Resveratrol and sirtuins: to be continued

In search of "eternal life"... and drugs that slow down agingWeekly "Pharmacy"
"Nothing lasts forever under the moon" – scientists of all eras sought to refute this thesis.

Legends about the philosopher's stone and the elixir of youth were replaced by gerontological theories, Faust sold his soul for the secret of immortality, but the fact remained. To find a way to slow down the biological clock counting down the years and to develop drugs that slow down the aging of the body – these are bold tasks that the pharmaceutical industry undertakes to solve. Today, the discussion continues regarding the mechanism of action of resveratrol, a substance that was found in red wine, and its analogues (see the article "La Vie en Rouge"). In this publication, we will tell readers about new achievements in this path.

"You are neither old nor weak. The years have no power over you..."Today, the possibilities of resveratrol, which belongs to the class of biologically active substances – activators of sirtuins (sirtuins; from the English Silent Information Regulator – the regulator of silent information), are being actively studied.

It is assumed that representatives of this class of enzymes regulate the processes of aging, transcription, apoptosis and resistance to stress (for example, starvation) and are responsible for the lifespan of some organisms.

In humans, this enzyme is called SIRT1: in the active state, it cleaves acetyl groups from cellular proteins (including histones – nuclear proteins necessary for the assembly and packaging of DNA strands into chromosomes). This suppresses gene transcription and is presumably the mechanism of its aging-slowing effect.

To evaluate this process, the researchers use an acetylated protein fragment containing a fluorescent label (fluorophore): activated SIRT1 cleaves off the acetyl group, causing a glow. Researchers from Sirtris Pharmaceuticals, a company that the British GlaxoSmithKline acquired in 2008, believe that the greater the fluorescence, the higher the activity of the SIRT1 enzyme.

However, there is also an opposite opinion, according to which resveratrol activates SIRT1 exclusively in the presence of a fluorophore. This conclusion was reached by scientists from the University of Washington in Seattle, as well as researchers from the American biotechnology company Amgen (Kaeberlein M. et al., 2005; Beher D. et al., 2009). This was the fly in the ointment that reduced optimism about the potential effects of resveratrol and its analogues in slowing down the aging process.

Test tube debate

At the same time, it is possible that the conditions "in vitro" cannot fully reflect the complex biochemistry of SIRT1 in living cells. According to the results of a study published in the journal Nature, resveratrol protects rodents from the pathogenic effects of a high-fat diet (Baur J. et al., 2006). In another trial, under the influence of more active resveratrol analogues, insulin sensitivity increased in mice and rats, which opens up prospects for their use in type II diabetes mellitus (Milne J.C. et al., 2007).

The researchers from Sirtris suggest that the substances they have created can form bonds with the fluorophore, however, they admit that this is not the only interaction that increases the activity of SIRT1. Recently, The Journal of Biological Chemistry published the results of a study according to which SIRT1-activating components can interact directly with this enzyme. Thus, the new data will become another argument in the controversy regarding the mechanism of action of substances designed to slow down the aging process.

Portal "Eternal youth" http://vechnayamolodost.ru24.08.2010