The dose makes the poison: A little bit of resveratrol protects cells from aging

September 26, 2016

Resveratrol, a compound found in red grapes, is famous for its potential health benefits. This positive impact is not due to the antioxidant effect of the substance or the specific activation of certain “aging genes,” as was previously thought. Instead, the substance has a pro-oxidative effect and promotes the formation of free radicals and targeted cell reprogramming to protect against stress. Scientists from the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) and the Max Planck Institute for Molecular Genetics (MPIMG) demonstrated this with experiments on human skin cells.

Dietary supplements with resveratrol, a compound from red grapes, are steadily gaining popularity. Resveratrol has been ascribed almost magical effects, especially on aging, heart disease, and Alzheimer’s. Numerous results of cell experiments and clinical studies could not be reproduced, leaving many questions unanswered.

Dr. Sascha Sauer and his team recently moved from the MPIMG to the Berlin Institute for Medical Systems Biology (BIMSB) at the MDC. Working with scientists in Unilever’s R&D department, they have now found a possible explanation for the mechanisms of action of resveratrol and the contradictory results. Their study was published in the journal Free Radical Biology and Medicine.

Pro-oxidant effect of resveratrol

Sauer’s team recreated conditions inside the body in a test tube, showing that resveratrol had a pro-oxidant rather than an antioxidant effect. “We detected little amounts of reactive oxygen species in the experiment, which caused mild stress in the cells. At the same time, the resveratrol we used decayed rapidly and almost completely,” Sauer explained. “Previous research focused on resveratrol’s potential interactions with certain genes and proteins, and its suspected antioxidant properties.” Antioxidant substances can capture aggressive types of oxygen – free radicals. “Our experiments have shown, however, that small concentrations of resveratrol actually promote the formation of free radicals.”

Tested cells got tougher

Next, the researchers tested the effect of different amounts of resveratrol on cultures of human skin cells, which are also used for testing cosmetics. In small quantities, resveratrol acted as stimulant, training the cells to resist additional oxidative stress and making them more robust than they were before.

Sauer’s team was able to demonstrate this with a series of biochemical control experiments. They also observed that certain genes were specifically activated by resveratrol. This activation resulted in the cells altering their intracellular milieu to an anti-oxidative and “younger” state.

Hormesis – a completely new direction in resveratrol research

The newly discovered mechanism of action has already been on the horizon, according to Sauer, although these findings have largely gone unnoticed. “On closer inspection, the hormesis effect was evident in numerous studies: a positive effect at low doses, but adverse effects at high doses. But nobody noticed it before, because you couldn’t see the underlying mechanism,” says Sauer.

“We hope that our new study will initiate a paradigm shift in resveratrol research. Our results can largely explain the previously established mechanisms of action and resolve many of the current controversies in the pharmacology of resveratrol. They lay the foundations for future targeted research into the substance and its applications. This could also show whether aging processes in the human body can really be delayed by dermatological products or food supplements.”

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This study was funded by the German Federal Ministry of Education and Research (BMBF), the National Genome Research Network (NGFN), the European Union (Seventh Framework Programme), and Unilever R&D.