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Resvaratrol Mimetics Show Potential as Effective Anti -agjng Drugs

Resvaratrol Mimetics Show Potential as Effective Anti -agjng Drugs

Resveratrol is a polyphenol compound found in the skins of grapes, red wine, peanuts and berries. It gained widespread attention in 2006 when a scientific study suggested that a compound found in small amounts in red wine shows some remarkable anti-aging attributes. It exhibits functions such as increasing cells' sensitivity to insulin, inhjbition of cancer cells and mitigating against the effects of obessity. Resvaratrol already exists in the market as supplements and presently clinical trials are ongoing into developing resveratrol mimetics for prevention and treatment of diseases of aging such as cancer, hearing difficulties and heart diseases.

Resveratrol Mimetics
Resveratrol is easily broken down in the body during first pass metabolism hence it's low bioavailability. For every portion of resveratrol that is consumed, very little of it reaches the desired location where it is to propagate an anti-aging effect. An extremely large amount of it must therefore be consumed before it can have any significant effect. This makes consuming foods containg resveratrol for the purpose of ripping the anti-agjng effect counter productive as consuming excessive amount of such substances can lead to undesired side effects.

Resveratrol mimetics are developed as a way to have a more potent drug which incorporates the part of the resveratrol compound which exhibits the SIRT1 activation property while excluding the part of the compound which gives the undesired side effect when taken at higher dose.

Mechanism
The main agents which acts to mitigate against the effect of aging in humans and other animals are known as sirtuins, one type of sirtuins in particular, SIRT1, acts by boosting the activity of the mitochondria. The mitochondria is the main power house of the cells, it weakens over time and age, the SIRT1 by boosting the mitochondria can help reverse the effect of time on cells leading to better health in old age. This theory has been validated by studies in mice, bees, flies, yeasts and nematodes where extended lifespan was confirmed following SIRT1 activation with resveratrol. The animals were also shown to have significantly increased endurance and immunity to the conditions that come with aging such as heart diseases and obessity.
Resveratrol is a novel and ground breaking drug, to date drugs discovered always come with the adverse effect of blocking or slowing down of other proteins such that as the drug treats one condition, it also causes another to emerge. However in the case of resveratrol the reverse happens. Resveratrol replenishes the protein making it work even better and by so doing prevents the occurence of other diseases.

Research Studies and Clinical Trials
Resveratrol gained attention in 2006 when a Harvard Medical School proffessor, David Sinclair published the results of a study he led in the Journal Science. The study showed that resveratrol extended the lifespan of the model animal used, in this case the model animals were mice. This discovery led to the establishment of a company under GlaxoSmithKlien. The company called Sirtris, is dedicated to the discovery of more potent drugs with resveratol's sirtuin activation characteristics, hence resveratrol mimetics. To date the company has three resveratrol mimetrics in clinical trials.
Previous studies in 2006 pointed out a tendency for direct SIRT1 activation be resveratrol. However the mechanism by which this happens and the validity was not certain until recently in 2013 new findings by the group were able to prove direct SIRT1 activation by resveratrol in animal models as well as validate the mechanism through which this happens.

Understanding and validating the mechanism through which SIRT1 activation by resveratrol occurs is important in the development of drugs which have the same property as resveratrol but with higher potency. These are key aging drugs which have the potential to revolutionalize the concept of aging.

Extensive research have also been done by various other research group on resveratrol. A research study published in the journal Letters of Cancer in 2011 found that resveratrol improves the effectiveness of the anti-cancer drug, rapamycin. In the process of using rapamycin for cancer treatment, the tumour cells may develop a resistance to the drug such that further use no longer has an effect. The study which was carried out by a group of researchers from the Cleveland Clinic Lerner Research Institute found that resveratrol prevents certain breast cancer cells from developing resistance to rapamycin thereby making treatment more effective. Similar findings were made in other studies where results led to the conclusion that resveratrol made cancer cells more vulnerable to chemotherapy and radiotherapy. It does this by increasing the activity of two lethal proteins present in the cancer cells, perforin and granzyme B. When the cells are introduced to resveratrol prior to chemotherapy or radiotherapy, the perforin and granzyme B become highly expressed such that on exposure to radiotherapy or chemotherapy, more of the cancer cells are destroyed. In one study which combined resveratrol and radiotherapy up to 97% of the cancer cells were destroyed which is a high percentage compared to when using radiotherapy alone.

A resveratrol drug , SRT501 was previously produced by Sirtris however the company was recently reported to have terminated clinical trials on this particular drug due to patent and other commercial issues. The company turns focus to three other resveratrol mimetics, SRT1720, SRT2183 and SRT1460 which are presently in clinical trials. Resveratrol capsules and powder forms are presently available in the market as dietery supplements and scientists predict that in the next 5 years or less we should have a clinically tested resveratrol mimetic anti-aging drug in the market.

References
Micheal, P. et al (2010) SRT1720, SRT2183 and SRT1460 are not Direct Activators of SIR1. J. Bio Chem. 285(11): 8340:8351.

Hubbafb, B.P. et al (2013) Evidence for a Common Mechanism of SIRT1 Regulation by Alosteric Activators. Science. 339(6124) 1216-1228.

De Amicis, F.P. (2011) Resveratrol Through NFY/p53/Sin3/HDAC1 Complex Phosphorilation Inhibits Estrogen Receptor Gene Expression via p38MAPK/CK2 in Human Breast Cancer Cell. The FACEB journal 25(10): 3695- 3678.

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