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Potential Lifespan Increasing Substance - Fascinating Investigations
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Current discoveries suggest that the cure for aging is not that far from us. There was a new study recently conducted with a substance normally present in red wine called resveratrol, which proved some fascinating effects of this substance on aging and longevity in preclinical studies on laboratory animals. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a compound of grapes, peanuts and berries. At the moment, the clinical studies of substances with similar mechanism of action are being conducted, and scientists hope to develop useful drugs to treat and prevent common diseases in elderly.

The Role of Sirtuins

There is a big interest among scientists dealing with this problematic for the proteins called sirtuins. Sirtuins are proteins involved in regulation of biological processes in the cells, and, as have been recently discovered, they are very important factors to prevent cell damage due to aging process which keeps the integrity of the tissues, and therefore prevents the development of aging related diseases. The mechanism of action, although not fully described, is focused on mitochondria, the cell organelles responsible for energetic metabolism of the cell. Those organelles seem to age faster than other cell parts, so their preservation and reparation is of the greatest importance when it comes to the aging process.

The Discovery of Resveratrol

It is recently shown that resveratrol has the ability to increase the activity of certain sirtuin called SIRT1. That discovery encouraged the scientists to start the investigation of this substance effects. The experiments have first been conducted on mice, and have shown prolonged lifespan, lower incidence of obesity, an aging related disorders.

"In the history of pharmaceuticals, there has never been a drug that binds to a protein to make it run faster in the way that resveratrol activates SIRT1," said David Sinclair, professor of genetics at Harvard Medical School and senior author on the paper. "Almost all drugs either slow or block them."

Debates About Relevancy of The Results

David Sinclair’s study results were confirmed in many other studies, and all of them proved the relationship between resveratrol and SIRT1. Anyway, there was one thing that bothered skeptic scientists. They were suspicious because SIRT1 protein was studied in vitro, using one chemical group as a fluorescing indicator for increased concentration of SIRT1. Actually, if SIRT1 activity increases, the fluorescing also increases, and that was the way for the detection of resveratol induced increase in SIRT1 activity. This chemical group was artificial, synthetic, and did not exist anywhere in the nature, which guided some scientists to characterize this study as inaccurate or even pure coincidence and experimental artifact.

These happenings were followed by serious debates on the matter, with the central question: Are the effects of resveratrol directly or indirectly affecting the activity of SIRT1? After six years of debate, and serious research, scientists can now tell that the results were definitely not artifacts. "Still, we needed to figure out precisely how resveratrol works. The answer was extremely elegant.", said Sinclair.

Proving The Hypothesis

Sinclair first teamed with other researchers from gonvermental and other institutions to examine the relevancy of his previous results by conducting new research. Their goal was to discover why the cell needs the presence of the chemical group to increase the activity of SIRT1as a response to resveratrol. They surmised that the chemical group was mimicking some other substance already present in the human cell. Only three protein components, amino acids, had a structural similarity with this chemical. The most important of them was tryptophan. So they managed to replace the synthetic chemical group with the residue of tryptophan for the purpose of the new experiment, and as a result, resveratrol again affected the activity of SIRT1 in the sense of increase.

"We discovered a signature for activation that is in fact found in the cell and doesn't require these other synthetic groups," said Hubbard, first author of the study. He also said that this was a critical result, which allowed them to bridge the gap between biochemical and physiological findings.

Further experiments are intended to describe the full process of resveratrol induced activation of SIRT1 on molecular level. For that purpose, scientists have already tested the effects of resveratrol on various mutated forms of SIRT1in order to detect which mutation causes the loss of the effect. Some of them were successful in blocking resveratrol effects. The experiment was confirmed using some newly synthesized chemicals with the same mechanism of action as resveratrol, but much more potent.

So far, there are some assumptions on how resveratrol works, of which the most important is the change of structural organization of SIRT1 induced by resveratrol molecule, followed by increased activation of SIRT1.

First Experiment on a Living Cell

As soon as they succeeded to create mutant genes for SIRT1, scientists were able to conduct the tests on living cells. They have actually replaced the normal gens with mutated, and then compaired the effects of resveratrol on mutated and normal cells. The results were, as expected, very good. Normal cells reacted on resveratrol much stronger than mutated cells by much stronger activation of SIRT1.

"This was the killer experiment," said Sinclair. "There is no rational alternative explanation other than resveratrol directly activates SIRT1 in cells. Now that we know the exact location on SIRT1 where and how resveratrol works, we can engineer even better molecules that more precisely and effectively trigger the effects of resveratrol."

Next Goals

Resveratrol efficiency and safety were already investigated in animal studies, mostly on rats and mice, where its anticancer and antiinflammatory effects were reported. Positive effects on cardiovascular system and decrease in blood sugar concentration were also noted.

Further investigations are most probably headed to the goal of developing drugs and pharmaceuticals with same mechanism of action as resveratrol. Of course, before these drugs become available for use in human medicine, there are a lot of clinical studies to be done in order to investigate their efficiency and safety.

This could not possibly be the drugs that would make us younger, but they most certainly could bring us longer and healthier life, and significant improvement in quality of life.
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