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How the world got lost on
the road to an anti-aging pill
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September 4, 2014: by Bill Sardi
I’ve written twice at ResveratrolNews.com about the idea of taking telomere-lengthening pills in hopes of achieving biological immortality, or at least living far longer. Telomeres are caps at the end of bundles of chromosomes. Telomeres shorten with advancing age which leads to instability of the entire genome (library of genes).
My first report in 2010 presented some pros and cons but summarily concluded that telomere-lengthening pills were not ready for prime time. [ResveratrolNews.com Oct 28, 2010]
Questions about taking telomere-lengthening pills continue to be received by this journalist. Regardless of the unconvincing science, telomere modification continues to fascinate longevity seekers.
When it first was found that cancer cells activate telomerase, the enzyme that repairs telomeres, and therefore helps cancer cells become immortal the idea of employing telomerase therapy was dismissed over a decade ago. [Science Dec 23, 1994] But telomere science continues.
And over a decade ago it was shown that telomerase deficient mice do not age prematurely. [Cell Oct 3, 1997] But again, science like that has not dampened public interest, especially consumers learning about telomeres for the first time.
My second report about telomeres reported that researchers had determined elevated iron levels shorten telomeres. [ResveratrolNews.com April 12, 2013] This is consistent with the overmineralization theory of aging that this writer has penned. [Longevinex.com Jan 2007]
So what more has been learned about telomeres and its repair enzyme telomerase since I last wrote on this subject?
Telomeres have been called “perfect sensors” of oxidation that damages DNA. Telomeres acquire DNA damage at a faster rate than other parts of the genome (library of genes).
It has been shown that the rate of telomere shortening is accelerated when cells are exposed to reactive oxygen species (ROS). [Free Radical Biology Medicine Jan 1, 2000] About 4.4% of the oxygen humans breathe turns into a destructive force that can damage cells and tissues. Natural internal antioxidants as well as dietary-acquired antioxidants counter oxidation.
So it should not be surprising to learn that a recent study shows that higher blood plasma concentrations of antioxidant nutrients such as lutein, zeaxanthin and vitamin C were strongly associated with longer telomere length in older humans (beta carotene, vitamin E and vitamin A were not found to be protective). [Journal American Geriatric Society Feb 2014]
Nor should it be surprising to learn that smoking and alcohol consumption, which deplete antioxidant nutrients, are associated with shortening and attrition of telomeres in humans. [Journal Gerontology A Biology Science Medical Science Feb 2014]
Likewise, adherence to the Mediterranean Diet is associated with longer telomeres and telomere repair (greater telomerase activity) among elderly adults. [PLoS One April 30, 2013] In further confirmation of that, 5-year adherence to a Mediterranean Diet reduced obesity and lengthened telomeres. [International Journal Obesity Research Feb 2014]
More intriguing is a study that compared elderly men in The Netherlands (northern Europe) with elderly men on the isle of Crete (southern Europe who presumably consume a Mediterranean diet). The Greek men’s telomere length was positively associated with production of internally-produced antioxidants (albumin, uric acid) rather than diet-acquired antioxidants such as carotenoids (lutein, zeaxanthin) or vitamin E. [Mechanisms Ageing & Development June 2012]
Theoretically the gene transcription factor Nrf2 that activates the production of internal antioxidants (glutathione, catalase and superoxide dismutase-SOD) should be the first line in defense to maintain telomere integrity.
Nrf2 is activated by biological stressors such as exercise, food deprivation, high altitude (lack of oxygen) or mild radiation (radon). For example, women who underwent exercise training for 6 months experienced a measurable rise in SOD activity, however their telomere length did not change significantly. [Mechanisms Ageing & Development May 2008]
Glutathione, considered the master cellular antioxidant that is internally produced in living cells via Nrf2, has been found to regulate telomerase activity in cells in a lab dish. When a chemical that depletes glutathione is added to cells telomerase activity decreased by 60%. So glutathione concentration parallels telomerase activity. [Journal Biological Chemistry Aug 13, 2004]
In one experiment mice were bred so they didn’t internally produce SOD but no shortening of telomeres was observed. [Journal Molecular Cell Cardiology April 2011] In fact, the restoration of telomerase activity in mouse cells animals that were bred so they didn’t produce telomerase restored the activity of catalase, an endogenous enzymatic antioxidant. [Free Radical Biology Medicine Nov 1, 2008] So the absence of telomerase activity increases activity of an endogenous enzymatic antioxidant.
Of added note, antioxidants in green tea and quercetin commonly found in red apple peel have been shown to prevent telomere shortening in lab animals. [International Journal Cardiology Jan 20, 2013]
Researchers conclude that it is telomere repair rather than the length of telomeres that determine health status among elderly adults. [PLoS One April 30, 2013] Telomerase, the enzyme responsible for maintaining telomere length, is not produced sufficiently to prevent shortening as telomeres erode with advancing age. [Ageing Research Reviews May 2014]
Shortening of telomeres emanates from repair mechanisms (telomerase) not being produced at levels sufficient to prevent telomere erosion and is believed to be irreversible. [Ageing Research Reviews May 2014]
When laboratory mice were treated with telomerase at year-1 and year-2 of life they experienced an increase in median lifespan of 24% and 13% respectively. [EMBO Molecular Medicine Aug 2012] While this achievement is notable and would equate to humans living an additional 7-14 years this is not the more demonstrative doubling of lifespan that is observed in lab animals given a calorie restricted diet.
Similarly, in laboratory mice, red wine and long-term resveratrol intake increases telomere length (6.5-fold) compared to laboratory mice fed normal chow without wine or resveratrol. Lifespan was unaltered, however. [Atherosclerosis Sep 2012]
A drawback of mouse studies like this is that telomeres in mice shorten ~100 times faster than human telomeres. But in general, shorter telomeres in mammals are believed to equate with longevity. Biologists have shown that the increase in the percentage of short telomeres rather than the rate of telomere shortening per month has been shown to be a predictor of lifespan in mice. [Cell Reports Oct 25, 2012]
Also, omega-3 oils have been associated lessening the rate at which telomeres shorten in humans with advancing age. [Nutrition April 30, 2014]
Additionally, higher concentrations of calcium and magnesium in blood plasma of older females (but not older males or younger adults) is associated with shorter telomeres. [Journal Nutrition Health Aging 2014] This finding reflects the loss of calcium from bone into the blood circulation with the onset of menopause and the decline in estrogen production.
However, there is a high variability among individuals in telomere length. Without a baseline study early in life it may be difficult to assess telomere status.
Some researchers theorize early-life oxidative stress that damages DNA and ends of chromosomes (telomeres) may be initiators of disease processes later in life. [Current Vascular Pharmacology Dec 18, 2013] Indeed, researchers recently reported that telomere length in birds (zebra finches) at their 25th day after birth is a strong predictor of realized lifespan. [Proceedings National Academy Science Jan 31, 2012]
Gender also plays a role in telomere length. Telomere length has been found to be longer in females than males. [Experimental Gerontology March 2014] Women generally live longer than males. However, telomere length has not been found to be associated with mortality among older men. [Experimental Gerontology Sept 2014]
Another complicating factor is that telomere lengths among elderly subjects were different in unrelated tissues (skin, joint tissue and white blood cells). [Mechanisms Ageing & Development Nov 15, 2000] Telomere length of leukocytes (white blood cells) is the most frequent tissue used in telomere experiments.
The question arises over whether so-called calorie restriction mimics in the form of resveratrol pills lengthen telomeres. As cited above, red wine and resveratrol were found to increase telomere length. Likewise, a limited calorie diet given to laboratory mice resulted in maintenance or elongation of telomeres. [PLoS One Jan 22, 2013]
Resveratrol, a molecular mimic of calorie restriction, has also been shown to increase telomerase the enzyme for telomere repair. [Chinese Medical Journal Dec 2011] However, resveratrol does not repair telomeres in malignant tumor cells, a fearful concern of biologists. [Journal Experimental Clinical Cancer Research June 2006; International Journal Oncology March 2006] In other words, resveratrol does not induce immortal cancer cells but rather castes them into a state of senescence wherein they cannot multiply. [Mechanisms Ageing & Development Aug 2009]
The science of ageing is still perplexing. With all that has been documented in this report so far, you would not expect to read that “stress-induced telomere SHORTENING increases longevity!”
Well, that is precisely what is being reported by researchers in Denmark. These researchers distinguish constant biological stress (oxidation) from stress-induced telomere shortening. It was the stress-induced telomere shortening that resulted in fewer mutations and longer life in cells in a lab dish. [BMC Systems Biology 2014]
So what is the average longevity seeker to make of all this recent science concerning telomeres? Should people who want to live longer undergo periodic blood testing to determine the length of their telomeres? Various reports have been written in an attempt to advise consumers about telomere testing. [EMBO Reports Sept 2011] A commercial telomere test is available online for $290. [Spectra Cell Laboratories]
A more convenient and economical way approach would be to determine telomere length indirectly. It turns out that telomere length is correlated with red blood cell width variation. The effect of telomere length on red blood cell width variation is comparable to the effect of smoking or alcohol consumption and is more significant in older adults. [PLoS One Dec 4, 2012]
Red blood cell width variation is a valid marker for mortality. This was discussed in an earlier report at ResveratrolNews.com. [ResveratrolNews.com Aug 26, 2014] and is worth re-reading. It has been known that red blood cell width increases with advancing age since 1972. [British Medical Journal Feb 26, 1972] There are 188 published reports showing red cell width variation predicts mortality dating back to 2004 with no contrary reports. That is more than can be said about telomere science and aging.
Red blood cell width variation tests are far more economical and widely available than telomere length tests. For those longevity seekers who must know if their health regimens are likely to result in a longer and healthier lifespan, the red cell width variation test is suggested. But granted, a telomere blood test appears to be more high science and fascinating than a common blood test. ©2014 Bill Sardi, ResveratrolNews.com
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