RevGenetics Blog
Resveratrol and Telomere News
4January2012
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Since the discovery of DNA as the genetic material of all living organisms, fundamental dogma in biology states that the pecking order of control of cellular molecules puts DNA in front. DNA passes the information next to RNA, and RNA finally passes the genetic information to proteins. With this in mind, scientists have been studying how DNA is regulated, changed or mutated and how these DNA modifications ultimately lead to protein modifications. Since it is proteins that make up the bulk of a cell’s structure and carry out desirable cellular functions and undesirable ones like aging, understanding how DNA is regulated is needless to say very important. Case in point, SIRT-1, a protein that promotes many of the health benefits associated with extension of lifespan in various organisms, has been proven to regulate the DNA sequence of key longevity DNA genes. Specifically, in 2008 a group of scientist published the observation that human fibroblast cells artificially made to express more SIRT-1 delayed the onset of aging on those cells. SIRT-1 is a protein that can modify and therefore regulate DNA. That same study also provided clues into which cellular pathways may be involved but not a mechanism for how cellular life extension actually takes place. Fast forward to the present. In what is very exciting news, an article accepted but yet to be published, a group from Japan led by Yoshinori Katakura has repeated some of those experimental observations but very importantly added a potential explanation for the mechanisms for the delay in aging in human fibroblast cells (Biochemical and Biophysical Research Communications, 2011). In this new article, the researchers overexpressed SIRT-1 protein via three methods. First, they genetically modified the cells by introducing an extra copy of SIRT-1 gene (which causes more SIRT-1 protein to be made), second, they treated the cells with resveratrol (which also causes more SIRT-1 protein to be made) and finally, they starved the cells (this method also causes more SIRT-1 protein to be made). Of these three methods of SIRT-1 up-regulation, it is fortunately that resveratrol alone was sufficient to replicate the observed results since this method is not insulting to our body when compared to the other two methods. The results from the researchers similar to what had been published before, observed that the more SIRT-1 protein present, the longer the cells grew and the more the aging features of these cells was delayed. Furthermore and demonstrated for the first time in fibroblast cells, the extra SIRT-1 protein present in the cells caused specific RNA needed for telomerase protein to be made. In essence these authors conclude that the extra SIRT-1 protein induced by resveratrol (and by other methods) leads to more telomerase protein being made. And given the fact that telomerase protein activity has been shown to be sufficient to cause normal human epithelial cells to replicate indefinitely, a mechanism for cellular life extension is pushed forward. Yet another bit of information for strengthening the case in establishing the importance of understanding how DNA is regulated and how this can lead to tangible practical results.
This entry was posted in Telomere News
Telomere News
16December2011
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In the early 1990’s it was discovered that the reason human cells become “old” and are unable to continue growing like they do when they are “young” was due to shortening of the ends of the DNA regions called the telomeres. As it was first discovered in other organisms and then in humans, the telomeres shorten every time the cell undergoes cell division. When a critical telomere length is reached, a signal was created that would then stop the cell from replicating, at this point the cell was referred as senescent.
However, many questions remained for example, what exactly was causing the signal that actually stopped the cells from replicating, what proteins were involved and could these signals be stopped or reversed. Since then many proteins involved with regulating telomere length have been discovered, most notably telomerase, which can directly extend the telomeres.
However, a remaining question from this early research was the observation that humans have 23 chromosome pairs (i.e. DNA) and each has a different telomere length. Could it be possible that a single chromosome shortening stop the cell from dividing or would it be a combine signal from a few or all chromosomes?
These questions were finally addressed by a research group from Australia and published in the journal of EMBO reports (EMBO reports, December 2011, pages 1-8).
The authors discovered that five telomeres that had reached critical length were required before the signals associated with senescence were triggered.
This research may seem trivial given the fact that methods of extending telomeres exist. But when one is reminded that historically research on aging was viewed as trivial because of its inevitability and now is an active area of research. This research may point to the importance of looking for specific telomerase activators that target the shortest of telomeres and delay the aging of our cells.
This entry was posted in Telomere News
Resveratrol News
16December2011
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Resveratrol is a natural compound that works as a chemopreventive compound as many pre-clinical trials have demonstrated. Ongoing studies have given vast amounts of information to the pharmacokinetics of this compound.
Most of those studies have been done in cells or tissues where dose ranged from 10-5 to 10-4 M concentrations. In itself, these concentrations may be useful for a researcher to know but can be difficult to interpret into practical dosages for the average person. Therefore, several questions remain to be fully addressed. For example, what is the most suitable dose of resveratrol for effective cancer preventive intervention on a person?
This and other questions are discussed in recent scientific articles and simple straightforward answers remain elusive. In a recent article, a group of scientist led by Andrea Gescher discussed our current understanding of this topic and concludes that more research is needed to understand the pharmacokinetics of resveratrol (Molecular Nutrition and food Research, 2011).
In another review article by Thomas Walle from Medical University of South Carolina the bioavailability, adsorption and metabolism of resveratrol is discussed (Annals of the New York of Academy of Sciences, 2011 pages 9-15). Although this article provides more general information with regards to dosages, for example during initial resveratrol studies 25 mg of resveratrol were given in studies trying to emulate the dosage provided with the intake of red wine. Interesting, this article points out how researchers logical approach of increasing the dosage to increase the chemopreventive beneficial effects of resveratrol does not lead to more resveratrol in the blood stream.
They suggest that this may be explained by the fact that we might not know exactly what resveratrol is interacting with that gives us these benefits. In addition, Dr. Walle discusses that resveratrol may be changed into one of its analogues (a resveratrol-like structure) that actually may be imparting the health benefits.
Interesting, some of the concerns that Dr. Walle comment with regards to adsorption are also addressed in another article this month (Journal of Agricultural and food Chemistry, 2011 pages 12352-12360). In this research article, the authors address the adsorption by nanoencapsulating resveratrol. The authors conclude that nanoencapsulating of resveratrol lead to higher chemical and antioxidant activity suggesting that nanoencapsulating resveratrol not digested in the gastrointestinal tract leads to better adsorption.
This entry was posted in Resveratrol Studies
Resveratrol News
22November2011
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Obesity is a major problem in Western cultures since it increases the likelihood for diseases such as diabetes, cardiovascular diseases, cancer and osteoarthritis. A straightforward solution may be to eat less, in what is referred in the scientific community as caloric restrictions. It is well documented in various animal and cell models, that a 30-50% caloric restriction can not only reduce the incidence of cancer and diabetes but also improve stress resistance and decelerate other age-related functional declines such mental abilities.
What is remarkable about caloric restriction is that once the body gets used to the lower calories, physiologically it functions in a more efficient matter and acquires an improved metabolic profile. These observations and others have led to studies with the objective of looking for compounds that can mimic caloric restriction without actually cutting calories.
Resveratrol is one such compound. Resveratrol’s capacity to activate the same proteins that are also active when animals or cells have undergone caloric restriction has been remarkable. However, although many studies have been done on human cells few studies have actually been done on humans.
In a current study published in the journal Cell Metabolism, the researchers did exactly that (Cell Metabolism 2011, Vol. 14 page 612). The researchers gave obese people (but who otherwise did not suffer from any other condition), a dietary supplement of trans-resveratrol over thirty days and then examined several physiological parameters among them, whole body energy expenditure, fat storage, and the ability of fat tissue to breakdown fat molecules.
Remarkably the data showed that like caloric restriction, in thirty days resveratrol was able to lower energy expenditure, improve metabolic profile and improve general health parameters (such as decreases in glucose, insulin and triglyceride concentrations in the blood).
This entry was posted in Resveratrol News
Telomere News
22November2011
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Many studies have established that stress to your body can lead to a depletion of your immune cells. Unfortunately there are many forms of stresses that our bodies must endure during our lifetime ranging from psychological distress, poor diet, smoking and a sedentary lifestyle.
All of these aforementioned psychological and behavioral stress factors have also been documented to cause telomere shortening to our immune cells, the leukocytes.
In a recent paper, a group of researchers led by Elizabeth Blackburn published in the Journal of Aging Research that sleep deprivation also contribute to the shortening of telomeres of our leukocytes (Journal of Aging Research 2011 October 20).
The authors hypothesized that shorter sleep duration and quality would cause sufficient stress to shorten our telomeres in our leukocytes. The researchers aims were to document sleep duration and quality in healthy women between the ages of 50-65 years and then measure the telomere length obtained from blood draws. The procedure followed divided the sleep patterns into fairly bad, fair, fairly good and very good sleep.
The difference in telomere length between fairly bad and very good was statistically significant. This study provides preliminary evidence that telomere length may provide a link between sleep deprivation and age-related diseases. Fortunately for all of us, sleep is a modifiable health behavior, so get a good night sleep your telomeres will appreciate it!
This entry was posted in Telomere News
Resveratrol News
5May2011
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Glioblastoma multiforme (GBM) is one of the most aggressive tumors with a very low median survival rate of 14.8 months. Sadly it is also the most common primary brain tumor.
Although multiple studies have been done on this cancer few have yielded good results in large part due to the brain barrier’s ability to select out therapeutic chemicals. So efforts to ameliorate the disease are welcomed, even if they involve baby steps in the direction of more efficient treatments and increased patient survival rate.
In a recent publication aimed at maximizing therapeutic treatment and determining the molecular mechanisms of resveratrol has on GBM, resulted in favorable outcome (Journal of Cellular Physiology 2011 April online).
In the research article the investigators systematic approach first involved establishing the function and needs of the GBM cancer, in this case the cancer needed the activation of a protein called STAT3. They then demonstrated in both animal and cell models that treating with resveratrol in combination with radiation increased the likelihood of the cancer cell dying. As far as the mechanism, they determined that STAT3 was inhibited by this combination treatment.
Bottom line, survival rated was significantly improved. A good baby step in the right direction.
This entry was posted in Resveratrol Studies
Telomeres Tested – A TA-65 Study
29April2011
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It is now common knowledge in the field of aging that telomere dysfunction is associated with many age-related pathologies. What remains to be discovered is the “how” of these mechanisms so that we can then better treat these age-related pathologies.
In an extremely interesting research article in the journal Aging Cell led by investigators Maria Blasco and Calvin Harley, the investigators demonstrated that telomerase activator TA-65 elongates telomeres and increases health span of old mice without increasing the cancer incidence (Aging Cell March 2011, pp 1-18).
TA-65 is a small compound purified from the root of Astragalus membranaceus, which is capable of activating telomerase enzyme that in turn elongates the telomeres. It is the maintenance of telomeres that is critical for cellular function and longevity of many cell types. In this study the investigators specifically demonstrated that TA-65 worked only through the activation of telomerase, and this activation of telomerase led to increased telomere’s lengths when supplemented in the mice’s diet.
More importantly, this supplement leads to improved health as indicated by glucose tolerance, osteoporosis and skin fitness without increasing the cancer incidence. Of significance is the fact the researchers only fed the mice for 4 months and observed reversal and improvement of selected mouse tissue.
This is one of the few studies in an organism that demonstrates consuming TA-65 from the Astragalus plant can lead to dramatic increases in overall health.
Update: 12/2011
RevGenetics has brought in a professor and UCLA visiting scholar to Test TA-65. Because of our testing at RevGenetics, we can confidently state that we have verified telomerase activation. We therefore certify TA-65 for telomerase activation in human cells. Because of our independent testing we have started making it available to our customers here: (Buy TA-65). We ask you to purchase this product directly from RevGenetics to help support independent research, and verification of product claims.
This entry was posted in Telomere News
Resveratrol, Brain Cancer and Arthritis
18March2011
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Malignant glioblastoma is currently a difficult cancer to treat because its ability to diffuse, rate of recurrence and resistance to treatment. As the most prevalent type of brain tumor, glioblastoma has the worst prognosis of a central nervous cancer with medial survival rate of 14 months.
In a current study published in the journal of agricultural and food chemistry (J agric Food Chem (web) March 2011) a group from Italy, conducted experiments to determine the anticancer properties of resveratrol on a human glioblastoma cultures. The results of their experiments determined that resveratrol was able to stop the growth of the tumor cells and limit the ability of the cells to migrate.
In addition to these findings the researchers observed that once the cells were treated with resveratrol the protection lasted four days. These observations collectively support the possibility of using resveratrol to be administered in the chemotherapy regimen of these cancers. Giving a little more hope ways to treat this deadly cancer.
In another study published in the same journal, resveratrol was used to treat arthritis (journal of agricultural and food chemistry (web) March 2011). In their study, this group compared other stilbenes (analog molecules similar to resveratrol) and their ability to treat arthritis. In the study, the method that researchers used to measure anti-inflammatory arthiritis effects was measuring the compounds involved with inducing inflammation. They observed that by a combination of various stilbenes they were able to decrease the inflammation due to arthritis.
This entry was posted in Resveratrol News, Resveratrol Studies
Resveratrol Dose By The Annals of the New York Academy of Sciences
3February2011
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Occasionally scientific journals will ask leading scientist to write reviews that in their opinion highlight the most important discoveries on a subject of interest. A new series of articles have been recently published by the Annals of the New York Academy of Sciences highlighting the many functions of resveratrol (Volume 1215, Resveratrol and Health).
We have selected a few of these articles and briefly reviewed those articles that may be of relevance to individuals taking resveratrol. The first of these articles deals with resveratrol and its effects on cancer mechanisms (pages 1-8). The article does a very good job at describing some of the pathways that are important for resveratrol’s anticancer properties.
For example, the authors go over the data that clearly indicates that apoptosis (a method of killing cells) is important for chemoprevention which is enhanced by resveratrol. (There is another article that specifically addresses the apoptotic properties of resveratrol on pages 79-88). Equally important is the conclusion they make which is what many have suspected all along: “resveratrol hold [a] tremendous potential as an efficient anticancer drug of the future”.
This article is followed by a review on our current understanding of the bioavailability and metabolism of resveratrol with an emphasis on humans (pages 9-15). Interestingly, this article also discusses the resveratrol analogs that may help improve bioavailability of resveratrol to our cells. On this note, there is an article (pages 131-137) that discusses clinical data supporting the uptake of 450 mg/day.
The next article (pages 16-21), deals with the cardioprotective effects of resveratrol. In short, the coronary heart disease is one of the leading causes of death in the United States and for Western cultures. The strengths of this article may be the section where the authors discuss the many proteins specifically targeted by resveratrol, such as NQO2, and suggest a framework for uncovering how these proteins are aided by resveratrol.
Another article in this compendium that also discusses cardioprotective effects but takes a different angle is on pages 117-122. However, in this article the authors emphasize more the vascular system as a whole and then how resveratrol’s anti-inflammatory properties may be the mechanism for preventing or reducing the vascular aging in the elderly. In short there many interesting article in this collection that merit some reading.
This entry was posted in Resveratrol News, Resveratrol Studies
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