test your knowledge
How the world got lost on
the road to an anti-aging pill
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October 28, 2010: by Bill Sardi
A molecule extracted from the botanical herb Astragalus is now being widely touted as a “youth preserver.” One advocate calls it “the most exciting breakthrough in the last century.” Theoretically, how does this molecule do this? Answer: By lengthening the age-shortened end caps of chromosomes called telomeres.
A published human study claims those subjects who took the Astragalus extract called TA-65 had cells that were 5-20 years younger. TA-65 activates the gene that produces telomerase, the natural enzyme that repairs fragmented telomeres.
There always a kernel of truth to such claims, but in this instance there is also a lot of stretching the truth too.
Telomeres are known as the biological clock of the cell, since they shorten with each cell division and with advancing age. Shortened telomeres is claimed to govern the rate of aging. Telomere lengthening agents like Astragalus extracts would theoretically slow aging.
However, studies reveal that telomerase-deficient mice do not age prematurely. The correlation between telomere length and mortality is poor. The length of telomeres in white blood cells decreases with advancing age, but in the Zutphen Elderly Study, telomere shortening did not relate to mortality among men over age 70.
Contrary to what was anticipated, when laboratory researchers intentionally shortened telomeres in yeast cells (considered a model of aging), this actually led to a significant extension in life.
In another baffling study, biologists observed that the telomeres of certain sea birds tend to lengthen as they age!
Is telomere shortening a cause or an effect? Telomere length could just be a marker for aging, or for disease such as cancer, but then again, it may not even be a reliable marker.
Rita B. Effros of the David Geffen School of Medicine at the University of California, Los Angeles, recently called telomeres “the canary in the coal mine.” Dr. Effros says while shortened telomeres have been documented in a wide variety of pathologies associated with aging and are also predictive of early mortality in the very old, shortened telomeres are “not the cause of mortal effects… but rather the harbinger of increased health risk.”
Dr. Effros points to old T-cells (thymus cells) with shortened telomeres that exhibit an impaired ability to fight viruses and secrete large amounts of inflammatory agents. She goes on to say that maintenance of high levels of telomerase by telomerase activators not only retards telomere loss but “also restores a more youthful function” to T-cells.
Take note longevity seekers, Dr. Effros is not talking about longevity, she is talking about health, and the two do not automatically correlate with each other.
For example, laboratory animals fed a normal-calorie diet plus high-dose resveratrol, a widely promoted an anti-aging molecule, were profoundly healthier but they did not experience an extended lifespan. (However, a much lower dose of resveratrol appears to more closely mimic a life-prolonging limited-calorie diet, particularly when accompanied by other molecules such as quercetin, rice bran IP6 and ferulic acid. Such a low-dose botanical mix switched 630 of 832 longevity genes in the same direction.) Health and longevity may be mutually exclusive of each other.
The most recent report shows there is a relationship between shortened telomere length and cancer mortality. But there is not scientific consensus over the relation between telomere length and cancer.
The idea of lengthening telomeres with molecular activators is a muddy area in biology. Another potential problem posed by telomerase activators is that they may promote cellular immortality, which is the hallmark of tumor cells. Cells need to age and die off (senesce). Telomere shortening facilitates cellular aging which may possibly lead to chromosomal instability and the initiation of cancer. On the other hand, telomerase activators may stabilize telomeres in tumor cells, facilitating tumor growth.
Furthermore, the dual role of telomerase in cancer is doubly confounding. In a telling laboratory study, mice had their telomerase disengaged, which resulted in telomere shortening, and this subsequently reduced survival even though telomere shortening strongly inhibited liver tumor formation.
Tumors often activate an alternative mechanism that lengthens telomeres, probably in a defensive manner. However, patients with these tumors that have converted to this alternative form of telomere lengthening have a very poor prognosis.
Ironically, when telomeres in tumor cells are intentionally shortened to magnify the effect of radiation treatment, tumor cells respond in a defensive manner and their telomeres do not become shorter even though telomerase is deficient.
Measurement of telomere shortening to diagnose cancer has been disappointing. It appears that telomeres shorten only after the diagnosis of cancer. Therefore it cannot be used as a predictive indicator.
There is some discussion that telomeres and telomerase both “ignite” or “restrain” stem cells, and therefore inhibit cancer and delay aging. However, both activation and inhibition of telomerase may occur to produce favorable health.
It is interesting to learn that telomerase is activated by oxygen starvation (hypoxia) which is another hallmark of tumor cells.
Some researchers argue that cellular senescence via shortening of telomeres is an anti-cancer mechanism, even though it is associated with progressive aging. The very idea of lengthening telomeres may run contrary to biological design.
Not all telomerase activators exert favorable biological responses. For example, cotinine, the main metabolite of nicotine, activates telomerase but also causes the growth of abnormal cells. Another example is, genistein, found in soy, which has been shown to activate telomerase in mouse prostate cancer cells but also augments the growth of these cells.
Resveratrol, a red wine molecule that is heralded as a molecular mimic of a calorie-restricted diet, which is known to double the lifespan in various living organisms, and to have strong anticancer properties, has been shown to inhibit telomerase activity in breast cancer cells in a laboratory dish
In another study, resveratrol induced telomere instability, but in doing so, it also inhibited abnormal cell growth and the death of tumor cells.
There are other ways to increase telomerase without taking pills. A 3-month regimen of eating a diet low in fat and refined sugars and which in whole grains and plant foods, increased telomerase in the blood by 29%!
Vitamin D: In a comparison of low and high vitamin D blood serum concentration in adult humans, those individuals with the highest vitamin D levels were spared 5 years of telomeric aging.
Green tea: EGCG (Epigallocatechin gallate), found in green tea, has been shown to inhibit telomere shortening in heart muscle cells (cardiomyocytes). This may be beneficial or deleterious, depending upon which researchers one consults. Another study shows the exact opposite: EGCG induced telomere fragmentation. This was demonstrated at very high concentration only. This may indicate dosage defines whether polyphenolic molecules found in tea leaves, spices, grapes, berries, etc., are beneficial or problematic.
Omega-3 oils: In another study, adults who consumed the greatest amount of omega-3 oils experienced a 5-year reduction in telomere shortening.
Estrogen: The number of years that women produce natural estrogen appears to increase telomere length and decelerate cellular aging.
The generation of oxygen-free radicals is also known to shorten telomeres and antioxidants which reduce oxidation in the mitochondria (power plants) of cells appear to inhibit telomere shortening. Some mitochondrial antioxidants are magnesium, N-acetyl cysteine, lipoic acid, and many others.
A drawback of the astragalus study was that it did not have a control group to compare results. Furthermore, after 12 months of taking astragalus extract, the mean telomere length did not increase, however there was a significant reduction in the percent short telomeres. This is what generated all the hoopla over TA-65. Two patients in the study reported experiencing anxiety reactions, possibly indicative that this pill over-inhibited TNF, an anti-inflammatory agent naturally produced in the human body.
Of interest for those who follow the over-mineralization theory of aging, the provision of iron to rodents increases telomerase activity by 3-fold even though there is no change in telomere length in rodent liver. It could be that increase telomerase activity prevented telomere shortening, but it certainly didn’t lead to lengthening.
Apparently copper-induced oxidation plays a role in accelerating the shortening of telomeres at a critical site on DNA.
In confirmation of the over-mineralization theory of aging, shorter telomeres are associated with the accumulation of calcium in coronary arteries. Low meat consumption (low iron intake), high fruit and vegetable consumption, and low coronary artery calcification, correlate with longer telomere length.
Does all this sound confusing to you? The jury is still out on how to interpret telomeric changes in human chromosomes. This doesn’t sound like telomerase activators are ready for prime time. The online spammers are out in full force to promote Astragalus extracts as the next fountain of youth. However, what is currently being promoted is pseudoscience. #### Copyright 2010 Bill Sardi ResveratrolNews.com