Repeat Amplification Protocol) that most researchers accept and that has been used in many other studies.

Isagenix is not the only company selling products targeted at telomeres. “America’s number one anti-aging pioneer,” Dr. Al Sears sells UltraEssence, described as a “reliable telomere support supplement.” And the Geron company sells Imetelstat to inhibit telomerase and treat cancer.

Conclusion

There are lots of proposed anti-aging remedies, and there are even Longevity Clinics, but as far as I know, no treatment has yet been proven to slow the aging process or extend the human lifespan. There are only preventive measures to reduce the risk of premature death and to improve the likelihood of staying healthy while you age (exercise, weight control, smoking cessation, vaccines, screening tests, seatbelts, treating high blood pressure, etc.).

I wouldn’t go so far as to call Product B a scam, but it certainly is not supported by good scientific evidence. It is based on bold extrapolations from basic research along with speculation, unwarranted assumptions, and wishful thinking. There are lots of products out there with similarly unproven claims, for instance Protandim, which I wrote about here, here, and here.

My Plan A: remain skeptical of Product B and wait for Evidence E.

 

 

Posted by Harriet Hall

Harriet Hall, MD also known as The SkepDoc, is a retired family physician who writes about pseudoscience and questionable medical practices. She received her BA and MD from the University of Washington, did her internship in the Air Force (the second female ever to do so),  and was the first female graduate of the Air Force family practice residency at Eglin Air Force Base. During a long career as an Air Force physician, she held various positions from flight surgeon to DBMS (Director of Base Medical Services) and did everything from delivering babies to taking the controls of a B-52. She retired with the rank of Colonel.  In 2008 she published her memoirs, Women Aren't Supposed to Fly.