Of flies and worms: is the science behind the benefits of resveratrol in peril? - Pittsburgh Medical Technology | Examiner.com

A research study published a week ago in Nature will shake the credibility of the research that supports the notion that sirtuin-2 is an anti-aging gene and also challenge the view that resveratrol extends the lifespan. Today's study published in Nature was spearheaded by Dr. David Gems from the Institute of Heatly Ageing and Department of Genetics, Evolution and Environment, University College London. Contrary to popular belief, his group proved that sirtuin-2 gene does not expand the lifespan in both worms and flies. This is a very bold claim that goes against a huge wave of scientific research that consistently showed that modulating the levels of sirtuin-2 can reverse the aging process in different animal models.

In 2003, a study also published in Nature showed that increasing the number of copies (1- 3) of sirtuin-2 robustly and significantly increased the lifespan of worms. The story caught the attention of the news media and it revolutionized the field of aging research. Hence, many other research groups started looking at different natural compounds that regulated the activity of sirtuin-2 and suddenly reseveratrol, a component of red wind, was discovered to increase sirtuin activity and extend lifespan. Resveratrol was regarded as the new "fountain of youth" ever since and many natural supplement companies and investors capitalized to spend millions to develop and sell a product that is currently available at the market.

However, Dr. Gem's group claimed the initial observation that sirtuin-2 extends the lifespan in C. elegans (worm model) was flawed since the worm containing the extra copies of sirtuin-2 was compared to a parental wild-type worm that does not have the same genetic background. In other words, the worms containing the sirtuin 2 gene were not backcrossed five generations in order to obtain wild-type worms of the same genetic background. Hence, the right comparisons were never made. The authors of the study also showed that flies that overexpressed sirtuin-2, used in a previously published study, also lived longer compared to the parental wild-type fly strain but did not live longer compared to a fly strain of the same genetic background. These results were independently and blindly repeated by a different research group.

So what caused the worms to live longer in the first study? Interestingly, Dr. Gem's group found that another gene, called "neuronal dye filling defect", but not Sirt-2 was actually the gene responsible for extending lifespan in worms in the 2003 Nature study (go figure). Adding more insult to injury, Dr. Gem's group showed biochemically that resveratrol does not activate sirtuin-2. Interestingly, Dr. Gem's group did not refute the observation that simply increasing the number of sirtuin 2 genes to three copies in worms did efficiently extended the lifespan of worms just expressing one copy of the gene. This observation seems to hold water at least in my view.

Is the science behind sirtuin-2 in peril?

Yes and no. Aging is a very complicated biological process that cannot be explained by a single gene in either worms or flies, let alone in humans. Although today's Nature study damages the view that sirtuin-2 alone can extend lifespan, many other studies in mice and worms have shown that sirtuin-2 can extend the lifespan when interacting with other genes (Daf) and other studies have shown that sirtuin can efficiently regulate insulin growth factor metabolism. Sirtuin-2 may not be a drug target. Moreover, many other studies have shown that resveratrol can be a neuroprotective aging in models of Alzheimer's disease and has been extremely well characterized as an antioxidant. In other words, people will still buy resveratrol based on this other research showing the medical benefits of resveratrol.

Take home message

It is interesting to know that the paper that refutes the work of others which was originally published in Nature gets to be published in the same journal which it is in itself a stunning revelation. So what happened here? It is on the scientist's responsibility to design good hypothesis driven experiments which can lead to publishing false results. However, the reviewers in this case bear the most responsibility for not demanding the appropriate experimental controls from the authors. Ironically, this new study may have revealed another anti-aging gene to pursue: the "dye filling defect"

The controversy will sure go on for many more years...

Although this Examiner article thoroughly reviewed many C. elegans and Drosophila anti-aging studies and makes a scientific argument for both sides of the debate, you can read a sample article published in the media today that somewhat exaggerates the impact of this Nature study.

References:

1.Burnett et al., 2011 Absence of the effects of increasing the expression of Sirt-2 on lifespan of C. elegans and Drosophila. Nature.

2. Tissenbaum, H. A. & Guarente, L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410, 227–230 (2001).

3. Viswanathan, M., Kim, S. K., Berdichevsky, A. & Guarente, L. A role for SIR-2.1 regulation ofERstress response genes in determining C. elegans life span.Dev. Cell 9, 605–615 (2005

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Pain management applications for the iPhone and Android - Pittsburgh Medical Technology | Examiner.com

Although there is a great emphasis in disease prevention and treatment, very little emphasis has been given to pain management and control in the hospital or outside the hospital. Currently, there are over 5820 medical related applications available for free or a small fee for the iPhone and Android phones. Approximately about 111 smartphone applications help to record and manage pain.


What are applications?

Applications are downloadable, highly visual and easy to use programs coded in different languages based on the smartphone's running operating system (OS, UNIX or Windows based). Most applications these days connect to the web and collect information live (GPS, read barcodes, etc..) and are usually available free of charge or for a very small fee (<$15.00 USD).
It is worrisome that there is currently no FDA approval or expert oversight required for the generation and selling of medical related smartphone applications. In addition, only a small fraction of those applications are created by a medical doctor, nurse or healthcare professional which underscores the need to involve the healthcare industry in creating more and robust valuable medical related applications to improve the quality of life.
A study published recently in the Journal of Telemedicine and Telecare carried out a thorough and robust study analyzing the validity, usefulness, and practicality of all pain management applications across all smartphone platforms. Not surprisingly, the authors of the study found that the majority of pain management applications were available for the iPhone (79%), the Android (16%) or Blackberry (5%) while no applications have been created for the Nokia/Symbian or Windows Mobile.
The applications focused on a range of pain categories (acute, chronic, sharp, localized, diffused, low, moderate, high, neuropathic, phantom pain, etc...) and specific health conditions with some overlap and the authors found that approximately 79% of applications were classified as primarily designed to be pain-relevant.
Types of applications
Application sizes ranged from a few kilobytes to a hundreds of megabytes and cost ranged from free to about $10.00 USD. About 24% of all applications have some type of journal component in order to record the localization, type and intensity of pain on a daily basis and how the pain affected daily chores and the quality of life. A few of the applications also emphasized the emotional aspect of pain which usually contributes significantly to pain intensity. In addition to using a pain scale (1 through 10 for most intense), these applications provide emoticons that can be used to describe the emotional component of pain. Over half of the applications included medical and technical related information about pain (symptoms, underlying causes, treatment) and includes a variety of pain reducing or quelling techniques such as massage therapy, and topical treatments. Information about acupuncture and headache prevention were included in a few applications. Only 17% of all applications contain hypnosis and relaxation related techniques as additional tools to help alleviate and quell different types of pain.
These are the most popular pain related applications:
1. Habit changer- It costs $2.00 and maybe a quick and simple e-book for pain management. Habit Changer is a 42 Day Challenge system that helps you kick old habits and experience a new way of living by accessing and heeding a full range of medical related advice. There are no videos and is mostly a text-based application.
2.Pocket Therapy- Costs $4.00. Own a pain management medical encyclopedia with all sorts of factoids! The Pocket Therapy app provides a list of painful injuries. Information on cause, location and symptoms associated with each injury is provided, along with exercises to improve range of motion and strength.
3. Chronic Pain Tracker- The best application with great reviews so far! It is free for the raw/bare version of the application and other modules can be added for a fee. Statistics is the key for making fundamental medical related decisions and the application allows the user to usually highlight the area of the body that is affected by pain on an hourly to daily basis. The application will graph intensity and duration of pain and generate all sorts of quantifiable data that can be analyzed by healthcare professional. It also contains a medication diary that keeps track of the doses and types of medication taken by the patient on a daily basis.
4. My Pain Diary- For a very small price, you can track and record the pain intensity, location, type, trigger, remedy taken and free-text notes. it is a very simple application. Pain intensity is rated on a scale from 0–10 and the data can be relayed to a healthcare professional for further analysis.
5. iPosture- This application tracks the posture and stance of each patient using the iPosture tracking sensor (this device is not free for $70.00 USD). The more the patient crouches or arches the body is related to increased propensity for developing abdominal or back pain. The sensor will alert you through your application of maintaining a correct posture and monitors your balance on a daily basis.